Cancro, la psico-oncologia e la Nuova Medicina Germanica ® di Geerd Ryke Hamer

Psiche e cancerogenesi: le ipotesi e i nessi che si conoscono attualmente in medicina

Natura sanat, medicus curat

Introduzione:

Da molti secoli gira in medicina il sospetto che fattori psicologici, sociali e comportamentali giocherrebbero un possibile ruolo in una eventuale psico-genesi del cancro e per la sopravvivenza di una tale patologia (rif 45 e 51). Il sospetto che traumi psichici potrebbero avere un importanza nella genesi del cancro è radicato in una parte della popolazione, anche se oggi si sa che un tale rapporto è solo debole (vedi rif 6, 15, 17, 18, 59, 102), ma sembra di esistere, almeno per alcune patologie neoplastiche. 40% dei australiani sono convinti che lo stress sarebbe la causa del cancro al seno (rif 51), e nel Canada il 38% delle donne lo pensa (rif 50). Tali supposizioni sono argomenti in TV e in riviste non scientifiche o libri non scientifici. Bisogna distinguere tra una eventuale influenza diretta tra cervello da un lato e un organo bersaglio: lo (dis-)stress, la vita emotiva, possono influenzare lo stato di attivazione del sistema immunitario con consequenze possibili sulla genesi e la crescita tumorale. E dall'altra parte le influenze indirette: la nostra psiche determina le nostre abitudini quotidiane, il consumo di tabacco (essendo cancerogeno), il consumo d'alcool (un fattore di rischio per alcuni tipi di cancro), la dieta (anch' essa gioca un ruolo nella cancerogenesi), il numero delle visite mediche, il numero delle visite mediche di controllo e di previsione, le nostre attività fisiche, la nostra vita sociale, le nostre emozioni cosi via (rif 47). La psiche influenza percio anche le nostre esposizioni verso fattori cancerogeni o fattori protettivi contro il cancro. Cè chi arrabiandosi, o in uno stato di depressione o di disperazione, fuma o beve di piu e influenza cosi il proprio rischio per il cancro. Però: spesso è difficile di distinguere tra le consequenze psichiche della malattia cancro ed il profilo psichologico individuale basale.
Oggi la ricerca si orienta anche ai legami tra psiche e sistema immunitario (e secrezione ormonale), con una probabile importanza per la cancerogenesi e la crescita tumorale da parte del sistema immunitario. Le diffese immunitarie giocano un ruolo determinante nella cancerogenesi (esempio: AIDS/sarcoma di Kaposi o virus HPV) e si sa che uno sforzo psico-sociale influenza paramentri del sistema immunitario, un tipico esempio è il herpes delle labra da HSV-1, che molti conoscono nella fase di preparzione per un esame difficile o in occasiono simili. La psiconeuroimmunologia di oggi non è pero in grado di spiegare in un modo incontestato lo sviluppo di cancro a partire da processi psichici. Non esiste una accetata teoria psicosomatica della cancerogenesi. E non esiste una prova scientifica di una realazione diretta causa-effetto tra sistema immunitario e sviluppo del cancro (rif 126). Le teorie attuali sul cancro si basano su un concetto multifattoriale, anche con fattori psico-sociali di ordine secondario.

A l'inizio del settecento appaiano i primi testi scientifici che tematizzavano il legame tra cancro e lo stress (distress). (rif 1) Nel novecento si pensava che lo stress (nel senso di distress) o ''l'esaurimento nervoso'' sarrebbero eventualmente a l'origine del cancro. Circa 50 anni fa nascevano anzi diverse ipotesi di una particolare "personalità cancrosa'' (personalità a rischio neoplastico), anche denominata del tipo C (typus carcinomatosus o cancer prone), che faciliterebbe l'insorgenza del cancro, un esempio per uno studio che va in questo direzione e il lavoro di Wirsching del 1985 (rif 94). La persona di tipo C sarebbe caratterizzata da una abondante gentilezza, un elevato grado di addatazione sociale, sarebbe spesso depressivo, altruista con tendenza al sacrificarsri, e mostrerebbe una inibizione dell'agressione e una mancante espressività emozionale. Un contributo viene data da Kissen e Eysenck (rif 90) nel 1962 per uomini affetti dal cancro ai polmoni. Una tipologia (6 sub-tipi) particolare veniva sviluppata da Ronald Grossarth-Maticek, filosofo di origine ungarese. Il personaggio carcinomatoso secondo Grossarth-Maticek (tipo 1) sarebbe una persona che si esponesse spesso a sostanze cancerogene, farebbe spesso uso di farmaci, si riposesse poco, eviterebbe conflitti e sarebbe invece particolarmente vulnerabile per offese e eventi traumatici. Le idee di una ''personalita cancrosa'' o tipizzazione psichica del paziente con cancro erano tra di loro contraditori e studi scientifici non hanno potuto dimostrare l'esistenza di un tale personaggio, e di consequenza le corrispondenti ipotesi sono stati abandonati e hanno solo un ruolo storico nella medicina di oggi. (vedi rif 2 e 13). Lavori che contradicono la ipotesi dell'esistenza di una ''personalita cancrosa" sono: (riff 2, 9, 10, 12, 13, 14, 15, 16, 23, 127) Secondo i ricercatori Gruhlke e Faller 1996 (rif 72), le caratteristiche psichologiche attribuite al personaggio ''tipo C'' sono piutosto da considerare la consequenza di una patologia traumatizzante invece di essere alla loro origine.
Nel secolo passato sono stati eleborati in psicologia (psicologia dinamica) anche modelli nevrotici della cancerogenesi (intasamento della libido, cancro come una forma del suicidio voluto, paragoni col parto e cosi via). Esistono anche legami tra alessitimia (incapacita di poter esprimere i propri sentimenti) e le ipotesi di un presunto personaggio cancroso. Un rapporto tra nevroticismo e cancro appare invece nel lavoro di Nakaya (rif 8) nel Giappone, che viene pero contradetto in Danimarca da Hansen (rif 10) nel 2005. Faragher (rif 35) vede nel 1990 un possibile legame tra distress (personaggio tipo A) e cancro al seno. Jasmin, nel 1990 (rif 56) vede nei suoi 77 soggetti una relazione tra prognosi psicosomatica e il rischio per il cancro.
La depressione non sembra facilitare la cancerogensi, potrebbe invece influenzare negativamente la mortalità (Wulsin rif 75 e vedi anche Chorot nel 1994 rif 54). Lo (di-)stress prolungato sembra avere un effetto sulla cangerogenesi (rif 38) nel caso del cancro della cute. Stress chronico sembra pero anche avere un effetto prottetivo nel cancro al seno a causa della sua influenza ormonale (rif 79 e 91).

Nel corso del ultimo ventennio la prospettiva psicosociale in oncologia prende corpo come ambito di studio a sé, anche se sviluppatasi già a partire dagli anni 50 quando, negli Stati Uniti, si costituiscono le prime associazioni di pazienti laringectomizzati, colostomizzati e di donne operate al seno. Presso il Memorial Sloan-Kettering Center di New York nasce in questo periodo il primo Servizio autonomo finalizzato all' assistenza psicologica del paziente affetto da cancro. La psicooncologia vera e propria e nata negli anni 70 e 80 del ultimo secolo. In Italia, le prime tracce risalgono agli anni 70, nel 1980 viene istituito presso l' Istituto nazionale per la ricerca sul cancro di Genova il primo servizio di psicooncologia. Ricercatori prominenti sono per esempio Jimmi Holland (New York).

Il 25-30% delle persone colpite da cancro presenta problemi di ordine emozionale, che nella maggior parte dei casi non vengono colti e presi in giusta considerazione. Circa 20% dei pazienti di cancro mostrano sintomi di una depressione, che spesso non vengono diagnosticati (Secondo Faller). Il psico-oncologo tedesco Volker Tschuschke lo conferma nel suo libro (rif 25). Tali problemi influenzano in maniera negativa la qualità della vita dei pazienti, l'aderenza alla terapie e i rapporti interpersonali. Si possono aggiungere sentimenti di colpa verso la famiglia o altri.

Argomentazione del oncologo italiano Prof U. Veronesi nel 2006 a questo proposito e in relazione alle ipotesi di Geerd Ryke Hamer: Caro (omissis), non conosco il caso di Hamer ma mi fa piacere confrontarmi con lei sulla natura del cancro, anche se non voglio farlo ideologicamente ma scientificamente. Ho già avuto modo di esprimere su questo forum che io credo che tanto il benessere psichico come il suo opposto, la depressione profonda che porta ad una rinuncia alla vita, possono avere un'influenza sulla cura e sulla risposta del malato alla terapia. Sono anche d'accordo con lei che spesso i farmaci anticancro sono poco efficaci, tant'è vero che con il mio team ci stiamo impegnando nella ricerca di nuovi farmaci molecolari meno tossici per l'organismo e nella messa a punto di combinazioni di farmaci tradizionali che permettano l’utilizzo a basse dosi. Tuttavia nella cura del cancro anche il "poco" è importante. Sull'origine psicosomatica del cancro però non abbiamo alcuna evidenza scientifica e dunque, anche se la psicanalisi può sicuramente in alcuni casi far molto bene psicologicamente al paziente, io non mi sentirei mai come medico e come scienziato di considerarla un'alternativa alle cure che, pur con i loro limiti, oggi hanno dimostrato una qualche azione antitumorale. Ciò detto, io sono un gran sostenitore dell'importanza del lato psicologico e soggettivo della malattia, anche e soprattutto quelle più gravi e non mi stanco di ripetere che oggi vale al guarigione ma anche la qualità della guarigione e che la scienza medica non deve mai dimenticare l'attenzione "amorosa" alla persona. (citato da rif 62) Vedi anche rif 125.

maggiori ''life events'' / momenti traumatici: possono scattare il fenomeno cancro ? Smentita della asserzioni rigide di RG Hamer e della ''leggi'' della sua nuova medicina germanica da parte della ricerca internazionale.

L'impatto possibile di cosidetti ''life events'' traumatici (p.e. morte di un familiare/amico nel passato) e specialmente eventi traumatizzant imprevisti come l'attacco allo WTC del 11.9.2001 erano oggetto di ricerca per molti anni (rif 24 e 71) e continua ad essere (rif 119). Sapendo che circa un caso di cancro su 6 è causato da un virus (esempio HPV, HSV, HIV...), la ipotesi immunitaria di life events traumatici sull'insorgenza del cancro appare possibile (attraverso la modulazione del sistema immunitario).

Forsen (rif 5) ha analizzato 87 persone aventi cancro al seno e no (gruppo controllo) per un eventuale rapporto tra eventi traumatici e cancro. Il suo lavoro retrospettivo mostra un numero piu grande di eventi traumatici nel gruppo delle persone con cancro rispetto al gruppo di controllo nei 12 mesi precedenti la diagnosi. Ramirez vede nel 1989 un rapporto tra life events e ricadute nel caso del cancro al seno (rif 19), viene pero smentito da Barraclough (rif 21) nel 1992 e nel 2002 da Graham (rif 20) che aggiunge che donne non dovrebbero avere paura da eventi traumatici come causa di una eventuale ricaduta. Chen (rif 11) trova una relazione tra eventi traumatici e cancro al seno in Cina (in contrasto con Protheroe rif 51). Roberts (rif 4) ha analizzato una eventuale relazione tra ''life events'' e il cancro al seno e nel suo studio con 872 persone nel 1996 non ha potuto trovare una tale relazione e ha trovato stranamente un numero maggiore di persone che hanno perso una persona cara nel gruppo delle donne non aventi cancro. 1999, McKenna trova un rapporto debole tra eventi stressanti e cancro al seno (rif 17). Anche Chorot (rif 54) pensa a una relazione tra psiche e cancro nel 1994. In un review del 2000, Butow vede solo un rapporto debole tra alessitimia, eventi stressanti e cancro (rif 6), con correlazioni positive solo in studi con un numero ristretto di soggetti. L' Australiano Price (rif 7) paragonava nel 2001 donne con processi benigni e donne con malignomi al seno. E dallo suo studio su 514 donne risulta un rapporto positivo da eventi stressanti e malignomi (cancro) in assenza di un aiuto sociale. Questo lavoro contradice invece quello di Maunsell nel 2003 (rif 50) che non trova nessuna prova per una tale asserzione nel caso del cancro al seno, e i lavori di Protheroe del 1999 (rif 51), di Lillberg (nel 2001 rif 52) in Finlandia, e di Duijts (rif 53) in Ollanda lo confermano. Dal review di Dalton (3) del 2002 appare che non si conoscono studi scientifici che mostrano un relazione causale tra ''major life events'' (eventi traumatici), la depressione, o un particolare tipo individuale e il rischio di avere cancro. Dalton afferma che studi scientifici in questo campo contengono spesso un design metodologico debole. Kvikberg, riferisce dalla Norvegia nel 1995 in un indagine su 14231 donne che la morte del marito o il divorzio non modifica il rischio per il cancro, con alcune eccezioni (rif 92), lo stesso autore notera nel anno successivo 1996 nessuna differenza del rischio per cancro in donne che avevano perso un bambino in precedenza (rif 93). Lillberg afferma nel 2003 una relazione positiva tra eventi traumatici e cancro in Finlandia (rif 22), Pereira (USA) afferma che tali eventi sono da considerare fattori di rischio nel 2003 (rif 24) a base di una influenza del sistema immunitario sulle difese del corpo contro virus ongogeni, nello suo studio su pazienti affetti dal HIV.
Il crollo delle due torri dello World Trade Center a New York il 11.9.2001 fu un disastro imprevviso e molto traumatizzante per circa 400.000 persone (con almeno 188 donne incinte nel WTC), 71.000 di queste persone sono elencati nello World Trade Center Health Registry (WTCHR) per una osservazione della loro salute. Secondo le "leggi" della nuova medicina precisamente questo evento avrebbo dovuto scattare molti nuovi casi immediati di cancro, e visto che non si sa niente di una terapia tipo NMG per queste persone non si puo ipottizzare che loro avessero potuto evitare in questo modo lo sviluppo di cancro. Sono stati fatti alcune centinaia di studi dopo il 11-9 e alcune tematizzano un eventuale rapporto tra 11-9 e cancro. La ricerca di Rayne (rif 124) mostra che dopo 4 anni dalla catastrofe, nella zona l'incidenza di cancro era solo leggermente superiore dopo l'attacco rispetto al "fondo", e questo si puo anche spiegare con l'effetto di sostanze cancerogene che furono liberati nelle polveri dissipati durante la catastrofe ed i giorni consecutivi. (furono rilevati nelle polveri composti cancerogeni di idrocarburi policiclici, amianto e cosi via)
E da ricordare pero, che i periodi di latenza tra iniziazione e promozione di tumore e l'apparizione di sintomi puo essere molto lungo. Normalmente si tratta di periodi di latenza 2 a 30 anni (rif 126), in media dura 8 anni. Nel caso di un adulto, e nel caso del mesotelioma puo estendersi fino a 70 anni. I periodi di latenza piu brevi che si conoscono sono periodi di circa due anni nel caso di bambini con una leucemia. Chen riferisce un periodo di cinque anni tra sintomo clinico del cancro al seno e prime modifiche osservabili al microscopio a luce (rif 11), in verità il periodo completo tra inizio e sintomo sara ancora piu lungo. Ma in teoria un effetto psichico potrebbe anche influenzare in senso positivo la crescita di un tumore gia esistente e asintomatico, un contributo per una tale ipotesi danno le osservazioni di Pereira (rif 24) nel caso del carcinoma cervicale nel 2003. In queste condizioni il rapporto temporale potrebbe essere piu breve di 5 anni nel caso di adulti. Eventi traumatici influenzano anche il comportamento: ce chi si cura meno, e evita il contatto con servizi sanitari nel caso di elevato distress, con possibili consequenze sulla patologia stessa. In queste condizioni un intervento professionale puo essere positivo.

In modo riassuntivo: eventi traumatizzanti non sembrano avere una importanza rilevante nella genesi del cancro, vedi conferma nei riferimenti 20, 40 e 73. Risultati da studi fatti all'inzio della psico-oncologia non potevano essere ripetuti e sembrano parzialmente essere ''contaminati'' dalle aspettative dei ricercatori. La ricerca attuale si concentra a partire degli anni 80 di consequenza di piu sulle possibilità di migliorare la qualita di vita (parole riassuntive di Jimmie Holland e Uwe Koch). Da questo punto di vista si spiega la speranza in una nuova psico-oncologia orientata di piu verso quello che si puo fare in pratica per migliorare la qualità di vita dei ammalati di cancro.

fattori neuro-endocrini con una possibile importanza nella cancerogenesi
(l'asse HPA / "asse dello stress")

Psiconeuroimmunologia e cancro, il concetto di ''controllo immunitario del cancro'' di 'Burnets. Tra ormoni coinvolti troviamo: cortisolo, prolatina, melatonina, GH, VIP e la sostanza P. Attualmente si conoscono sopratutto studi fatti su animali, e per l'uomo si conoscono quasi solo correlazioni tra stress e la crescita tumorale, e solo pocchi studi prospettivi.

Le cellule NK (natural killer cells): le cellule NK sono importanti nella difesa del corpo contro il cancro, sopratutto nelle fasi iniziali, ma anche nel caso delle metastasi. Lo stress influenza il numero delle cellule NK circolanti (rif 114), e questo effetto sembra essere sotto controllo ipotalamico. Una stimolazione simpatica determina un abbassamento della concentrazione di cellule NK, betabloccanti possono impedire questo effetto. La morfina (e altri oppioidi) inibisce le cellule NK, d'altro lato si sa che la morfina ha un effetto protettiva nel caso dello stress causato da un intervento chirurugico (rif 115 e 116).

Rapporto tra infiammazioni croniche e cancro: vedi Basak (rif 106).

La communicazione della diagnosi cancro: le consequenze per il paziente

Oggi, al contrario del passato, di solito viene communicata la diagnosi al paziente, anche se una diagnosi infausta puo provocare uno scioc profondo. Nei migliori casi, il paziente viene considerato un partner al quale si communica la verità e non una bugia, perche viene preso al serio. (vedi anche Ipocrate rif 98) Questo perche spesso il paziente ha gia un sospetto da tempo e vuole sapere ''la verità'', e questa sua volonta è da rispettare in una relazione rispettuosa e onesta tra medico e paziente. Ci sono medici che hanno il vizio di mandare prima una infermiera dal paziente mentendo e pretendendo di non conoscere la diagnosi e chiedendolo cosa pensa di avere. Un metodo non compattibile con una relazione onesta tra paziente e terapeuta. Ma, spesso nel inzio del rapporto paziente-medico, quest' ultimo esitera per qualche tempo di communicare i suoi sospetti o anzi i primi risultati di un indagine, si parla nel gergo della "bugie della misericordia". Viene spesso ''concesso'' al paziente di cancro un periodo del ''non-sapere'' che puo creare gravi problemi di onesta nel rapporto e puo avere un effetto molto dannoso per il paziente (rif 97), e che conduce ad una lenta communicazione a diversi passi successivi. Al contrario del passato, le speranze di vita media sono cresciute e in alcuni casi (tumore ai testicoli) questa, dopo una terapia causale, potra essere uguale a quella di persone di stessa età, in altri casi invece la situazione puo essere molto diversa. In Germania, il redditto medio dei medici è in calo rispetto a altri redditti e di consequenza e cambiato anche il rapporto medico-paziente, anche per altri motivi (medicina basata sempre di piu sulle prove e strumenti-apparecchi e meno su interventi suggestivi / cambiamenti politici e sociali) il ruolo del medico e cambiato (forse anche come quello del prete) e questo sta di meno ''sopra'' il paziente. Con la mancanza attuale dei medici (nel 2007 in Germania), la situazione potra cambiare pero.

I pazienti non sono uguali pero: ce chi chiede energicamente di essere informato su tutti i dettagli e dopo una diagnosi molto infausta reagira come un ragioniere organizzando la fine della sua vita scivendo un testamento e cosivia. Altre persone invece chiedono (spesso con un linguagio non-verbale) di non essere informati direttamente a proposito del esito probabile della patologia, e dal medico silenzioso capiscono la diagnosi, o come se questo parlasse in una lingua straniera. Nel silenzio si possono communicare tante verità. Si possono anche vedere diverse reazioni del rinegamento e del rifiuto della diagnosi. Una situazione difficile avviene quando il medico di famiglia ipotizza "qualche infezione" o "tumore benigno" e in un centro specializzato viene diagnosticato il contrario, o se un esamine ha un esito positivo falso.

curando il cancro: interventi psicologici per pazienti e i loro ambiente
le differenti coping style e il loro effetto

La terapia convenzionale del cancro è di solito una terapia con una primaria orientazione somatica. Da partire dalle conoscenze moderne della psico-oncolgia (a partire dalla fine degli anni 70, partendo dagli stati uniti) tale terapia somatica viene piu spesso affiancata da interventi psicologici da psico-oncologi o psicologi con l'intenzione di migliorare la qualita di vita del paziente, ma anche per avere un eventuale effetto possibile sull'esito della patologia. Tutti i grandi centri ospedalieri hanno oggi un servizio psico-onlogico, almeno negli USA.

Esistono molte "coping style": lo "figthing spirit" - il spirito di combattimento da parte del paziente ma anche da parte dell' ambiente. La reazione attiva, orientata alla risoluzione razionale del problema. La reazione della disperazione, del sentimento di essere disarmato, fino al fatalismo e all' aresa. Il rinnegamento, si evita di voler sapere dettagli della proria patologia. La reazione depressiva, la paura in continuazione. La sopressione dei propri emozioni, la alessitemia. Spesso, con l'andamento della malattia, il paziente mostrera reazioni diverse in diversi momenti.

Lavori prospettivi (non retrospettivi) in questo campo: influenza della situatione psicologica sul andamento della patologia:

I lavori di Nielsen e di Kroenke tra l'altro mostrano indipendentemente che elevato stress prolungato e quotidiano potrebbe avere un effetto protettivo contro il cancro al seno nel caso delle donne di età media perche questo gruppo mostra una incidenza minore per questa patologia, forse a causa di una secrezione diversa degli ormoni estrogeni. Qui si possono osservare due fenomeni con un effetto opposto: elevate concentrazione di cortisolo a causa di una attivazione del'asse HPA (con un effetto di promozione per il cancro a causa delle conosciute consequenze per la reattività immunitaria) e l'abassamento contemporale dei ormoni estrogeni con un abassamento del rischio per il cancro al seno e sembra prevalere l'efetto prottetivo su quello di promozione. Stress acuto e stress cronico possono dunque avere effetti diversi sulle probabilità di ammalarsi di cancro.

Relazione tra coping psicologico attivo e periodo di sopravivenza nel cancro del seno:

Si vede che i rapporti positivi si trovano sopratutto nei lavori piu vecchi, la qualità di vita è da distinguere dallo outcome / periodo di sopravivenza.

Dal lavoro di Tschuschke (rif 76): L' impatto dello fighting spirit nel caso della terapia causale della leucemia (adulti) dopo trasplanto del midollo osseo:

Le remissioni spontanee (RS)

Le remissioni spontanee RS sono guarizioni con nessun legame con una precedente terapia causale (rif 34) e che si verificano spontaneamente. La prima RS che e diventata famosa nella storia della medicina è quella di Pellegrino Laziosi di Forli (1265 - 1345 detto anche Pellegrino da Forlì, in inglese Saint Peregrine) che si ammalò di cancro alla tibia e guari completamente senza intervento medico. Pellegrino Laziosi è diventato nel seguito Il Santo protettore degli ammalati di cancro, secondo la fede cattolica.

L' incidenza di una remissione spontanea nel caso di cancro (solo malignomi) è purtroppo un fenomeno molto raro e occorre soltanto una volta su 60000-100000 dei casi (Bashford, Hirschberg). Nel 1992, Stoll (26) ipotizza che in tutto il mondo si possono verificare circa 20 nuovi casi all'anno. In tutta la storia della oncologia si conoscono solo all' incirca 1200 casi corrispondenti e pubblicati in tutto il mondo. Ulrich Abel (biologo e esperto di statistica di Heidelberg) stima che sarebbe molto difficile di stimare le probabilita per una RS. Oggi si sa che le RS possono verificarsi in tutti i tipi di cancro che si conoscono, sono pero piu frequenti nel carcinoma renale, neuroblastoma, melanoma maligno e nel caso dei linfomi e delle leucemie (rif 33 e 63). Le RS sono anche piu frequenti nei bambini. In Germania esistono due gruppi di lavoro che si sono concentrati sulle RS (per esempio Klinikum Nurimberga). Queste remissioni spontanee rarissime non sono inducibili da una terapia conosciuta, anche dal punto di vista della psiconeuroimmunologia moderna. RS sono spesso stati osservati dopo infezioni con elevata febbre (rif 29), e si hanno osservato tempi di maggiore sopravivenza nel caso di una malattia contemporale. Queste osservazioni hanno condotto a tentativi terapeutici immunologici o terapie che inducono la febbre, e hanno stimolato la ricerca dell'ipertermia terapeutica del cancro. (oggi praticamente abbandonata per mancanza di successi, è rimasta in discussione e uso sola la ipertermia locale con-adiuvante e la ricerca continua). Tra i tentativi terapeutici della febbre è da nominare la terapia di Coley con tossine di batteri, ora abbandonata (rif 49) o tentativi terapeutici con una infezione artificiale della malaria. La vaccinazione BCG (Bacille Calmette Guerin), usata nella prevenzione della tuberculosi viene considerata tuttora efficace in modo co-adiuvante in certi tipi di tumori (tumori della vescica urinaria) (rif 67). Studi e meta-analisi retrospettivivi storici delle remissioni spontanee sono quelli di Rohdenburg nel 1918 (rif 64) con 185 casi citati, Fauvet nel 1960/1964 (202 casi), Boyd W (rif 66) nel 1966 (98 casi), Everson e Cole (rif 68) nel 1966 (182 casi), Challis nel 1990 (rif 69 - 489 casi), O'Reagan e Hirschberg nel 1993 (216 casi). Le ricadute dopo una RS sono purtroppo frequenti (rif 49 e 65). Di consequenza occorre aspettare anni dopo una tale remissione per essere sicuro del successo, esattamente come nel caso di una terapia convenzionale del cancro. Il caso del paziente Wright (rif 27) suscitava clamore nel mondo medico: nel suo caso farmaci placebo (causalmente inefficaci) erano efficaci contro linfomi per alcuni mesi, anche se il paziente è decesso dopo la terapia.

Quali possono essere la cause della RS ? Esistono due spiegazioni: le ipotesi somatiche-fisiologiche e le ipotesi psicologiche. Le correlazioni delle RS con malattie infettive danno un contributo alle ipotesi somatiche, anche se non si sa con precisione quale è l'influenza del puro caso. Un contributo alle ipotesi psicologiche danno le osservazioni che lo ''fighting spirit'' (lo spirito di battaglia dello paziente, la "grinta") e un ottimismo e un ottimo sostegno sociale/familiare (con consequenze sulla qualità di vita) avevano un effetto positivo in una minorità degli studi scientifici sulla terapia del cancro - un tale effetto psicologico sembra essere debole, e nella maggioranza degli studi corrispondenti non poteva essere dimostrato o ripetuto, vedi review di Petticrew del 1999 (rif 73) e di Faller nel 2004 (rif 74).

La prevenzione psico-sociale ed ambientale del cancro: esiste un stile di vita che potrebbe essere efficace a diminuire il rischio di riscontrare cancro ?

A scanso dei fattori a rischio ambientali e delle sostanze con conosciuto effetto cancerogeno, fattori psichici come causa di cancro non sembrano invece avere una importanza rilevante. E di consequenza non esiste una "ricetta psicologica" nella prevenzione del cancro. Nell' assistenza psicologica del cancro, la ricerca ''life-event'' da sostegno alla ipotesi che una vita caratterizata da un sufficiente sostegno sociale avrebbero un effetto protettivo nel caso del cancro (rif 44 e 60). Un tale rapporto sociale stabile puo avere un effetto positivo sul sistema immunitario con consequenze sulle difese del corpo contro virus che sono associati a patologie neoplastiche, sapendo che circa il 15% dei tumori sono da vedere in associazione con una infezione virale. Tipici esempi sono il carcinoma cervicale, sarcoma di Kaposi e alcuni tumori del fegato. Pero: una elevata reattività da parte del sistema immunitario, d'altro lato puo avere effetti negativi nel caso di malattie autoimmune come la poliartrite rheumatica. Rafforzare la reattivita immunitaria non è sempre da consigliare. Evidenze che un cambiamento radicale dello stile di vita o il "pensare positivamente" potrebbero curare una patologia neoplastica non esistono.

Conclusione:

Le ipotesi di Ryke Geerd Hamer e della sua nuova medicina germanica ® non sono compattibili con questa revisione della letteratura scientifica fatta a l'inzio del 2007. Hamer sostiene che il cancro, che non suddivide in maligno/benigno, sia il tentativo del cervello di “riparare” (e quindi di guarire) un trauma psicologico inaspettato subito in precedenza. E che basti individuare il trauma sotto acusa e di “disfarlo” (attraverso una cosidetta soluzione) perché il cervello receda dalla sua azione “riparatrice”, arrestando quindi la proliferazione delle cellule neoplastiche una volta per tutte, visto che metastasi non esisterebbero secondo Hamer. Tutto questo ommetendo terapie convenzionali (a parte una minorità degli interventi chirurgici) ed evitando una terapia analgetica effetuata con morfina o farmaci analoghi, esponendo i pazienti a soffererenze in buona parte evitabili con terapie moderne del dolore. Secondo Hamer, una tale sua strada terapeutica avrebbe un successo del 95-98%. Non è in grado pero di dimostrarlo, scusandosi con interventi presunti da parte di loggie massoniche e dalla organizzazione B'nai Brith ebrea e da un complotto da parte della "medicina ufficiale". Dai numerosi lavori elencati non si puo trarre la conclusione certa di una psicogenesi per tutti i tipi di cancro. Una tale psicogenesi sarebbe inoltre non compattibile con i diversi tipi di cancro che hanno una accertata origine virale, origine genetica o una origine dal ambiente (raggi UV / radioattivita naturale) o da sostanze cangerogene (p.e. il fumo / amianto) o da radiazioni ionizzanti man-made. Anche l'esistenza dei tumori trasmissibili (nei animali) non è compattibile con le "leggi" della Nuova Medicina Germanica". Da quello che si sa oggi, processi psichici possono solo avere un ruolo come fattori deboli facilitanti o protettivi, in alcuni estremi rari casi sono forse a l'origine di remissioni spontanee. A l'inzio degli anni 80, a l'epoca della nascita della NMG, la situazione non era cosi chiara come appare oggi. Si sapeva meno, ed erano in discussione modelli di una possibile psicogenesi del cancro. Il diffetto non scusabile di Hamer è da cercare nella sua incapacità di adattare le sue ipotesi-leggi progressivamente a quello che si puo osservare/misurare, di rispondere a nuovi risultati scientifici (anche a risultati deludenti propri), di non basarsi su lavori fatti e pubblicati in precedenza e riferirsi in un modo non-critico a racconti e aneddotti scelti, e di aggrapparsi alle sue leggi, in grande parte scurile. Altri errori non-scusabili (la questione dei artefatti TAC, asserzioni sbagliate nel argomento della lateralita umana e embriologia) si aggiungono a l'odore di antisemitismo (e vicinanza per movimenti di estrema destra come la NPD tedesca) che non è compattibile con un rispetto fermo del essere umano (di ogni razza e confessione) e che deve per forza essere a la base della professione medica pratica. Le sue affermazioni di non essere razzista non convincono un lettore neutrale leggendo le sue lettere pubblicate o interviste, che di piu hanno indotto molti a pensare ad una mania con valore patologico in un uomo invelenito e racchiuso nel suo modo di pensare chiuso ermeticamente dal mondo 'esterno.
L'esito fatale nel caso di numerosi pazienti che hanno creduto in un modo cieco alle promesse del medico o ex-medico charismatico con la sua voce rassicurante-simpatica e che presentavano gravi patologie e la contemporanea mancanza di prove per i presunti successi miracolosi del cancro non lasciano dubbi che la sua strada diagnostica e terapeutica non è idonea per pazienti affetti da una grave patologia.

Pazienti affetti da cancro dovrebbero cercare aiuto competente e professionale e stare lontani dalla terapie della NMG !

La si puo considerare invece come alternativa nel caso di infezioni blandi o disturbi psicosomatici banali, per chi le convinzioni anti-ebrei di Hamer non sono un argomento da stargli lontano.

riferimenti:

(1) LeShan L, psychological states in the development of malignous disease: a critical review. J nat cancer inst 1959:22 1-18

(2) Schwarz R, Die Krebspersönlichkeit, libro: 1994 Schattauer Stuttgard New York.

(3) Dalton SO, Mind and cancer. Do psychological factors cause cancer? in: Eur J Cancer. 2002 Jul;38(10):1313-23
We have reviewed the evidence for an association between major life events, depression and personality factors and the risk for cancer. We identified and included only those prospective or retrospective studies in which the psychological variable was collected independently of the outcome. The evidence failed to support the hypothesis that major life events are a risk factor for cancer. The evidence was inconsistent for both depression and personality factors. Chance, bias or confounding may explain this result, as many of the studies had methodological weaknesses. The generally weak associations found, the inconsistency of the results, the unresolved underlying biological mechanism and equivocal findings of dose-response relationships prevent a conclusion that psychological factors are established risk factors. However, certain intriguing findings warrant further studies, which must, however, be well conducted and large and include detailed information on confounders.

(4) Roberts FD, Self-reported stress and risk of breast cancer, Cancer, 1996 Mar 15;77(6):1089-93
BACKGROUND: Many women attribute the development of their breast cancer to psychosocial factors such as stress and depression. Yet investigations of the relationship between breast cancer and stressful life events have had inconsistent outcomes, due in part to studies with small sample sizes and reliance on hospital-based populations. METHODS: As part of a population-based, case-control study of breast cancer etiology, we evaluated the association between stressful life events and the risk of breast cancer among 258 breast cancer patients and 614 randomly selected population-based controls. Information on 11 stressful life events was collected in telephone interviews with women aged 50-79 who were participating in the ongoing study. RESULTS: Breast cancer patients and controls experienced the same number of stressful life events in the five years prior to diagnosis or an equivalent reference date (controls), averaging 2.4 and 2.6 events, respectively. After adjustment for known breast cancer risk factors, there was no association between weighted stressful life event scores and the risk of breast cancer (odds ratio [OR] = 0.90 per unit increase; 95% confidence interval [CI], 0.78-1.05). Only one life event, death of a close friend, was significantly more often reported by controls (OR = 0.72; 95% CI, 0.52-1.00). Other life events were inconsistently and nonsignificantly associated with breast cancer risk. CONCLUSIONS. The results of this retrospective study do not suggest any important associations between stressful life events and breast cancer risk.

(5) Forsen A, Psychosocial stress as a risk for breast cancer, Psychother Psychosom, 1991;55(2-4):176-85
Life events, important emotional losses, difficult life situations, and psychological characteristics were investigated in a case-control study of 87 breast cancer patients and their controls. In a second part, the effect of stressful life events preceding cancer diagnosis on survival was studied in an 8-year follow-up of the breast cancer group. The control group was selected from the general female population and matched for sex, age, number of child-births, and language. The findings showed that breast cancer patients had significantly more life events, important losses, and difficult life situations prior to the discovery of the breast tumor than controls. The analysis indicated that important losses during a 6-year prodromal period and life event scores prior to examination on both the 12-month and modified 6-year Social Readjustment Rating Scale were associated with subsequent development of breast cancer. The association persisted after adjustment for marital status, education, and social class. The findings of the survival analyses indicated that life events in the 12 months preceding the onset of breast cancer and lower social class were associated with a smaller chance of disease-free and overall survival after controlling for clinical factors.

(6) Butow PN, Epidemiological evidence for a relationship between life events, coping style, and personality factors in the development of breast cancer, J Psychom res, 2000 Sep;49(3):169-81
OBJECTIVE: Review empirical evidence for a relationship between psychosocial factors and breast cancer development. METHODS: Standardised quality assessment criteria were utilised to assess the evidence of psychosocial predictors of breast cancer development in the following domains: (a) stressful life events, (b) coping style, (c) social support, and (d) emotional and personality factors. RESULTS: Few well-designed studies report any association between life events and breast cancer, the exception being two small studies using the Life Events and Difficulties Schedule (LEDS) reporting an association between severely threatening events and breast cancer risk. Seven studies show anger repression or alexithymia are predictors, the strongest evidence suggesting younger women are at increased risk. There is no evidence that social support, chronic anxiety, or depression affects breast cancer development. With the exception of rationality/anti-emotionality, personality factors do not predict breast cancer risk. CONCLUSION: The evidence for a relationship between psychosocial factors and breast cancer is weak. The strongest predictors are emotional repression and severe life events. Future research would benefit from theoretical grounding and greater methodological rigour. Recommendations are given.

(7) Price MA, The role of psychosocial factors in the development of breast carcinoma: Part II. Life event stressors, social support, defense style, and emotional control and their interactions, Cancer, 2001 Feb 15;91(4):686-97
BACKGROUND: The evidence supporting an association between life event stress and breast carcinoma development is inconsistent. METHODS: Five hundred fourteen women requiring biopsy after routine mammographic breast screening were interviewed using the Brown and Harris Life Event and Difficulties Schedule. Other psychosocial variables assessed included social support, emotional control, and defense style. Biopsy results identified 239 women with breast carcinoma and 275 women with benign breast disease. Multiple logistic regression analysis was used to distinguish between breast carcinoma subjects and benign breast disease controls based on these psychosocial variables and their interactions. RESULTS: The findings of the current study revealed a significant interaction between highly threatening life stressors and social support. Women experiencing a stressor objectively rated as highly threatening and who were without intimate emotional social support had a ninefold increase in risk of developing breast carcinoma. CONCLUSIONS: Although there was no evidence of an independent association between life event stress and breast carcinoma, the findings of the current study provided strong evidence that social support interacts with highly threatening life stressors to increase the risk of breast carcinoma significantly.

(8) Nakaya N, Personality traits and cancer survival: a Danish cohort study, Br j cancer, 2006 Jul 17;95(2):146-52. Epub 2006 Jul 4
We conducted a population-based prospective cohort study in Denmark to investigate associations between the personality traits and cancer survival. Between 1976 and 1977, 1020 residents of the Copenhagen County completed a questionnaire eliciting information on personality traits and various health habits. The personality traits extraversion and neuroticism were measured using the short form of the Eysenck Personality Inventory. Follow-up in the Danish Cancer Registry for 1976-2002 revealed 189 incidents of primary cancer and follow-up for death from the date of the cancer diagnosis until 2005 revealed 82 deaths from all-cause in this group. A Cox proportional-hazards model was used to estimate the hazard ratios (HRs) of death from all-cause according to extraversion and neuroticism adjusting for potential confounding factors. A significant association was found between neuroticism and risk of death (HR, 2.3 (95% CI=1.1-4.7); Linear trend P=0.04) but not between extraversion and risk of death (HR, 0.9 (0.4-1.7); Linear trend P=0.34). Similar results were found when using cancer-related death. Stratification by gender revealed a strong positive association between neuroticism and the risk of death among women (Linear trend P=0.03). This study showed that neuroticism is negatively [corrected] associated with cancer survival. Further research on neuroticism and cancer survival is needed.

(9) Nakaya N, Personality and the risk of cancer, j natl cancer inst, 2003 Jun 4;95(11):799-805
http://jnci.oxfordjournals.org/cgi/reprint/95/11/799?ijkey=79f30310e4da10c9c341265b0cecde7e0f4cee4d
BACKGROUND: The role of personality in the causation of cancer has been controversial. We examined this question in a large, prospective study. METHODS: From June through August 1990, 30 277 residents of Miyagi Prefecture in northern Japan completed a Japanese version of the short form of the Eysenck Personality Questionnaire-Revised and a questionnaire on various health habits. There were 671 prevalent cases of cancer at baseline, and 986 incident cases of cancer were identified during 7 years of follow-up, through December 1997. We used Cox proportional hazards regression to estimate the relative risk (RR) of incident cancer (total, stomach, colorectal, breast, and lung) according to four levels of each of four personality subscales (extraversion, neuroticism, psychoticism, and lie), with adjustment for sex, age, education, smoking, alcohol use, body mass index, and family history of cancer. Statistical tests were two-sided. RESULTS: Multivariable RRs of total cancer for individuals in the highest level of each personality subscale as compared with those in the lowest were 0.9 for extraversion (95% confidence interval [CI] = 0.7 to 1.1; P(trend) =.32), 1.1 for psychoticism (95% CI = 0.9 to 1.3; P(trend) =.96), 0.9 for lie (95% CI = 0.7 to 1.0; P(trend) =.19), and 1.2 for neuroticism (95% CI = 1.0 to 1.4; P(trend) =.06). There were no associations between any personality subscale and risk of specific cancers. Neuroticism showed statistically significant positive, linear associations with prevalent cancer at baseline (P(trend)<.001) and with the 320 incident cancer cases diagnosed within the first 3 years of follow-up (P(trend) =.03); however, it showed no association with the 666 cases diagnosed during the fourth through the seventh years of follow-up (P(trend) =.43). CONCLUSION: Our data do not support the hypothesis that personality is a risk factor for cancer incidence. The association between neuroticism and prevalent cancer may be a consequence, rather than a cause, of cancer diagnosis or symptoms.

(10) Hansen PE, Personality traits, health behavior, and risk for cancer: a prospective study of Swedish twin court, Cancer, 2005 Mar 1;103(5):1082-91
BACKGROUND: The authors conducted a prospective investigation into the relation between personality traits and the risk for cancer. METHODS: The study cohort consisted of 29,595 Swedish twins from the national Swedish Twin Registry who were ages 15-48 years at time of entry. In 1973, the twins completed a questionnaire eliciting information on personality traits and health behavior. The Eysenck Personality Inventory was used to measure neuroticism and extroversion as two personality dimensions. A Cox proportional hazards model was used to estimate hazard ratios and 95% confidence intervals for extroversion and neuroticism separately as well as for their joint effect, and conditional logistic regression analyses were conducted to estimate the relation between personality traits and risks for cancer in twin pairs who were discordant for cancer. All analyses were conducted for six etiologically different groups of cancers: hormone-related organ cancers, virus-related and immune-related cancers, digestive organ cancers (excluding liver), respiratory organ cancers, cancers in other sites, and all cancer sites. RESULTS: Follow-up in the Swedish Cancer Registry for 1974-1999 revealed 1898 incidents of primary cancer. The authors found no significant association between neuroticism, extroversion, their joint effects and the risk for any cancer group. CONCLUSIONS: The current results did not support the hypothesis that certain personality traits are associated with cancer risk. 2005 American Cancer Society.

(11) Chen CC, Adverse life events and breast cancer: case-control study, BMJ, 1995 Dec 9;311(7019):1527-30
OBJECTIVE--To investigate the strength of association between past life events and the development of breast cancer. DESIGN--Case-control study. A standardised life events interview and rating was administered before a definitive diagnosis. SETTING--Breast Cancer Screening Assessment Unit and surgical outpatient clinics at King's College Hospital, London. SUBJECTS--119 consecutive women aged 20-70 who were referred for biopsy of a suspicious breast lesion. MAIN OUTCOME MEASURES--Odds ratio of the risk of developing breast cancer after life events in the preceding five years after adjustment for confounders. RESULTS--41 women were diagnosed as having malignant disease while the remainder had benign conditions. Severe life events increased the risk of breast cancer. The crude odds ratio was 3.2 (95% confidence interval 1.35 to 7.6). After adjustment for age and the menopause and other potential confounders this rose to 11.6 (3.1 to 43.7). Multiple logistic regression analysis showed that all severe events and coping with the stress of adverse events by confronting them and focusing on the problems significantly predicted a diagnosis of breast cancer. Non-severe life events and long term difficulties had no significant association. CONCLUSION--These findings suggest an aetiological association between life stress and breast cancer.

(12) Bleiker EM, Personality factors and breast cancer development: a prospective longitudinal study, J natl cancer inst, 1996 Oct 16;88(20):1478-82
http://jnci.oxfordjournals.org/cgi/reprint/88/20/1478?ijkey=ba8a8b7de087a2eb6604b0724ae2f4276bc33545&keytype2=tf_ipsecsha
BACKGROUND: It has been estimated that approximately 25% of all breast cancers in women can be explained by currently recognized somatic (i.e., hereditary and physiologic) risk factors. It has also been hypothesized that psychological factors may play a role in the development of breast cancer. PURPOSE: We investigated the extent to which personality factors, in addition to somatic risk factors, may be associated with the development of primary breast cancer. METHODS: We employed a prospective, longitudinal study design. From 1989 through 1990, a personality questionnaire was sent to all female residents of the Dutch city of Nijmegen who were 43 years of age or older. This questionnaire was sent as part of an invitation to participate in a population-based breast cancer screening program. Women who developed breast cancer among those who returned completed questionnaires were compared with women without such a diagnosis in regard to somatic risk factors and personality traits, including anxiety, anger, depression, rationality, anti-emotionality (i.e., an absence of emotional behavior or a lack of trust in one's own feelings), understanding, optimism, social support, and the expression and control of emotions. Conditional logistic regression analysis was used to identify variables that could best explain group membership (i.e., belonging to the case [breast cancer] or the control [without disease] group). RESULTS: Personality questionnaires were sent to 28 940 women, and 9705 (34%) were returned in such a way that they could be used for statistical analyses. Among the 9705 women who returned useable questionnaires, 131 were diagnosed with breast cancer during the period from 1989 through 1994. Seven hundred seventy-one age-matched control subjects (up to six per case patient) were selected for the analyses. Three variables were found to be statistically significantly associated with an increased risk of breast cancer: 1) having a first-degree family member with breast cancer (versus not having an affected first-degree relative, odds ratio [OR] = 4.05; 95% confidence interval [CI] = 1.76-9.31); 2) nulliparity (i.e., having no children) (versus having had a child before the age of 30 years, OR = 2.67; 95% CI = 1.26-5.68); and 3) a relatively high score on the personality scale of anti-emotionality (versus a low score, OR = 1.19; 95% CI = 1.05-1.35). CONCLUSIONS AND IMPLICATIONS: With the exception of a weak association between a high score on the anti-emotionality scale and the development of breast cancer, no support was found for the hypothesis that personality traits can differentiate between groups of women with and without breast cancer. We recommend that this study be continued and that other studies be encouraged to explore possible relationships between personality factors and the risk of breast cancer.

(13) Sampson W, Controversies in cancer and the mind: effects of psychosocial support, Semin Oncol, 2002 Dec;29(6):595-600
In the last decades of the twentieth century, interest in effects of consciousness on health and illness generated several lines of investigation into effects on cancer. Animal studies showed sensitivity of some cancers to hormonal and stressful influences. However, those findings did not translate into effects on humans, nor did they lead to advances in understanding of human cancer. The proposal that emotional state or stress, mediated through psycho-neuro-immunologic mechanisms would affect cancer generation or growth, resulted in conflicting information. Major surveys found no relationship. The proposal of a cancer personality (Type C) also was not confirmed. Initial observations that depression and stress affected human cancer seem to have best been explained by misinterpretations of cause and effect. By the mid 1990s, a remaining thesis--effect of psychosocial support on longevity and the course of cancer--was yet to be resolved. Initial positive results, especially findings in two popularly quoted studies, were not confirmed; they seem to have been due to inadequate numbers (chance) or to artifacts in study design or implementation. Psychosocial support may result in better adjustment and quality of life, but it does not directly affect the evolution of human cancer.

(14) Schwarz R, Social and psychological differences between cancer and noncancer patients: cause or consequence of the disease? Psychother Psychosom, 1984;41(4):195-9
83 female patients with breast tumors were interviewed prior to biopsy. The interview contained a psychological instrument measuring action control as an indicator for the patients' reaction to stress together with questions about the expected diagnosis. Using multiple-regression analysis we estimated the explained variance of the variables relating to the histological result of the biopsy. Since most of the patients gave a correct prognosis of the nature of their disease-this variable proved to be very important-most of the social psychological findings have to be interpreted as consequences rather than causes of cancer.

(15) Garssen B, Psychological factors and cancer development: evidence after 30 years of research, clin psychol rev, 2004 Jul;24(3):315-38
The question whether psychological factors affect cancer development has intrigued both researchers and patients. This review critically summarizes the findings of studies that have tried to answer this question in the past 30 years. Earlier reviews, including meta-analyses, covered only a limited number of studies, and included studies with a questionable design (group-comparison, cross-sectional or semiprospective design). This review comprises only longitudinal, truly prospective studies (N=70). It was concluded that there is not any psychological factor for which an influence on cancer development has been convincingly demonstrated in a series of studies. Only in terms of 'an influence that cannot be totally dismissed,' some factors emerged as 'most promising': helplessness and repression seemed to contribute to an unfavorable prognosis, while denial/minimizing seemed to be associated with a favorable prognosis. Some, but even less convincing evidence, was found that having experienced loss events, a low level of social support, and chronic depression predict an unfavorable prognosis. The influences of life events (other than loss events), negative emotional states, fighting spirit, stoic acceptance/fatalism, active coping, personality factors, and locus of control are minor or absent. A methodological shortcoming is not to have investigated the interactive effect of psychological factors, demographic, and biomedical risk factors.

(16) Zander E, Cancer--a psychosomatic disease?, Z Psychosom Med Psychoanal, 1983;29(4):363-79
Taking psychoanalytical aspects of psychologically caused symptoms into consideration it is discussed, whether in a narrower sense human cancer can be regarded as a psychosomatic disease or not. Research results in molecular biology including genetics are taken into account. It is held that psychogenesis as a primary cause explains only a minor part of the incidence rate of human cancer. Psychological--or neurotic--influences on the course of the disease are regarded as relatively well proved, but not as specific to cancer. Against hasty psychological explanations of cancer should be warned.

(17) McKenna MC, Psychosocial factors and the development of breast cancer: a meta-analysis, health psychol, 1999 Sep;18(5):520-31
A meta-analysis examined the relationship between psychosocial factors and the development of breast cancer. Average effect sizes (Hedges's g) were calculated from 46 studies for 8 major construct categories: anxiety/depression, childhood family environment, conflict-avoidant personality, denial/repression coping, anger expression, extraversion-introversion, stressful life events, and separation/loss. Significant effect sizes were found for denial/repression coping (g = .38), separation/loss experiences (g = .29), and stressful life events (g = .25). Although conflict-avoidant personality style was also significant (g = .19), the effect size was less robust, and a moderate number of future studies with null results would reduce the significance. Results overall support only a modest association between specific psychosocial factors and breast cancer and are contrary to the conventional wisdom that personality and stress influence the development of breast cancer.

(18) Edwards JR, The relationship between psychosocial factors and breast cancer: some unexpected results, Behav med, 1990 Spring;16(1):5-14
A growing body of research suggests a link between psychosocial factors and breast cancer. Research in this area often contains methodological problems, however, such as small sample size, inadequate comparison groups, omission of important control variables, inclusion of only a few psychosocial variables, and failure to analyze moderating effects. To overcome these problems, the present study examined the link between breast cancer and multiple psychosocial variables (life events, coping, Type A behavior pattern, availability of social support) among 1,052 women with and without breast cancer. After controlling for history of breast cancer and age, we found very few significant relationships between psychosocial variables and breast cancer. Furthermore, the relationship between life events and breast cancer was not moderated by coping, Type A, or availability of social support. Methodological and substantive reasons for these findings are discussed.

(19) Ramirez AJ, Craig TKJ, Watson JP, Fentiman IS, North WRS, Rubens RD. Stress and relapse of breast cancer. BMJ 1989;298:291-3
To elucidate the association between stressful life events and the development of cancer the influence of life stress on relapse in operable breast cancer was examined in matched pairs of women in a case-control study. Adverse life events and difficulties occurring during the postoperative disease free interval were recorded in 50 women who had developed their first recurrence of operable breast cancer and during equivalent follow up times in 50 women with operable breast cancer in remission. The cases and controls were matched for the main physical and pathological factors known to be prognostic in breast cancer and sociodemographic variables that influence the frequency of life events and difficulties. Severely threatening life events and difficulties were significantly associated with the first recurrence of breast cancer. The relative risk of relapse associated with severe life events was 5.67 (95% confidence interval 1.57 to 37.20), and the relative risk associated with severe difficulties was 4.75 (1.58 to 19.20). Life events and difficulties not rated as severe were not related to relapse. Experiencing a non-severe life event was associated with a relative risk of 2.0 (0.62 to 7.47), and experiencing a non-severe difficulty was associated with a relative risk of 1.13 (0.38 to 3.35). These results suggest a prognostic association between severe life stressors and recurrence of breast cancer, but a larger prospective study is needed for confirmation.

(20) Graham J, Stressful life experiences and risk of relapse of breast cancer: observational cohort study, BMJ, 2002 Jun 15;324(7351):1420
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=115851&blobtype=pdf
OBJECTIVE: To confirm, using an observational cohort design, the relation between severely stressful life experiences and relapse of breast cancer found in a previous case-control study. DESIGN: Prospective follow up for five years of a cohort of women newly diagnosed as having breast cancer, collecting data on stressful life experiences, depression, and biological prognostic factors. SETTING: NHS breast clinic, London; 1991-9. PARTICIPANTS: A consecutive series of women aged under 60 newly diagnosed as having a primary operable breast tumour. 202/222 (91%) eligible women participated in the first life experiences interview. 170 (77%) provided complete interview data either up to 5 years after diagnosis or to recurrence. MAIN OUTCOME MEASURE: Recurrence of disease. RESULTS: We controlled for biological prognostic factors (lymph node infiltration and tumour histology), and found no increased risk of recurrence in women who had had one or more severely stressful life experiences in the year before diagnosis compared with women who did not (hazard ratio 1.01, 95% confidence interval 0.58 to 1.74, P=0.99). Women who had had one or more severely stressful life experiences in the 5 years after diagnosis had a lower risk of recurrence (0.52, 0.29 to 0.95, P=0.03) than those who did not. CONCLUSION: These data do not confirm an earlier finding from a case-control study that severely stressful life experiences increase the risk of recurrence of breast cancer. Differences in case control and prospective methods may explain the contradictory results. We took the prospective study as the more robust, and the results suggest that women with breast cancer need not fear that stressful experiences will precipitate the return of their disease.

(21) Barraclough J, Pinder P, Cruddas M, Osmond C, Taylor I, Perry M. Life events and breast cancer prognosis. BMJ 1992;304:1078-81
OBJECTIVE--To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN--Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING--Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS--204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES--Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS--After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION--These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer.

(22) Lillberg K, Stressful life events and risk of breast cancer in 10,808 women: a cohort study, Am j epidemiol, 2003 Mar 1;157(5):415-23
http://aje.oxfordjournals.org/cgi/reprint/157/5/415?ijkey=0b9693306207f4d2e7dd1f46e798450a51bc7ead
The authors prospectively investigated the relation between stressful life events and risk of breast cancer among 10,808 women from the Finnish Twin Cohort. Life events and breast cancer risk factors were assessed by self-administered questionnaire in 1981. A national modification of a standardized life event inventory was used, examining accumulation of life events and individual life events and placing emphasis on the 5 years preceding completion of the questionnaire. Through record linkage with the Finnish Cancer Registry, 180 incident cases of breast cancer were identified in the cohort between 1982 and 1996. The multivariable adjusted hazard ratio for breast cancer per one-event increase in the total number of life events was 1.07 (95% confidence interval (CI): 1.00, 1.15). This risk estimate rose to 1.35 (95% CI: 1.09, 1.67) when only major life events were taken into account. Independently of total life events, divorce/separation (hazard ratio (HR) = 2.26, 95% CI: 1.25, 4.07), death of a husband (HR = 2.00, 95% CI: 1.03, 3.88), and death of a close relative or friend (HR = 1.36, 95% CI: 1.00, 1.86) were all associated with increased risk of breast cancer. The findings suggest a role for life events in breast cancer etiology through hormonal or other mechanisms.

(23) Lillberg K, Personality characteristics and the risk of breast cancer: a prospective cohort study. int j cancer, 2002 Jul 20;100(3):361-6
Various personality characteristics have been suggested to increase the risk of breast cancer but reliable epidemiologic data on this issue are limited. We prospectively investigated the relationship between personality characteristics and the risk of breast cancer in 12,499 Finnish women aged 18 years or more. In health questionnaires in 1975 and 1981, these women completed at least one of the following personality scales: Eysenck extroversion, Bortner type A behaviour and author-constructed measure of hostility. They also reported about other potential breast cancer risk factors. From 1976-1996, 253 cases of breast cancer were identified by record linkage with the Finnish Cancer Registry. Proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). The multivariable HRs of breast cancer for women with intermediate level (scores 3-6) and high level (7-9) of extroversion in 1975 were 1.18 (95% CI 0.87-1.60) and 0.97 (95% CI 0.64-1.47), respectively, compared to those with low level (0-2). These results remained unaltered when the level of extroversion was determined as the average of the 1975 and 1981 reports. There was also no increase in breast cancer risk in relation to type A behaviour and hostility. Furthermore, we observed no substantial joint effects of personality characteristics on the risk of breast cancer. In conclusion, our data do not support the existence of an important role for personality in the aetiology of breast cancer. These findings are reassuring to those who have believed the contrary.

(24) Pereira DB, Life stress and cervical squamous intraepithelial lesions in women with human papillomavirus and human immunodeficiency virus, Psychosom Med, 2003 May-Jun;65(3):427-34
http://www.psychosomaticmedicine.org/cgi/reprint/65/3/427?ijkey=0bd20bb958e7d5a62e1589bb41f88f55d0892e95
OBJECTIVE: Human immunodeficiency virus (HIV)-infected women are at risk for cervical intraepithelial neoplasia (CIN) and cancer due to impaired immunosurveillance over human papillomavirus (HPV) infection. Life stress has been implicated in immune decrements in HIV-infected individuals and therefore may contribute to CIN progression over time. The purpose of this study was to determine whether life stress was associated with progression and/or persistence of squamous intraepithelial lesions (SIL), the cytologic diagnosis conferred by Papanicolaou smear, after 1-year follow-up among women co-infected with HIV and HPV. METHOD: Thirty-two HIV-infected African-American and Caribbean-American women underwent a psychosocial interview, blood draw, colposcopy, and HPV cervical swab at study entry. Using medical chart review, we then abstracted SIL diagnoses at study entry and after 1-year follow-up. RESULTS: Hierarchical logistic regression analysis revealed that higher life stress increased the odds of developing progressive/persistent SIL over 1 year by approximately seven-fold after covarying relevant biological and behavioral control variables. CONCLUSIONS: These findings suggest that life stress may constitute an independent risk factor for SIL progression and/or persistence in HIV-infected women. Stress management interventions may decrease risk for SIL progression/persistence in women living with HIV.

(25) Tschuschke V: Pschoonkologie - Psychologische Aspekte der Entstehung und Bewältigung von Krebs. Stuttgard Schattauer 2002

(26) Stoll BA, Spontaneous regression of cancer: new insights, Biotherapy, 1992;4(1):23-30
Suppression of oncogene expression and of host- or tumour-expressed growth factors and receptors may precipitate spontaneous regression or dormancy in human cancer. Loss of oncogenes necessary for progressive proliferation can lead to differentiation changes. Both natural factors and chemical agents can trigger such a change, and of the naturally occurring agents, growth factors and immunological factors have been most studied. We may find new clues to biological methods of prolonging arrest of cancer, by looking for cytogenetic abnormalities, alterations in oncogene expression and immunocytological composition, in patients showing prolonged dormancy of cancer.

(27) Il caso Wright del 1957: Cancro e l'effetto placebo. "Psychologist Bruno Klopfer was treating a man named Wright who had advanced cancer of the lymph nodes.  All standard treatments had been exhausted and Wright appeared to have little time left.  His neck, armpits, chest, abdomen, and groin were filled with tumors the size of oranges, and his spleen and liver were so enlarged that two quarts of milky fluid had to be drained out of his chest every day. 
Wright heard about an exciting new drug called Krebiozen, and he begged his doctor to let him try it.  At first the doctor refused because the drug was being tried on people with a life expectancy of at least three months.  Finally the doctor gave in and gave Wright an injection of Krebiozen on Friday, but in his heart of hearts he did not expect Wright to last the weekend. "To his surprise, on the following Monday he found Wright out of bed and walking around.  Klopfer reported that his tumors had 'melted like snowballs on a hot stove' and were half their original size.  Ten days after Wright's first treatment, he left the hospital and was, as far as his doctors could tell, cancer free.  When he entered the hospital he had needed an oxygen mask to breathe, but when he left, he was well enough to fly his own plane at 12,000 feet with no discomfort. "Wright remained well for about two months, but then articles began to appear asserting that Krebiozen actually had no effect on cancer of the lymph nodes.  Wright, who was rigidly logical and scientific in his thinking, became very depressed, suffered a relapse, and was readmitted to the hospital.  This time his physician decided to try an experiment.  He told Wright that Krebiozen was every bit as effective as it had seemed, but that some of the initial supplies of the drug had deteriorated during shipping.  He explained, however, that he had a new highly concentrated version of the drug and could treat Wright with this.  The physician used only plain water and went through an elaborate procedure before injecting Wright with the placebo. "Again the results were dramatic.  Tumor masses melted, chest fluid vanished, and Wright was quickly back on his feet and feeling great.  He remained symptom-free for another two months, but then the AMA announced that a nationwide study of Krebiozen had found the drug worthless for the treatment of cancer.  This time Wright's faith was completely shattered.  His cancer blossomed anew and he died two days later."
(Brono Klopfer, Psychological Variables in Human Cancer, Journal of Prospective Techniques 31, 1957, pp. 331-40.)

(27-2) The best known sample of the placebo response, is perhaps the case of Mr Wright, documented in 1957 by Dr Phillip West and Dr Bruno Klopfer. Mr Wright had advanced widespread lymphosarcoma, and as standard treatment has failed, he was expected to live no more than a few weeks. A then new drug (Krebiozen) was being tested as a potential cancer cure, and on Mr Wright`s request, he was included in the trial. Shortly after the first injection of the drug, the patient`s tumor masses “melted like snowballs on a hot stove”. Wright was soon released, apparently free of malignancy. Two months later, shortly after the worthlessness of the drug was being published in newspapers, Mr Wright`s tumours returned. Dr Klopfer, suspecting that this was due to Wright`s expectations, again involved Mr Wright, pretending to give him a double-strength of a new, more active form of the drug, while merely treating him with distilled water. Again the tumours disappeared and Mr Wright was symptom-free for another two months. Then a report from the American Medical Association stating beyond doubt that Krebiozen was worthless, was published in the newspapers. Wright`s tumours reappeared and he died within two days. It is said that it was his total belief in the efficacy of a worthless drug that mobilized a healing placebo response by activating all the major systems of mind-body communication and healing, namely endocrine, autonomic nervous and immune systems.
Riferimenti per questo caso:
http://webspace.quinnipiac.edu/thomas/InformedConsentPlaceboEffectACLMversion2.pdf
Rossi, EL (1986). The psychobiology of mind-body healing. (First edition) WW Norton & Company, Inc.
Watkins, A (1997). Mind-body medicine. A clinicians guide to psychoneuroimmunology. (First edition) Churchill &Livingston.

(28) Sarkar RR, Cancer self remission and tumor stability-- a stochastic approach, Math biosci 2005 Jul, 196 (1) 65
The paper aims to express the spontaneous regression and progression of a malignant tumor system as a prey--predator like system. The model is a three dimensional deterministic system, consisting of tumor cells, hunting predator cells and resting predator cells. Local stability analysis is performed along with numerical simulations to support the analytical findings. Moreover, the deterministic model is extended to a stochastic one allowing random fluctuations around the positive interior equilibrium. The stochastic stability properties of the model are investigated both analytically and numerically. The thresholds obtained from our study may be helpful to control the malignant tumor growth.

(29) Hobohm U, Fever therapy revisited, Br J Cancer 2005 feb 14, 92(3) 421
The phenomenon of spontaneous regression and remission from cancer has been observed by many physicians and was described in hundreds of publications. However, suggestive clues on cause or trigger are sparse and not substantiated by much experimental evidence. In this review, literature is surveyed and summarised and possible causes are discussed. At least in a larger fraction of cases a hefty feverish infection is linked with spontaneous regression in time and is investigated as putative trigger. Epidemiological and immunological evidence is put into perspective.

(30) Bodey B, The spontaneous regression of neoplasms in mammals: possible mechanisms and their application in immunotherapy, In Vivo 1998 Jan-feb 12(1) 107
In mammalian cells, neoplastic transformation is directly associated with the expression of oncogenes, with the mutation, loss or simple inactivation of the function of tumor suppressor genes, and the production of certain growth factors. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various cancers. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in the spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may be neither complete nor permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed.

(31) Horino T, Spontaneous remission of small cell lung cancer: a case report and review in the literature, lung cancer, 2006 Aug;53(2):249-52. Epub 2006 Jun 21
Spontaneous remission (SR) of cancer, especially of lung tumor, is a rare biological event. Only seven cases in which small cell lung cancer (SCLC) regressed spontaneously had been previously reported. We report here a rare case of complete SR of SCLC in an 86-year-old man. Paraneoplastic sensory neuronopathy (PSN) is a rare syndrome, which is associated with malignancy such as SCLC and starts with dysesthetic pain and numbness in the distal extremities, then spreading all four limbs and trunk causing severe sensory ataxia. In the previous reports, SR of SCLC is suggested to result from surgical trauma or PSN, which may be able to enhance anti-tumoral immunity. Our report is the case of SR of SCLC, without any therapies nor any invasive examinations. Although the reason of SR of SCLC in the present case is unknown, PSN could be one of the diagnosis by exclusion.

(32) Horii R, Spontaneous " healing" of breast cancer, Breast cancer, 2005;12(2):140-4
http://www.jstage.jst.go.jp/article/jbcs/12/2/140/_pdf
BACKGROUND: Healing is a phenomenon by which the intraductal component of breast cancer disappears and is replaced by fibrous tissue. Focally localized healing often prevents confirmation of the continuity of intraductal carcinoma. OBJECTIVE: To clarify the clinicopathological characteristics of breast cancer with healing. PATIENTS AND METHODS: At our hospital, 308 patients (311 breasts) underwent breast conservation therapy without neoadjuvant chemotherapy for breast cancer in 2000. These surgical specimens were histopathologically investigated with 5 mm serial sections. We assessed the proportion and the characteristics of breast cancer with healing. RESULTS: (1) The proportion of breast cancer with healing was 7% (21/311). (2) In the 21 patients, the mean age was 59.2 years, and the mean diameter was 2.8 cm. (3) The histological type of the breast cancer varied: noninvasive ductal carcinoma in 2 cases, papillotubular carcinoma in 5, solid-tubular carcinoma in 8, scirrhous carcinoma in 5, invasive lobular carcinoma in 1, and Paget's disease in 1. However in all cases, the histologic type of the intraductal carcinoma foci was the comedo/solid type and the nuclear grade of cancer cells was high. (4) In cases with healing, areas of healing were seen in an average of 5 (1-26) blocks, compared with intraductal carcinoma foci in 13 blocks (2-40). Healing was located on the nipple side of the main lesion in 8 cases, the peripheral side in 9, and both sides in 4. In 3 cases, healing was seen at the surgical margin of the partial mastectomy specimen. CONCLUSION: The proportion of breast cancer cases with healing was 7% and these cases were intraductal carcinoma of the comedo/solid type, consisting of highly malignant cancer cells.

(33) Papac RJ, Spontaneous regression of cancer: possible mechanisms, In Vivo, 1998 Nov-Dec;12(6):571-8
Spontaneous regression of cancer is reported in virtually all types of human cancer, although the greatest number of cases are reported in patients with neuroblastoma, renal cell carcinoma, malignant melanoma and lymhomas/leukemias. Study of patients with these diseases has provided most of the data regarding mechanisms of spontaneous regression. Mechanisms proposed for spontaneous regression of human cancer include: immune mediation, tumor inhibition by growth factors and/or cytokines, induction of differentiation, hormonal mediation, elimination of a carcinogen, tumor necrosis and/or angiogenesis inhibition, psychologic factors, apoptosis and epigenetic mechanisms. Clinical observations and laboratory studies support these concepts to a variable extent. The induction of spontaneous regression may involve multiple mechanisms in some cases although the end result is likely to be either differentiation or cell death. Elucidation of the process of spontaneous regression offers the possibility of improved methods of treating and preventing cancer.

(34) Kaiser HE, Spontaneous neoplastic regression: the significance of apoptosis, In Vivo, 2000 Nov-Dec;14(6):773-88
In mammalian cells, neoplastic transformation has a direct relationship with the expression of oncogenes, the production of certain growth factors and with the mutation, loss or simple inactivation of the function of tumor suppressor genes. Genes for suppression of the development of the malignant immunophenotype, as well as inhibitory growth factors have regulatory functions within the normal processes of cell division and differentiation. Telomerase (a ribonucleoprotein polymerase) activation is frequently observed in various types of neoplastic cell transformation. Telomerase activation is regarded as essential for cell immortalization and its inhibition may result in spontaneous regression (SR) of neoplasms. SR of neoplasms occurs when the malignant tumor mass partially or completely disappears without any treatment or as a result of a therapy considered inadequate to influence systemic neoplastic disease. This definition makes it clear that the term SR applies to neoplasms in which the malignant disease is not necessarily cured, and to cases where the regression may not be complete or permanent. A number of possible mechanisms of SR are reviewed, with the understanding that no single mechanism can completely account for this phenomenon. The application of the newest immunological, molecular biological and genetic insights for more individualized anticancer immunotherapy (biotherapy) is also discussed. In conclusion, of all the possible mechanisms of SR of neoplasms, programmed cell death (PCD) or apoptosis is involved in each. The immunological mechanism is probably the main effector mechanism of SR in human neoplasms with its trigger being apoptosis. The treatments of the tumor, such as with various anti-neoplastic drugs or radiation or immunotherapy, all include the basic mechanism of programmed cell death or apoptosis. Without apoptosis, there is practically no tumor regression, none of any kind.

(35) Faragher EB, Type A stress prone behaviour and breast cancer, Psychol Med, 1990 Aug;20(3):663-70
Department of Medical Statistics, University Hospital of South Manchester, Withington.
This quasi-prospective study of 2163 women attending breast-screening clinics (and controls), indicates that there is a link between personality factors and breast disease. Certain aspects of Type A behaviour seem to be associated with breast-disease states.

(36) Dalton SO, Depression and cancer risk: a register-based study of patients hospitalized with affective disorders, Denmark, 1969-1993, American journal epidem., 2002 Jun 15;155(12):1088-95

(37) Bryla CM, The relationship between stress and the development of breast cancer: a literature review, Oncol Nurs Forum, 1996 Apr;23(3):441-8

(38) Saul AN, Chronic stress and susceptibility to skin cancer, J natl cancer inst, 2005 Dec 7;97(23):1760-7
http://jnci.oxfordjournals.org/cgi/reprint/97/23/1760?ijkey=9c9216b7d06ed0474b50ec0632122cdca08f851f
BACKGROUND: Studies have shown that chronic stress or UV radiation independently suppress immunity. Given their increasing prevalence, it is important to understand whether and how chronic stress and UV radiation may act together to increase susceptibility to disease. Therefore, we investigated potential mediators of a stress-induced increase in emergence and progression of UV-induced squamous cell carcinoma. METHODS: SKH1 mice susceptible to UV-induced tumors were unexposed (naive, n = 4) or exposed (n = 16) to 2240 J/m2 of UVB radiation three times a week for 10 weeks. Half of the UVB-exposed mice were left nonstressed (i.e., they remained in their home cages) and the other half were chronically stressed (i.e., restrained during weeks 4-6). UV-induced tumors were measured weekly from week 11 through week 34, blood was collected at week 34, and tissues were collected at week 35. mRNA expression of interleukin (IL)-12p40, interferon (IFN)-gamma, IL-4, IL-10, CD3epsilon, and CCL27/CTACK, the skin T cell-homing chemokine, in dorsal skin was quantified using real-time polymerase chain reaction. CD4+, CD8+, and CD25+ leukocytes were counted using immunohistochemistry and flow cytometry. All statistical tests were two-sided. RESULTS: Stressed mice had a shorter median time to first tumor (15 versus 16.5 weeks, difference = 1.5 weeks, 95% confidence interval [CI] = -3.0 to 3.3 weeks; P = .03) and reached 50% incidence earlier than controls (15 weeks versus 21 weeks). Stressed mice also had lower IFN-gamma ( mean = 0.03 versus mean = 0.07, difference = 0.04, 95% CI = 0.004 to 0.073; P = .02), CCL27/CTACK (mean = 101 versus mean = 142, difference = 41, 95% CI = 8.1 to 74.4; P = .03), and CD3epsilon (mean = 0.18 versus mean = 0.36, difference = 0.18, 95% CI = 0.06 to 0.30; P = .007) gene expression and lower numbers of infiltrating CD4+ cells (mean = 9.40 versus mean = 13.7, difference = 4.3, 95% CI = 2.36 to 6.32; P = .008) than nonstressed mice. In addition, stressed mice had more regulatory/suppressor CD25+ cells infiltrating tumors and more CD4+ CD25+ cells in circulation (mean = 0.36 versus mean = 0.17, difference = 0.19, 95% CI = 0.005 to 0.38; P = .03) than nonstressed mice. CONCLUSIONS: Chronic stress increased susceptibility to UV-induced squamous cell carcinoma in this mouse model by suppressing type 1 cytokines and protective T cells and increasing regulatory/suppressor T cell numbers.

(39) Baltrusch HJ, Stress, cancer and immunity. New developments in biopsychosocial and psychoneuroimmunologic research, acta neurol (Napoli), 1991 Aug;13(4):315-27

(40) Bleiker EM - van der Ploeg, Psychosocial factors in the etiology of breast cancer: review of a popular link, Pat Educ Couns, 1999 Jul;37(3):201-14
Breast cancer is the most frequently occurring type of cancer in women in the western world. The etiology of a large proportion of breast cancers is still unexplained, and the possibility that psychosocial factors could play a role is not ruled out. Already in pre-Christian times, it was assumed that psychological factors might play a significant role in the development of breast cancer. However, studies have failed to produce conclusive results. There is still a lack of knowledge on the relationship between breast cancer development and psychosocial factors such as stressful life events, coping styles, depression, and the ability to express emotions. The results of this review show that there is not enough evidence that psychosocial factors like 'ways of coping' or 'non-expression of negative emotions', play a significant role in the etiology of breast cancer.

(41) Hilakivi-Clarke L, Psychosocial factors in the development and progression of breast cancer, breast cancer res treat, 1994 Feb;29(2):141-60

(42) Cooper CL, Psychosocial stress and breast cancer: the inter-relationship between stress events, coping strategies and personality, Psychol med 1993 Aug;23(3):653-62

(43) Fox BH, The role of psychological factors in cancer incidence and prognosis, Onclology (Williston Park), 1995 Mar;9(3):245-53

(44) Schüssler G Schubert C, The influence of psychosocial factors on the immune system (psychoneuroimmunology) and their role for the incidence and progression of cancer, Z psychosom Med Psychother, 2001;47(1):6-41
Psychoneuroimmunological research investigates the influence of psychosocial factors on the immune systems. We reviewed clinical studies dealing with the following three topics: life events, psychological/psychopathological factors and social support, and their influence on cellular and humoral immune activity. There is strong evidence that stressful life events (especially losses) have a decreasing effect on immunity. Depression has a similar effect and may be the mediator between life events and the immune systems. Results dealing with the influence of social support on immune functions are still inconclusive. In the second part, we reviewed prospective studies concerning the role of psychosocial factors on cancer incidence and progression. Most of the life event studies reviewed have methodological problems, thus the results are heterogenous. There is some evidence that psychological/psychopathological factors can promote cancer progression. This is even more obvious in case of insufficient social support.

(45) Reynaert C, Psychogenesis" of cancer: between myths, misuses and reality. Bull Cancer, 2000 Sep;87(9):655-64
Summary : Since a long time, hypothesis of links between psychological factors and cancer, have been established in our culture. So far, numerous researches have tempted to indicate stress, coping facing the disease, depression or "type C" personality as factors participating to the onset and/or the course of the cancer. A review of those studies, mainly retrospective, has mostly brought debated results, as well as prospective researches including large sample of population or people awaiting a diagnosis; therefore making oldfashioned every area strictly "psychogenetic" of cancer at first sight. Explicative indirect hypothesis are suggested by the psycho-neuro-endocrino-immunology. Various researches in this field proved that external factors such as stress, depression or social support have significative influences on components of the immune system which in turn influence the onset and/or the course of the cancer. The links between psychological factors and cancer are extremely complex, bringing numerous biological, psychological or even sociological systems in interactions. The psycho-neuro-endocrino-immunology constitutes an early interdisciplinary way of mediation, capable of account for the connections between psychology and cancer.

(46) Jadoulle V, Cancer, a defect of the psyche?, Bull Cancer, 2004 Mar;91(3):249-56

(47) Spiegel D, Kato PM, Psychosocial influences on cancer incidence and progression, Harv rev psychiatry, 1996 May-Jun;4(1):10-26
The impact of psychosocial factors on the incidence and progression of cancer has become an area that demands attention. In this article recent evidence of psychosocial effects on cancer incidence and progression is reviewed in the context of past research. Psychosocial factors discussed include personality, depression, emotional expression, social support, and stress. Mechanisms that could mediate the relationship between psychosocial conditions and cancer incidence and progression are also reviewed. These include alterations in diet, exercise, and circadian cycles; variations in medical treatment received; and physiological mechanisms such as psychoendocrinologic and psychoneuroimmunologic effects. We conclude that there is a nonrandom relationship among various psychosocial factors and cancer incidence and progression that can only partially be explained by behavioral, structural, or biological factors. Suggestions for future research are discussed.

(48) Lambley P, The role of psychological processes in the aetiology and treatment of cervical cancer: a biopsychological perspective, Br J Med Psychol, 1993 Mar;66 ( Pt 1):43-60
Cervical cancer is one of the most serious illnesses affecting women today, particularly in developing societies. Despite medical advances in treatment and the success of cervical screening programmes in detection, the incidence of the disease is increasing. In this paper it is argued that one of the reasons for this is that the aetiological model employed for cervical cancer takes little account of psychological and psychophysiological factors. Both of these factors are now thought to play important roles in disease processes. Research in these areas is reviewed and a new aetiological model for cervical cancer described. This model incorporates existing epidemiological and medical formulations into a new multifactor framework. The implications of this model for treatment are explored and it is suggested that psychological interventions could play a much greater role than they have in the past.

(49) Cann - Van Netten, Dr William Coley and tumour regression: a place in history or in the future, Postgrad Med J, 2003 Dec 79 (938) 672
Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections-no less cancer. Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression. Can it be a coincidence that this method of immunotherapy has been "rediscovered" repeatedly throughout the centuries? Clearly, Coley's approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.

(50) Maunsell E, Stressful life events and survival after breast cancer, Psychosom Med, 2001 Mar-Apr;63(2):306-15
http://www.psychosomaticmedicine.org/cgi/reprint/63/2/306?ijkey=c89eedfd5ea3b5021d6d4b83a3ccfe4539246efa
OBJECTIVE: This study assessed the relation of stressful life events with survival after breast cancer. METHODS: This study was based on women with histologically confirmed, newly diagnosed, localized or regional stage breast cancer first treated in 1 of 11 Quebec City (Canada) hospitals from 1982 through 1984. Among 765 eligible patients, 673 (88%) were interviewed 3 to 6 months after diagnosis about the number and perceived impact of stressful events in the 5 years before diagnosis. Three scores were calculated: number of events; number weighted by reported impact; and for almost 80% of events, number weighted by community-derived values reflecting adjustment required by the event. Scores were divided into quartiles to assess possible dose-response relationships. Survival was assessed in 1993. Hazard ratios and 95% confidence intervals (CIs) comparing all-cause and breast cancer-specific mortality were calculated with adjustment for age, presence of invaded axillary nodes, adjuvant radiotherapy, and systemic therapy (ie, chemotherapy and hormone therapy). RESULTS: When quartiles 2, 3, and 4 were compared with the appropriate lowest quartile, adjusted hazard ratios for all-cause mortality were 0.99 (CI = 0.70-1.38), 0.97 (CI = 0.73-1.31), and 1.04 (CI = 0.78-1.40) for number, number weighted by impact, and number weighted by community-derived values, respectively. Results were essentially similar for the relation between stressful life events limited to those occurring within the 12 months before diagnosis and overall mortality and between stressful life events in the 5 years before diagnosis and breast cancer-specific mortality. CONCLUSIONS: Stress was conceptualized as life events presumed to be negative, undesirable, or to require adjustment by the person confronting them. We found no evidence indicating that this kind of stress during the 5 years before diagnosis negatively affected survival among women with nonmetastatic breast cancer. Evidence from this study and others on the lack of effect of this type of stress on survival may be reassuring for women living with breast cancer.

(51) Protheroe D, Stressful life events and difficulties and onset of breast cancer: case-control study, BMJ, 1999 Oct 16;319(7216):1027-30
OBJECTIVE: To determine the relation between stressful life events and difficulties and the onset of breast cancer. DESIGN: Case-control study. SETTING: 3 NHS breast clinics serving west Leeds. Participants: 399 consecutive women, aged 40-79, attending the breast clinics who were Leeds residents. MAIN OUTCOME MEASURES: Odds ratios of the risk of developing breast cancer after experiencing one or more severe life events, severe difficulties, severe 2 year non-personal health difficulties, or severe 2 year personal health difficulties in the 5 years before clinical presentation. RESULTS: 332 (83%) women participated. Women diagnosed with breast cancer were no more likely to have experienced one or more severe life events (adjusted odds ratio 0.91, 95% confidence interval 0.47 to 1. 81; P=0.79); one or more severe difficulties (0.86, 0.41 to 1.81; P=0.69); a 2 year severe non-personal health difficulty (0.53, 0.12 to 2.31; P=0.4); or a 2 year severe personal health difficulty (2.73, 0.68 to 10.93; P=0.16) than women diagnosed with a benign breast lump. CONCLUSION: These findings do not support the hypothesis that severe life events or difficulties are associated with onset of breast cancer.

(52) Lillberg K, Stress of daily activities and risk of breast cancer: a prospective cohort study in Finland, int j cancer, 2001 Mar 15;91(6):888-93
The belief that life stress enhances breast cancer is common, but there are few prospective epidemiological studies on the relationship of life stress and breast cancer. We have investigated the association between stress of daily activities (SDA) and breast-cancer risk in a prospective cohort study of 10,519 Finnish women aged 18 years or more. SDA measures a subject's own appraisal of daily stress. It was assessed in 1975 and 1981 by a self-administered questionnaire, which also provided information on subject characteristics and other known breast-cancer risk factors. Follow-up data for breast cancer from 1976 to 1996 were attained through record linkage to the Finnish Cancer Registry. Study subjects were divided into 3 groups based on their SDA scores in 1975: no stress (23% of subjects), some stress (68%) and severe stress (9%). Hazard ratios (HRs) and respective 95% confidence intervals (CIs) for incidence of breast cancer by level of SDA were obtained from the Cox proportional hazards model. We identified 205 incident breast cancers in the cohort. Multivariable-adjusted HRs for breast-cancer risk were 1.00 (reference), 1.11 (95% CI 0.78-1.57) and 0.96 (95% CI 0.53-1.73) by increasing level of stress. Neither shifting of the SDA cut-off points nor restricting the analysis to women who reported the same level of SDA in 1975 and 1981 materially altered the results. We found no evidence of an association between self-perceived daily stress and breast-cancer risk.

(53) Duijts SF, The association between stressful life events and breast cancer risk: a meta-analysis, int j cancer, 2003 Dec 20;107(6):1023-9
Breast cancer is the most prevalent cancer in women in Western societies. Studies examining the relationship between stressful life events and breast cancer risk have produced conflicting results. The purpose of this meta-analysis was to identify studies on this relationship, between 1966 and December 2002, to summarize and quantify the association and to explain the inconsistency in previous results. Summary odds ratios and standard errors were calculated, using random effect meta-regression analyses, for the following categories: stressful life events, death of spouse, death of relative or friend, personal health difficulties, nonpersonal health difficulties, change in marital status, change in financial status and change in environmental status. The presence of publication bias has been explored, and sensitivity analyses were performed to identify heterogeneity, using calculation of the percentage of variability due to heterogeneity, meta-regression analyses and stratification. Only the categories stressful life events (OR = 1.77, 95% CI 1.31-2.40), death of spouse (OR = 1.37, 95% CI 1.10-1.71) and death of relative or friend (OR = 1.35, 95% CI 1.09-1.68) showed a statistically significant effect. Publication bias was identified in both stressful life events (p = 0.00) and death of relative or friend (p = 0.02). Sensitivity analyses resulted in the identification of heterogeneity in all categories, except death of spouse. The results of this meta-analysis do not support an overall association between stressful life events and breast cancer risk. Only a modest association could be identified between death of spouse and breast cancer risk. Copyright 2003 Wiley-Liss, Inc.

(54) Chorot P, Life events and stress reactivity as predictors of cancer, coronary heart disease and anxiety disorders, int j psychosom, 1994;41(1-4):34-40
The topic relative to the differential psychobiological mechanisms between cancer and coronary illness has been showing for the last years. In this sense, some theoretical models which have been formulated by relevant authors have suggested the possibility of differentiating cancer and cardiovascular disease, both the onset and the progression, from coping strategies, personality variables and affective states, as well as the different categories of psychosocial stress. Likewise, the implication of psychological distress, such as anxiety, anger and depression for the occurrence of somatic disease has been reported frequently. This research was designed to analyze the psychosocial patterns which could explain the incidence of heart disease, cancer and anxiety based disorders. Measures of life events and stress reactivity were obtained from a total of 109 patients diagnosed as having breast cancer (37), infarct (37), and anxiety (35), and from 72 normal control subjects. Our data tend to show that the cancer group was strongly predicted by lost and illness events, while the coronary group was more associated with work events. The anxiety disorders group lacked a life events dimension, but shared the same category of the infarct group. We also found a strong relationship between depressive reactions and cancer in contrast to the anxiety-anger variable that was more relevant in the infarct patients. The interaction between internal and external stress factors in the etiology of disease is also discussed.

(55) Byrnes DM, Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer, Psychosom Med, 1998 Nov-Dec;60(6):714-22
OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

(56) Jasmin C, Le MG, Marty P, Herzberg R, Psycho-Oncologic between certain psychol Group. Evidence for a linogical factors and the risk of breast cancer in a case control study. Ann Oncol 1990;1:22-9
Unite d'Oncogenese Appliquee, INSERM U 268, Hopital Paul Brousse, Villejuif, France
The relationship between psychosomatic characteristics and the risk of breast cancer was studied in women aged from 35 to 65 years, presenting with a clinically palpable breast tumor. To permit a double-blind design, the psychosomatic evaluation obtained by a long open-ended interview was completed before any diagnostic procedure. On the basis of this evaluation, the psychosomatician concluded that the patient was at high or low risk of serious disease. Several other psychological parameters were also recorded, and the diagnosis was then established by cytology or histology. Nineteen of the 77 patients finally included in the study had histologically verified breast cancer. The relative risk (RR) of breast cancer associated with psychosomatic factors was estimated by multivariate unconditional logistic regression, taking into account age at interview, family history of breast cancer, parity and age at first delivery. A significant relationship (p = 0.02) was found between psychosomatic prognosis and the relative risk of breast cancer. Both the low and high risk groups identified by the psychosomaticians had a similar mean age (46.1 versus 47.6 years). Fundamental mental structure played a predominant role in the risk of breast cancer, since no case was observed among the 18 patients with well organized neurosis, and all the 19 malignant tumors were observed among patients with poorly organized neurosis or psychosis (RR = 7.8, p = 0.009). In addition, excessive self-esteem (RR = 10.0, p = 0.02), hysterical disposition (RR = 7.5, p = 0.02), and unresolved recent grief (RR = 8.2, p = 0.05), were found to be significantly related to the risk of breast cancer....

(57) Scherg H, Psychosocial factors and disease bias in breast cancer patients, Psychosom Ned, 1987 May-Jun;49(3):302-12
The personality patterns of cancer patients as found in retrospective case-control studies are often suspected to be consequences of the disease. In this study an attempt was made to remove the bias arising from the disease itself by taking into account two indicator variables for the subject's anticipation of the subsequently established diagnosis. Seventy-five women with breast cancer were compared to 75 benign controls, matched in pairs for age and "reason for consultation" (the first indicator). Relative risks of 14 psychosocial scales were estimated in turn by logistic regression analysis for matched sets. The analysis showed 13 scales being positively or negatively related to cancer risk in accordance with the hypotheses. After adjusting for "fear of breast cancer" (the second indicator), five scales showed a significant association. In a previous report on this study, neither indicator variable was accounted for and the associations were generally found to be weaker, suggesting that they were masked by the malignant and benign subjects' differences in their degree of anticipation of a cancer diagnosis. As there were no a priori hypotheses regarding these indicator variables, the statistical significance of the results should be treated with caution.

(58) Denz MD, Psychosocial aspects of malignant melanoma, Ther Umschau, 1999 Jun;56(6):342-7
Psychosocial aspects play a role in every stage of malignant melanoma: they are significant in terms of sun exposure habits (primary prevention) and have an important influence on the time lapse between the onset of malignant melanoma and its diagnosis (secondary prevention). Knowledge about psychosocial aspects is also necessary during the course of illness following primary treatment as during this phase patients make critical efforts in understanding and adapting to their illness. These efforts in turn interact with treatment measures and the course of the illness (tertiary prevention). Effective psychosocial interventions are available that can have an important impact on patients' quality of life. Stage-appropriate disease management requires knowledge of relevant psychosocial aspects during the course of cancer and has practical consequences not only for future prevention measures, but also for individual patients, physician-patient relationship and interdisciplinary patient care.

(59) Garssen B, On the role of immunological factors as mediators between psychosocial factors and cancer progression, psychiatry res, 1999 Jan 18;85(1):51-61
Thirty-eight prospective studies on the role of psychological factors in cancer initiation and progression are reviewed. Despite the availability of many prospective studies, there is no certainty about the role of any specific factor. An important reason might be that the interactions among several psychological factors, and the interactions of psychological and biomedical risk factors, have rarely been studied. Some evidence has been found that a low level of social support, a tendency towards helplessness, and repression of negative emotions are factors that promote cancer progression. The effect of psychological factors has been more convincingly demonstrated with respect to cancer progression than cancer initiation, and more convincingly in intervention than in natural history studies. Possible mechanisms mediating associations between psychological factors and disease outcome are discussed. The role of immunosurveillance seems modest overall, and alternative pathways are suggested.

(60) Kiekolt-Glaser JK, Psychoneuroimmunology and cancer: fact or fiction? Eur j cancer, 1999 Oct;35(11):1603-7
There is substantial evidence from both healthy populations as well as individuals with cancer linking psychological stress with immune downregulation. This discussion highlights natural killer (NK) cells, because of the role that they may play in malignant disease. In addition, distress or depression is also associated with two important processes for carcinogenesis: poorer repair of damaged DNA, and alterations in apoptosis. Conversely, the possibility that psychological interventions may enhance immune function and survival among cancer patients clearly merits further exploration, as does the evidence suggesting that social support may be a key psychological mediator. These studies and others suggest that psychological or behavioural factors may influence the incidence or progression of cancer through psychosocial influences on immune function and other physiological pathways.

(61) Goodkin K, Stress and hopelessness in the promotion of cervical intraepithelial neoplasia to invasive squamous cell carcinoma of the cervix, J Pychosom Res, 1986;30(1):67-76
Stress and hopelessness have been associated with the development of invasive cervical cancer by previous research. Subjects in this study were recruited from a colposcopy clinic awaiting work-up of an abnormal pap smear and from those admitted to an in-patient gynecology ward for cone biopsy of the cervix or hysterectomy to treat a symptomatic pelvic mass thought to be uterine leiomyomas. After data collection, pathology reports and colposcopic findings were used to determine group assignment independent of subjects' knowledge of their diagnosis. A modest stress-promotion correlation was derived, which was greatly enhanced by significant interactions with low levels of cooperative coping style and for high levels of premorbid pessimism, future despair, somatic anxiety, and life threat reactivity. These stress-moderator interactions are discussed in terms of immune system deficit with concomitant enhancement of promotion of CIN to invasive squamous cell cervical cancer.

(62) http://www.corriere.it/corrforum/corriere/Thread?forumid=256&postid=480520

(63) Cole WH, Spontaneous regression of cancer and the importance of finding its cause, Natl Cancer Inst Monogr, 1976 Nov, 44
A few years ago Everson and I assembled all the examples of spontaneous regression in the world medical literature from 1900 to 1960 and added numerous cases from expriences of our friends. Our figure was 176. We excluded squamous cell carcinoma of the skin, leukemia, Hodgkin's disease, and a large number of cases that did not fulfill the prerequisites of confirmed diagnosis and no significant treatment. The four most common examples of regression were carcinoma of the kidney (31), neuroblastoma (29), malignant melanoma (19), and choriocarcinoma (19); these constituted more than half the group. We did not require that the regression be permanent because it appeared that the explanation of temporary regression would be just as important as the cause of permanent regression. There was no proven specific cause of the regression, but the following mechanisms had a possible relationship: immunologic action, elimination of carcinogens, trauma (altering the antigen-antibody relationship), hormones, irradiation, infection and/or fever, and drugs or chemicals. The most applicable of these is elimination of the carcinogen. Immunologic reactions seem to offer the best explanation, and the potential of humoral immunity is more impressive than that of cellular immunity.

(64) Rohdenburg, Fluctuations in the growth energy of tumors in man, with esspecial reference to spontaneous recession, 1918 J Cancer Res 1918;3:193-225

(65) Nauts HC, The beneficial effects of bacterial infections on host resistance to cancer, cancer res int 1980

(66) Boyd W. The spontaneous regression of cancer. Charles Thomas, Publ., Springfield Ill. 1966

(67) Cole WH, Relationship of causative factors in spontaneous regression of cancer to immunologic factors possibly effective in cancer, J Surg Oncol, 1976 8 (5) 391
In a book written by Everson and Cole (1966) on spontaneous regression 176 examples of the phenomenon were encountered in the medical literature from 1900 to 1964, supplemented by cases referred by friends. No common denominator of explanations were found. Various types of trauma (e.g., biopsy, incomplete excision), transfusions, infection, hormone changes, drugs, etc. were encountered as possible causative factors. Most significant of all factors was encountered in the 13 examples of spontaneous regression of the bladder; in this series regression of the tumor occurred in 10 after transplantation of the ureters out of the bladder. A consideration and discussion of various reactions in human beings associated with therapeutic regressions have been reviewed hoping to develop a correlation between the two types of regression. At the time of publication of our monograph 9 years ago we were unable to suggest any mechanisms which might explain the regressions. However, since that time so many advances have been made in immunology that it appears now that a stimulation of the immune process might explain most of the regressions. We are just beginning to learn a few methods of stimulating the immune process. Use of BCG is one of the best examples of this stimulating process; other bacterial agents, or fractions, are known to have this action. No doubt there are innumerable others unknown, some of which might explain spontaneous regressions. It would appear that hormonal changes might be responsible for many of the regressions but this author doubts it explains many. More is known at the present time about cellular immunity than humoral immunity, but greater possibilities surely lie in humoral immunity. The blocking and unblocking activities developed by the Hellstroms and associates are no doubt important. Immunoglobulins exert a very important role in the immune process; antibodies may consist of immunoglobulins but much more needs to be known before this relationship can be understood. The recent report (Amery, 1975) that levamisole (given at the time of resection of the lung for carcinoma) improves patient survival is exciting. Amery believes the drug may prevent the hematogenous spread of the tumor during surgery and/or may decrease the immunosuppression caused by a major operation.

(68) Cole WH - Everson TC: Spontaneous Regression of Cancer (WB Saunders, Philadelphia, PA) 1966

(69) Challis GB, The spontaneous regression of cancer. A review of cases from 1900 to 1987, Acta Oncol, 1990 29 (5) 545,
The literature on the spontaneous regression of cancer is reviewed from 1966 to 1987 to update reviews by Everson & Cole and by Boyd. These authors reviewed all cases of spontaneous regression from 1900 to 1965. We then report the entire series from 1900 to 1987. We also attempted to determine what attributions for spontaneous regressions have been reported. Although almost half of the authors failed to speculate or specify a possible cause for the spontaneous regression, the remainder postulated responsible factors such as immunological or endocrine, surgical, necrosis, infection, or operative trauma. The only unorthodox treatment to appear in the literature was the psychological. We conclude that the literature on the spontaneous regression of cancer is still unable to provide unambiguous accounts of the mechanisms operating to affect these regressions.

(70) Shekelle R, Pschological depression and 17-year risk of death from cancer. 1981, Psychosom Med 43 p.117

(71) Antoni MH, Host moderator variables in the promotion of cervical neoplasia--II. Dimensions of life stress, J Psychosom Res, 1989;33(4):457-67
Controllability and predictability have been shown to mediate the aversive impact of life events on health. This study examined the relationship of these parameters (along with coping style) to the promotion of cervical intraepithelial neoplasia (CIN) to invasive squamous cell carcinoma of the cervix. Seventy-five female patients participated while awaiting the results of colposcopically directed biopsy performed during work-up of an abnormal Pap smear. The Million Behavioral Health Inventory, a modified form of the Life Experience Survey, and a semi-structured interview were administered before subjects learned of their biopsy results. Subjects defined as susceptible by previous research had positive (through generally nonsignificant) correlations between life events and promotion while resilient subjects had negative correlations. The relationship between controllability of life events and CIN was moderated beneficially by a sociable and confident style and detrimentally by an inhibited style and a pessimistic attitude. Life event predictability did not contribute to CIN promotion beyond the effects of controllability.

(72) Faller H, cancer personality" attribution--an expression of maladaptive coping with illness?, Z Klin Psychol Psychiatr Psychother, 1996 44(1) 104
In psycho-oncology, the concept of a "cancer-prone personality" has gained some attention. This notion means that persons who try to stay pseudo-normal in spite of severe life stress, suppress negative emotions, particularly anger, and sacrifice themselves for other people without uttering any personal demands, are at a high risk to develop cancer. However, it has been demonstrated by previous research that features of the cancer-prone personality could only be found if the ill person was convinced to suffer from cancer, irrespective of what the factual diagnosis was. Thus it can be concluded that at least some aspects of the so called cancer personality might be the results of coping with the belief of having cancer. The present study had the objective to describe causal attributions to psychosocial factors in cancer patients, and to find out if these were connected with emotional state and coping. N = 120 newly diagnosed lung cancer patients were included in the study. The instruments consisted of a semi-structured interview, a check-list of subjective causal factors, self-reports and interviewer ratings on emotional state and standardised questionnaires about depression and coping. Patients who made a psychosocial causal attribution proved to suffer from greater emotional distress, to be more depressed and less hopeful than other patients. This difference seemed to be mediated by a depressive way of coping with the illness (brooding, wrangling). Thus, an attribution of the illness to psychological factors seems indicative of a maladaptive way of coping with illness. This result is supported by similar findings of previous research. The question is put up to discussion if the psychosomatic concept of a cancer personality may reflect patients' subjective theories which in turn may be the expression of their depressive coping modes.

(73) Petticrew M, Cancer-stress link: the truth, 1999 Nurs Times Mar 3-9 95

(74) Faller H, Prognostic value of depressive coping and depression in survival of lung cancer patients, Psychooncology 2004 May 13 (5) 359
The aim of this investigation was to determine whether depressive coping and depression predict shorter survival among lung cancer patients. We conducted a prospective study using an inception cohort with a 3-5-year follow-up. The sample consisted of n = 59 (of n = 69 invited to participate) patients (mean age 65 years, S.D. = 9.7; 81% male) newly diagnosed with small cell lung cancer or non-small cell lung cancer Stage III or IV who were scheduled for later chemotherapy and/or radiotherapy at a tertiary care centre. Patients were investigated after their diagnosis and before the beginning of treatment. Depressive coping and depression were assessed using standardized self-report questionnaires (Freiburg Questionnaire of Coping with Illness; Hospital Anxiety and Depression Scale). Depressive coping was associated with shorter survival (hazard ratio 1.75, 95% confidence interval 1.04-2.93, p = 0.034) after adjusting for age, sex, stage, histological classification, and Karnofsky performance status but not treatment type, using the Cox proportional hazards regression. Depression, however, was not linked with survival (hazard ratio 1.05, 95% confidence interval 0.98-1.13, p = 0.18). To conclude, the prognostic value of depressive coping was partially confirmed, warranting further examination of the robustness of this relationship.

(75) Wulsin LR, A systematic review of the mortality of depression, Psychosom Med, 1999 Jan 61 (1) 18,
OBJECTIVE: The literature on the mortality of depression was assessed with respect to five issues: 1) strength of evidence for increased mortality, 2) controlling for mediating factors, 3) the contribution of suicide, 4) variation across sample types, and 5) possible mechanisms. METHOD: All relevant English language databases from 1966 to 1996 were searched for reviews and studies that included 1) a formal assessment of depressive symptoms or disorders, 2) death rates or risks, and 3) an appropriate comparison group. RESULTS: There were 57 studies found; 29 (51%) were positive, 13 (23%) negative, and 15 (26%) mixed. Twenty-one studies (37%) ranked among the better studies on the strength of evidence scale used in this study, but there are too few comparable, well-controlled studies to provide a sound estimate of the mortality risk associated with depression. Only six studies controlled for more than one of the four major mediating factors. Suicide accounted for less than 20% of the deaths in psychiatric samples, and less than 1% in medical and community samples. Depression seems to increase the risk of death by cardiovascular disease, especially in men, but depression does not seem to increase the risk of death by cancer. Variability in methods prevents a more rigorous meta-analysis of risk. CONCLUSION: The studies linking depression to early death are poorly controlled, but they suggest that depression substantially increases the risk of death, especially death by unnatural causes and cardiovascular disease. Future well-controlled studies of high risk groups may guide efforts to develop treatments that reduce the mortality risk of depression.

(76) Tschuschke el al, Associations between coping and survival time of adult leukemia patients receiving allogeneic bone marrow transplantation: results of a prospective study, J Psychosom Res 2001 50, 277
BACKGROUND: To investigate associations between coping strategies and length of survival in a sample of 52 adult leukemia patients receiving allogeneic bone marrow transplantation (BMT). METHODS: 52 adult patients, diagnosed with acute (AML) and chronic myeloid leukemia (CML) admitted for allogeneic BMT to a university hospital BMT unit in preparation for a transplantation of genotypically matched HLA donor marrow, were interviewed immediately after informed consent and prior to preparatory treatment for transplantation. Semistructured interviews were conducted and recorded for analysis to assess coping styles and were evaluated by a new content analytic coping measure [Ulm Coping Manual (UCM)]. Patients were a random sample of all eligible patients on the BMT unit between May 1990 and May 1994. RESULTS: Complete audiotaped interviews were rated by blind raters, employing a newly developed content analysis for the identification of patients' coping strategies. Multivariate analysis using a Cox model revealed three pretransplant variables that demonstrated a statistically significant influence on 5-year survival: Stage of Disease at transplant (P < .012), Distraction (P < .007), and Fighting Spirit as coping modalities (P < .013). CONCLUSIONS: The results of this prospective study document the impact of certain psychological variables, notably coping style on survival with BMT. This suggests the necessity of utilizing psychosocial interventions to address stress and anxiety in patients awaiting transplantation in order to reduce anxieties and to employ more effective coping techniques to deal more appropriately with their situation and to enhance Fighting Spirit. The effects on survival of such psychosocial interventions need to be tested in a randomized controlled study.

(77) Faller H, Causal attribution and adaptation among lung cancer patients, J Psychosom Res, 1995 38 (5) 619,
The aim of the present study was to describe lung cancer patients' causal attributions and examine their associations with adaptation. Methods were based on semi-structured interview, content analysis, self-reports, interviewer ratings and standardized questionnaires. 'Smoking cigarettes' and 'toxins in the work place' were the most commonly mentioned possible causes. Patients who made a psychosocial causal attribution suffered greater emotional distress, were more depressed, and less hopeful than other patients. They were also more likely to be rated as showing a maladaptive way of coping with illness. The implications of these findings for psychosocial care are discussed.

(78) Helgesson O, Self-reported stress levels predict subsequent breast cancer in a cohort of Swedish women, Eur J Cancer Prev, 2003 12(5) 377,
The association between stress and breast cancer has been studied, mostly using case-control designs, but rarely examined prospectively. The purpose of this paper is to describe the role of stress as a predictor of subsequent breast cancer. A representative cohort of 1,462 Swedish women aged 38-60 years were followed for 24 years. Stress experience at a baseline examination in 1968-69 was analysed in relation to incidence of breast cancer with proportional hazards regression. Women reporting experience of stress during the five years preceding the first examination displayed a two-fold rate of breast cancer compared with women reporting no stress (age-adjusted relative risk 2.1; 95% CI [1.2-3.7]). This association was independent of potential confounders including reproductive and lifestyle factors. In conclusion, the significant, positive relationship between stress and breast cancer in this prospective study is based on information that is unbiased with respect to knowledge of disease, and can be regarded as more valid than results drawn from case-control studies.

(79) Nielsen NR, Self reported stress and risk of breast cancer: prospective cohort study, BMJ 2005 sept 10 331(7516)
OBJECTIVE: To assess the relation between self reported intensity and frequency of stress and first time incidence of primary breast cancer. DESIGN: Prospective cohort study with 18 years of follow-up. SETTING: Copenhagen City heart study, Denmark. PARTICIPANTS: The 6689 women participating in the Copenhagen City heart study were asked about their perceived level of stress at baseline in 1981-3. These women were followed until 1999 in the Danish nationwide cancer registry, with < 0.1% loss to follow-up. MAIN OUTCOME MEASURE: First time incidence of primary breast cancer. RESULTS: During follow-up 251 women were diagnosed with breast cancer. After adjustment for confounders, women with high levels of stress had a hazard ratio of 0.60 (95% confidence interval 0.37 to 0.97) for breast cancer compared with women with low levels of stress. Furthermore, for each increase in stress level on a six point stress scale an 8% lower risk of primary breast cancer was found (hazard ratio 0.92, 0.85 to 0.99). This association seemed to be stable over time and was particularly pronounced in women receiving hormone therapy. CONCLUSION: High endogenous concentrations of oestrogen are a known risk factor for breast cancer, and impairment of oestrogen synthesis induced by chronic stress may explain a lower incidence of breast cancer in women with high stress. Impairment of normal body function should not, however, be considered a healthy response, and the cumulative health consequences of stress may be disadvantageous.

(80) Greer S, Psychological response to breast cancer: effect on outcome, Lancet 1979 oct 13(2)
A prospective, multidisciplinary, 5-year study of 69 consecutive female patients with early (T0,1N0,1M0) breast cancer was conducted. Patients' psychological responses to the diagnosis of cancer were assessed 3 months postoperatively. These responses were related to outcome 5 years after operation. Recurrence-free survival was significantly common among patients who had initially reacted to cancer by denial or who had a fighting spirit than among patients who had responded with stoic acceptance or feelings of helplessness and hopelessness.

(81) Hislop TG, The prognostic significance of psychosocial factors in women with breast cancer, Chron Dis 1987 40(7) 729,
One hundred and thirty three recently diagnosed breast cancer patients completed a self-administered questionnaire which measured 16 psychosocial variables. After 4 years, three variables (expressive activities at home, extroversion, low anger) were significant prognostic factors for overall survival independent of clinical and other psychosocial factors; likewise three variables (expressive activities at home, expressive activities away from home, low cognitive disturbance) were significant independent prognostic factors for disease-free survival. These findings support the prognostic importance of the social emotional network.

(82) Buddeberg C, Are coping strategies related to disease outcome in early breast cancer? J Psychosom Res 1996 mar 40(3) 255,
A consecutive series of 107 women with early breast cancer were investigated for coping strategies and disease outcome 5 to 6 years after primary surgical treatment (mastectomy or lumpectomy). Coping was assessed several times during a 3-year investigation period by the Zurich and Freiburg Questionnaires of Coping with Illness (ZQCI, FQCI). Data analysis revealed no significant correlations between coping strategies and the target variable "death from breast cancer". However, significant relations were found between postsurgical tumour size (p < or = 0.01), positive histological node status (p < or = 0.01) and death from breast cancer. The results of a discriminant analysis also indicated that somatic parameters are more important for the course of breast cancer disease than psychological aspects of coping. The role of psychosocial variables for the outcome of cancer disease remains unclear and further studies in this field are necessary.

(83) Giraldi T, Psychosocial factors and breast cancer: a 6-year Italian follow-up study, Psychother Psychosom 1997 66(5) 229,
BACKGROUND: Over the last 20 years contradictory results have been obtained as regards to the role of psychosocial factors in favouring the onset of breast cancer and/or in influencing disease progression. METHODS: The present study prospectively investigated the association between psychosocial variables and breast cancer in 95 out-patients. Within 3 months from the diagnosis the patients completed a series of questionnaires to evaluate psychological disturbances, emotional repression, adjustment to cancer, social support and occurrence of life events in the past. At a distance of 6 years from the first assessment, the patients' charts were re-examined in order to evaluate the course of cancer. RESULTS: A higher volume of primary tumour at surgery was shown in patients who had had stressful events in the 6 months preceding cancer diagnosis. At follow-up, no relationship was found between psychosocial variables and the course of disease. The analysis of the frequency of relapses and deaths, and the survival analysis indicated that positivity of loco-regional lymph nodes, infiltrating histotype of the tumour and tumour stage were the only significant predictors of the time of death. CONCLUSIONS: The study suggests that clinical and biological rather than psychosocial factors exert a major role in breast cancer progression.

(84) Watson M, Influence of psychological response on survival in breast cancer: a population-based cohort study, Lancet, 1999 Oct 16;354(9187):1331-6, BACKGROUND: The psychological response to breast cancer, such as a fighting spirit or an attitude of helplessness and hopelessness toward the disease, has been suggested as a prognostic factor with an influence on survival. We have investigated the effect of psychological response on disease outcome in a large cohort of women with early-stage breast cancer. METHODS: 578 women with early-stage breast cancer were enrolled in a prospective survival study. Psychological response was measured by the mental adjustment to cancer (MAC) scale, the Courtauld emotional control (CEC) scale, and the hospital anxiety and depression (HAD) scale 4-12 weeks and 12 months after diagnosis. The women were followed up for at least 5 years. Cox's proportional-hazards regression was used to obtain the hazard ratios for the measures of psychological response, with adjustment for known clinical factors associated with survival. FINDINGS: At 5 years, 395 women were alive and without relapse, 50 were alive with relapse, and 133 had died. There was a significantly increased risk of death from all causes by 5 years in women with a high score on the HAD scale category of depression (hazard ratio 3.59 [95% CI 1.39-9.24]). There was a significantly increased risk of relapse or death at 5 years in women with high scores on the helplessness and hopelessness category of the MAC scale compared with those with a low score in this category (1.55 [1.07-2.25]). There were no significant results found for the category of "fighting spirit". INTERPRETATION: For 5-year event-free survival a high helplessness/hopelessness score has a moderate but detrimental effect. A high score for depression is linked to a significantly reduced chance of survival; however, this result is based on a small number of patients and should be interpreted with caution.

(85) Reynolds P, Use of coping strategies and breast cancer survival: results from the Black/White Cancer Survival Study, Am J Epidemiol 2000 nov 15 152(10) 940,
This analysis was designed to evaluate the association between coping strategies and breast cancer survival among Black and White women in a large population-based study. A total of 442 Black and 405 White US women diagnosed with invasive breast cancer during 1985-1986 and actively followed for survival through 1994 were administered a modified Folkman and Lazarus Ways of Coping questionnaire. Coping strategies were characterized via factor analyses of the responses. Hazard ratios associated with coping strategies were estimated using Cox proportional hazards models, with adjustment for age, race, tumor stage, study location, tumor hormone responsiveness, comorbidity, health insurance status, smoking, relative body weight, and alcohol consumption. Emotion-focused coping strategies were significantly associated with survival. Expression of emotion was associated with better survival (hazard ratio = 0.6; 95% confidence interval: 0.4, 0.9). When it was considered jointly with the presence or absence of perceived emotional support, women reporting low levels of both emotional expression and perceived emotional support experienced poorer survival than women reporting high levels of both (hazard ratio = 2.5; 95% confidence interval: 1.7, 3.7). Similar risk relations were evident for Blacks and Whites and for patients with early and late stage disease. These results suggest that the opportunity for emotional expression may help improve survival among patients with invasive breast cancer.

(86) Goodwin PJ, The effect of group psychosocial support on survival in metastatic breast cancer, NEJM, 2001 Dec 13;345(24):1719-26
BACKGROUND: Supportive-expressive group therapy has been reported to prolong survival among women with metastatic breast cancer. However, in recent studies, various psychosocial interventions have not prolonged survival. METHODS: In a multicenter trial, we randomly assigned 235 women with metastatic breast cancer who were expected to survive at least three months in a 2:1 ratio to an intervention group that participated in weekly supportive-expressive group therapy (158 women) or to a control group that received no such intervention (77 women). All the women received educational materials and any medical or psychosocial care that was deemed necessary. The primary outcome was survival; psychosocial function was assessed by self-reported questionnaires. RESULTS: Women assigned to supportive-expressive therapy had greater improvement in psychological symptoms and reported less pain (P=0.04) than women in the control group. A significant interaction of treatment-group assignment with base-line psychological score was found (P</=0.003 for the comparison of mood variables; P=0.04 for the comparison of pain); women who were more distressed benefited, whereas those who were less distressed did not. The psychological intervention did not prolong survival (median survival, 17.9 months in the intervention group and 17.6 months in the control group; hazard ratio for death according to the univariate analysis, 1.06 [95 percent confidence interval, 0.78 to 1.45]; hazard ratio according to the multivariate analysis, 1.23 [95 percent confidence interval, 0.88 to 1.72]). CONCLUSIONS: Supportive-expressive group therapy does not prolong survival in women with metastatic breast cancer. It improves mood and the perception of pain, particularly in women who are initially more distressed.

(87) Goodwin PJ, Health-related quality of life and psychosocial status in breast cancer prognosis: analysis of multiple variables, J Clin Oncol 2004 oct 15 22(20),
PURPOSE: Evidence that psychosocial status and health-related quality of life (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent. We examined prognostic effects of these factors in a prospective cohort study. PATIENTS AND METHODS: Three hundred ninety-seven women with surgically resected T1 to T3, N0/N1, M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale, Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records, and Cox survival analyses were performed. RESULTS: Mean age was 52.0 +/- 9.9 years. Two hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women had TX tumors; 127 were N1. One hundred thirteen women received adjuvant chemotherapy, 130 received hormone therapy, 45 received both, and 109 received neither. We investigated 140 prognostic associations; four were found to be statistically significant at a P value of </= .05 (three fewer than expected by chance). Two were in the hypothesized direction of effect, and two were in the opposite direction. All arose from measurements 1 year after diagnosis, which were most susceptible to confounding by treatment. There was no evidence of consistency of associations across outcomes or questionnaires. These results are in keeping with chance as the explanation for our statistically significant findings. CONCLUSION: HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC.

(88) Spiegel D, Effect of psychosocial treatment on survival of patients with metastatic breast cancer, Lancet, 1989 Oct 14;2(8668):888-91
The effect of psychosocial intervention on time of survival of 86 patients with metastatic breast cancer was studied prospectively. The 1 year intervention consisted of weekly supportive group therapy with self-hypnosis for pain. Both the treatment (n = 50) and control groups (n = 36) had routine oncological care. At 10 year follow-up, only 3 of the patients were alive, and death records were obtained for the other 83. Survival from time of randomisation and onset of intervention was a mean 36.6 (SD 37.6) months in the intervention group compared with 18.9 (10.8) months in the control group, a significant difference. Survival plots indicated that divergence in survival began at 20 months after entry, or 8 months after intervention ended.

(90) Kissen DM Eysenck HJ, Personality in male lung cancer patients, J Psychosom Res, 1962 apr-june 6 123

(91) Kroenke CH, Caregiving stress, endogenous sex steroid hormone levels, and breast cancer incidence, Am J Epidemiol 2004 june 1 159(11) 1019,
Stress is hypothesized to be a risk factor for breast cancer. The authors examined associations of hours of, and self-reported levels of stress from, informal caregiving with prospective breast cancer incidence. Cross-sectional analyses of caregiving and endogenous sex steroid hormones were also conducted. In 1992 or 1996, 69,886 US women from the Nurses' Health Study, aged 46-71 years at baseline, answered questions on informal caregiving; 1,700 incident breast cancer cases accrued over follow-up to 2000. A subset of 665 postmenopausal women not taking exogenous hormones returned a blood sample in 1990. Numbers of hours of care provided to an ill adult or to a child were each summed and analyzed as 0 (reference), 1-14, and >/=15 per week. Cox proportional hazards models were used in prospective analyses and linear models in cross-sectional analyses. High numbers of caregiving hours and self-reported stress did not predict a higher incidence of breast cancer. However, compared with women providing no adult care, women providing >/=15 hours of adult care (median, 54) had significantly lower levels of estradiol (geometric mean, 9.21 pg/ml vs. 7.46 pg/ml (95% confidence interval: 6.36, 8.76)) and bioavailable estradiol (geometric mean, 1.86 pg/ml vs. 1.35 pg/ml (95% confidence interval: 1.00, 1.82)). Stress from caregiving did not appear to increase breast cancer risk.

(92) Kvikstad A, Widowhood and divorce in relation to overall survival among middle-aged Norwegian women with cancer, Br J Cancer 1995 june 71(6) 1343,
The aim of the study was to examine the relations between widowhood and divorce and overall survival among women with cancer. All Norwegian women born between 1935 and 1954, and diagnosed with cancer between 1966 and 1990, were followed up until 1991. In all, 14,231 cases were followed up for a median length of approximately 4.5 years (mean = 6 years), and 4311 women died during follow-up. In addition to overall cancer, separate analyses have been made for cancer at specific sites. Widows had a risk of dying which was nearly identical to that of married women for all sites except colorectal cancer, for which widows had a 2-fold increased death rate compared with married women. Divorced women had an overall increased hazard ratio of 1.17 (95% CI 1.07-1.27), which was confined to cancer of the breast, lung and cervix. With few clear exceptions women with children had a better survival than nulliparous women (overall hazard ratio = 0.80, 95% CI 0.74-0.87).

(93) Kvikstad A, Risk and prognosis of cancer in middle-aged women who have experienced the death of a child. Int J Cancer, 1996 july 17 67(2) 165,
First, we studied the relative risk of cancer among women born between 1935 and 1954 who had experienced a child's death, compared with women without this experience. Second, we examined whether survival was any different between cancer patients in the 2 groups. The study was a population-based nested case-control study that included 14,669 cancer cases and 29,750 age-matched controls. The women who were included as incident cases were further analyzed using Cox regression in a study of total survival. The overall relative risk of cancer among women who had lost a child was nearly identical to that of women who had not lost a child (OR = 0.96, 95% confidence interval 0.87-1.07), after adjustment for age and parity. In the analysis of specific cancer sites, there was no difference in relative risk between the 2 groups. In relation to cancer survival, we found that patients who had lost a child had an overall risk of dying that was nearly identical to patients who had not had this experience (HR = 1.08, 95% confidence interval 0.92-1.26), after adjustment for age and stage at diagnosis. For specific sites of cancer, the results also showed no difference in survival between the 2 groups. In conclusion, risk and survival of cancer were not different among women who had experienced the death of a child from the risk and survival among women without this experience.

(94) Wirsching M, Prebioptic psychological characteristics of breast cancer patients, Psychother Psychosom, 1985 43(2) 69-76, 63 women were examined the day before breast biopsy using psychological ratings, speech analysis and questionnaire testings. Ratings revealed differences (benign vs. malignant, a = 5%) in 8 of 10 scales, cancer patients being inaccessible, altruistic, suppressing feelings, rationalizing and harmonizing. The biopsy's result was predicted in 75% of all cases. Questionnaire testing showed differences in 7 of 16 scales. It proved cancer patients to be more dependent, anxious, aggressive, health-conscious, family-bound and antisexual. A discriminant analysis correctly identified 77% of cancer and 87% of benign patients. Speech analysis (Gottschalk-Gleser) revealed only minor differences: fewer aggressive and more anxious utterances from cancer patients. Conclusions are drawn for the care and treatment of breast cancer patients.

(95) Shrock D, Effects of a psychosocial intervention on survival among patients with stage I breast and prostate cancer: a matched case-control study, Altern Ther Health Med, 1999 May;5(3):49-55
CONTEXT: Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. OBJECTIVE: To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. DESIGN: Matched case-control. SETTING: 3 rural hospitals or cancer centers in central Pennsylvania. PATIENTS: 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). INTERVENTION: Six 2-hour health psychology classes conducted by a licensed staff psychologist. MAIN OUTCOME MEASURES: Survival time was compared between the 2 groups and with national norms. RESULTS: The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. CONCLUSIONS: These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.

(96) Greer S, Adjuvant psychological therapy for patients with cancer: a prospective randomised trial, BMJ, 1992 Mar 14;304(6828):675-80
OBJECTIVE--To determine the effect of adjuvant psychological therapy on the quality of life of patients with cancer. DESIGN--Prospective randomised controlled trial comparing the quality of life of patients receiving psychological therapy with that of patients receiving no therapy, measured before therapy, at eight weeks, and at four months of follow up. SETTING--CRC Psychological Medicine Group of Royal Marsden Hospital. PATIENTS--174 patients aged 18-74 attending hospital with a confirmed diagnosis of malignant disease, a life expectancy of at least 12 months, or scores on various measures of psychological morbidity above previously defined cut off points. INTERVENTION--Adjuvant psychological therapy, a brief, problem focused, cognitive-behavioural treatment programme specifically designed for the needs of individual cancer patients. MAIN OUTCOME MEASURES--Hospital anxiety and depression scale, mental adjustment to cancer scale, Rotterdam symptom checklist, psychosocial adjustment to illness scale. RESULTS--156 (90%) patients completed the eight week trial; follow up data at four months were obtained for 137 patients (79%). At eight weeks, patients receiving therapy had significantly higher scores than control patients on fighting spirit and significantly lower scores on helplessness, anxious preoccupation, and fatalism; anxiety; psychological symptoms; and on orientation towards health care. These differences indicated improvement in each case. At four months, patients receiving therapy had significantly lower scores than controls on anxiety; psychological symptoms; and psychological distress. Clinically, the proportion of severely anxious patients dropped from 46% at baseline to 20% at eight weeks and 20% at four months in the therapy group and from 48% to 41% and to 43% respectively among controls. The proportion of patients with depression was 40% at baseline, 13% at eight weeks, and 18% at four months in the therapy group and 30%, 29%, and 23% respectively in controls. CONCLUSIONS--Adjuvant psychological therapy produces significant improvement in various measures of psychological distress among cancer patients. The effect of therapy observed at eight weeks persists in some but not all measures at four month follow up.

(97) Fallowfield LJ, Truth may hurt but deceit hurts more: communication in palliative care, Palliat Med, 2002 Jul;16(4):297-303
Healthcare professionals often censor their information giving to patients in an attempt to protect them from potentially hurtful, sad or bad news. There is a commonly expressed belief that what people do not know does not harm them. Analysis of doctor and nurse/patient interactions reveals that this well-intentioned but misguided assumption about human behaviour is present at all stages of cancer care. Less than honest disclosure is seen from the moment that a patient reports symptoms, to the confirmation of diagnosis, during discussions about the therapeutic benefits of treatment, at relapse and terminal illness. This desire to shield patients from the reality of their situation usually creates even greater difficulties for patients, their relatives and friends and other members of the healthcare team. Although the motivation behind economy with the truth is often well meant, a conspiracy of silence usually results in a heightened state of fear, anxiety and confusion--not one of calm and equanimity. Ambiguous or deliberately misleading information may afford short-term benefits while things continue to go well, but denies individuals and their families opportunities to reorganize and adapt their lives towards the attainment of more achievable goals, realistic hopes and aspirations. In this paper, some examples and consequences of accidental, deliberate, if well-meaning, attempts to disguise the truth from patients, taken verbatim from interviews, are given, together with cases of unintentional deception or misunderstandings created by the use of ambiguous language. We also provide evidence from research studies showing that although truth hurts, deceit may well hurt more. 'I think the best physician is the one who has the providence to tell to the patients according to his knowledge the present situation, what has happened before, and what is going to happen in the future' (Hippocrates).

(98) Der beste Arzt scheint mir der zu sein, der sich auf Voraussicht versteht. Denn wenn er den gegenwärtigen und den ihm vorhergegangenen und den küfftigen Stand einer Krankheit schon vorher erkennt und den Kranken vorhersagt und ihnen erklärt, was sie unterlassen haben, dann werden sie ihm vertrauen, weil er ihren Zustand besser als sie selber erkennt, sodass die Menschen es wagen, sich dem Arzt anzuvertrauen. Ihre Therapie wird er aber am richtigsten vornehmen, wenn er aus dem gegenwärtigen Stand ihrer Krankheit deren künftigen Verlauf vorhersagt. Dal Corpus Hippocraticum di Ipocrate.

(99) Tiersma ES, Psychosocial factors and the grade of cervical intra-epithelial neoplasia: a semi-prospective study, Gynecol Oncol, 2004 Feb;92(2):603-10
OBJECTIVE: To study the influence of psychosocial factors on the grade of cervical intra-epithelial neoplasia. METHODS: The influence of psychosocial factors on the grade of cervical intra-epithelial neoplasia (CIN) was studied in a group of 342 patients with an abnormal cervical smear. Participants completed a set of questionnaires after colposcopy directed biopsy before knowing the biopsy result. Negatively rated life events, social support, and coping style were studied in relation to distress and grade of CIN. Infection with human papillomavirus (HPV) types was controlled for, as well as sick role bias caused by suspicion of having cervical cancer and distress due to the abnormal cervical smear. RESULTS: Negatively rated life events, lack of social support, and emotional coping were significant predictors for level of distress. No significant relationship was found, however, between the psychosocial factors and grade of CIN. CONCLUSION: No support was found for an influence of negatively rated life events, social support, coping style, and distress on grade of CIN.

(100) Tiersma ES, Psychosocial factors and the course of cervical intra-epithelial neoplasia: a prospective study, Gynecol Oncol, 2005 Jun;97(3):879-86
OBJECTIVE: To investigate the influence of psychosocial factors on the course of cervical intra-epithelial neoplasia (CIN). METHODS: A group of 93 patients with CIN 1 or 2 was followed for 2.25 years by half-yearly colposcopy and cytology. Negatively-rated life events, social support, and coping style were studied in relation to distress during follow-up and in relation to time till progression and regression of CIN. Human papillomavirus (HPV) infection was controlled for as well as sick role bias caused by suspicion of having cervical cancer and distress due to the abnormal cervical smear. RESULTS: During follow-up, progression was found in 20 patients (22%), stable disease in 22 patients (24%), and regression in 51 patients (55%). Negatively-rated life events and lack of social support predicted distress longitudinally. No association was found between progression or regression of CIN and negatively-rated life events, lack of social support, coping style, and distress. CONCLUSION: We found no evidence that psychosocial factors influence the course of CIN.

(101) Temoshok LR, Change is complex: rethinking research on psychosocial interventions and cancer, Integr Cancer Ther, 2002 Jun;1(2):135-45
The widely discussed 1989 study by Spiegel and colleagues, which suggested that a psychosocial group intervention affected survival in metastatic breast cancer, was not replicated by Goodwin and colleagues in 2001. We analyze methodological issues in both studies, including issues of sampling, randomization, interpretation, and the adequacy and validity of psychosocial constructs and measures to assess hypothesized ingredients of change. The notion of psychogenicity is introduced, conceived as the ability of psychosocial interventions to elicit changes hypothesized to be linked to desired medical outcomes. These considerations lead to the conclusion that there is insufficient evidence to be able to generalize from either study for or against the notion that psychosocial interventions can affect survival in breast cancer. The failure to incorporate into research designs a comprehensive understanding of how coping patterns and related factors may interact with psychosocial interventions to influence cancer progression, and to address hypothesized mediating mechanisms is discussed. Finally, strategies are proposed for future biopsychosocial and intervention research in the field of biopsychooncology.

(102) Ross L, Mind and cancer: does psychosocial intervention improve survival and psychological well-being? Eur j cancer, 2002 Jul;38(11):1447-57
The aim of this review was to evaluate the scientific evidence for an effect of psychosocial intervention on survival from cancer and well-being and in particular on anxiety and depression. A literature search yielded 43 randomised studies of psychosocial intervention. Four of the eight studies in which survival was assessed showed a significant effect, and the effect on anxiety and depression was also inconsistent, indicating three possible explanations: (i) only some of the intervention strategies affect prognosis and/or well-being and in only certain patient groups; (ii) the effect was weak, so that inconsistent results were found in the generally small study populations; or (iii) the effect was diluted by the inclusion of unselected patient groups rather than being restricted to patients in need of psychosocial support. Thus, large-scale studies with sound methods are needed in which eligible patients are screened for distress. Meanwhile, the question of whether psychosocial intervention among cancer patients has a beneficial effect remains unresolved.

(103) Edwards AG, Psychological interventions for women with metastatic breast cancer, Cochrane Database Syst Rev, 2004;(2):CD004253
BACKGROUND: There have been conflicting results from systematic reviews of psychological interventions for patients with cancer, some showing benefits for patients and others not. One early study appeared to show significant survival benefits as well as psychological benefits from a psychological intervention given to women with metastatic breast cancer. Some further studies have been undertaken, again with conflicting results. OBJECTIVES: To assess the effects of psychological interventions (educational, individual cognitive behavioural or psychotherapeutic, or group support) on psychological and survival outcomes for women with metastatic breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group Trials Register (September 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), MEDLINE (1966-October 2003), CancerLit (1983-2000), CINAHL (1982-October 2003), PsycInfo (1974-November 2003), and SIGLE (1980-November 2003). SELECTION CRITERIA: Randomised controlled trials (RCTs) of psychological interventions for women with metastatic breast cancer. Studies were included even if they were not 'intention to treat', owing to the nature of the patient group under study and the likely high loss of follow-up data. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Data about the nature and setting of the intervention, and the relevant outcome data were extracted, along with items relating to methodological quality. MAIN RESULTS: Five primary studies were identified, all group psychological interventions. Two of these were cognitive behavioural interventions and three evaluated support-expressive group therapy. The five studies of group psychological therapies for women with metastatic breast cancer showed very limited evidence of benefit arising from these interventions. Although there was evidence of short-term benefit for some psychological outcomes, in general these were not sustained at follow-up. A clearer pattern of psychological outcomes could not be discerned as a wide variety of outcome measures and durations of follow-up were used in the included studies. The possible longer survival times in women allocated to receive psychological intervention in the early study have not been replicated in the subsequent four studies (including one by members of the first study group), and overall the effects of these interventions on survival are not statistically significant (for example, odds ratio for 5 year survival 0.83 (95% confidence interval [CI] 0.53 - 1.28). REVIEWERS' CONCLUSIONS: There is insufficient evidence to advocate that group psychological therapies (either cognitive behavioural or supportive-expressive) should be made available to all women diagnosed with metastatic breast cancer. Any benefits of the interventions are only evident for some of the psychological outcomes and in the short term. The possibility of the interventions causing harm is not ruled out by the available data.

(104) Fox BH, A hypothesis about Spiegel et al.'s 1989 paper on Psychosocial intervention and breast cancer survival, Psychooncology, 1998 Sep-Oct;7(5):361-70
In a randomized prospective study of 86 metastatic breast cancer patients by Spiegel et al. in 1989, the 50 who took part in a group psychosocial intervention survived on average 18 months longer than the 36 controls who did not. Because the control survival curve looked unusually steep, lacking an expected right-skewed tail, both curves were compared with that of a population from the same region having metastatic breast cancer. When transformed to life-table format, the curves of the control sample and the regional population, neither group having had an intervention, were almost identical for a year, and differed strikingly after 20 months. This led to the hypothesis that the 12 control patients surviving for more than 20 months were an extremely aberrant sample, being subject to the strong biasing influence of possible confounders, of which a considerable number are known, but not including those accounted for in the study. Corollaries to the hypothesis are that the intervention had no effect; that the intervention curve was in fact equivalent to a control curve with mild sampling departure from that of the regional population; and that, therefore, the repetition of the study now under way would not yield confirmation of the 1989 study, but rather, would support the hypothesis and the first two corollaries.

(105) Jim HS, Strategies used in coping with a cancer diagnosis predict meaning in life for survivors, Health Psychol, 2006 Nov;25(6):753-61
The search for meaning in life is part of the human experience. A negative life event may threaten perceptions about meaning in life, such as the benevolence of the world and one's sense of harmony and peace. The authors examined the longitudinal relationship between women's coping with a diagnosis of breast cancer and their self-reported meaning in life 2 years later. Multiple regression analyses revealed that positive strategies for coping predicted significant variance in the sense of meaning in life--feelings of inner peace, satisfaction with one's current life and the future, and spirituality and faith--and the absence of such strategies predicted reports of loss of meaning and confusion (ps < .01). The importance and process of finding meaning in the context of a life stressor are discussed.

(106) Basak S, A Fourth IkappaB Protein within the NF-kappaB Signaling Module, Cell 2007 jan 26 128(2) 369,
Inflammatory NF-kappaB/RelA activation is mediated by the three canonical inhibitors, IkappaBalpha, -beta, and -varepsilon. We report here the characterization of a fourth inhibitor, nfkappab2/p100, that forms two distinct inhibitory complexes with RelA, one of which mediates developmental NF-kappaB activation. Our genetic evidence confirms that p100 is required and sufficient as a fourth IkappaB protein for noncanonical NF-kappaB signaling downstream of NIK and IKK1. We develop a mathematical model of the four-IkappaB-containing NF-kappaB signaling module to account for NF-kappaB/RelA:p50 activation in response to inflammatory and developmental stimuli and find signaling crosstalk between them that determines gene-expression programs. Further combined computational and experimental studies reveal that mutant cells with altered balances between canonical and noncanonical IkappaB proteins may exhibit inappropriate inflammatory gene expression in response to developmental signals. Our results have important implications for physiological and pathological scenarios in which inflammatory and developmental signals converge.

(107) http://www.psicologia-dinamica.it/psysito/psonco/oncologia.htm

(108) Page GG, Pre-operative versus postoperative administration of morphine: impact on the neuroendocrine, behavioural, and metastatic-enhancing effects of surgery, Br J Anaesth 1998 81(2) 216,
We have previously shown that the pre- and postoperative administration of an analgesic dose of morphine attenuated the tumour-enhancing effects of surgery. This study was undertaken to assess the relative role and exclusive importance of pre- versus postoperative morphine administration on neuroendocrine, metastatic, and behavioural outcomes of surgery in Fischer 344 rats. The natural killer (NK) sensitive mammary adenocarcinoma cell line, MADB106, was used in a lung clearance assay to assess host resistance to metastasis. Either morphine or its vehicle was administered to all rats at three times: (1) 30 min before surgery (8 mg kg-1, in saline); (2) immediately after surgery in a slow release suspension (SRS, 4 mg kg-1); and (3) 5 h after surgery at the time of tumour cell inoculation (2 mg kg-1, in SRS). Five surgery groups underwent an experimental laparotomy with halothane anaesthesia and received either the vehicle at all three times or morphine in one of four different regimens: before surgery only, at all three times, after surgery only at times 2 and 3, and after surgery total at times 2 and 3 with the preoperative dose added at time 2. Two control groups underwent anaesthesia alone and received either morphine or the vehicle at all three times. Surgery resulted in a twofold increase in tumour cell retention, which was significantly attenuated by all four morphine treatment regimens (P < 0.05). Furthermore, the two surgery groups that were treated with morphine preoperatively appeared to derive greater benefit; whereas the preoperatively treated groups exhibited a 65-70% attenuation of surgery-induced increases in tumour cell retention, only a 50% attenuation was evident in the two groups treated postoperatively. Surgery significantly reduced rearing behaviour and morphine reversed this effect such that most morphine-treated surgery groups exhibited similar levels of rearing behaviour as was observed in the unoperated animals throughout the 4-h postoperative observation period. Morphine treatment also significantly attenuated surgery-induced increases in plasma corticosterone concentrations assessed at 5 h after surgery. If such relationships hold in humans, these findings support the suggestion that the pre-surgical administration of morphine is key in optimizing its beneficial effects on surgery-induced increases in metastasis.

(109) Page GG, The role of LGL/NK cells in surgery-induced promotion of metastasis and its attenuation by morphine, Brain Behav Immun 1994 8(3) 241,
Painful stress such as surgery has been shown both to suppress immune function and to promote metastasis, although the degree to which alterations in immunity underlies the tumor-enhancing effects of surgery remains unclear. We recently reported that an experimental laparotomy results in a twofold increase in the number of lung metastases following iv injection of MADB106 tumor cells, a natural killer (NK)-sensitive mammary adenocarcinoma cell line, syngeneic to the Fischer 344 rats we studied. Further, the administration of an analgesic dose of morphine prevented these metastatic-enhancing effects of surgery. The aim of the present study was to investigate the role of NK cells in both the metastatic-enhancing effects of surgery and the attenuation of these effects by morphine. Using a simple 2 x 2 experimental design (surgery with anesthesia vs anesthesia only, and morphine vs vehicle), we found that surgery resulted in a decrease in both whole blood NK cytotoxic activity and number of circulating LGL/NK cells assessed 4 h postoperatively. In a second experiment involving an 18-h lung clearance assay, we used the mAb 3.2.3 to deplete rats of LGL/NK cells with the following rationale: if LGL/NK cells are necessary to mediate an event, then in their absence, that event should not occur. Normal and LGL/NK-depleted animals were assigned to the same four experimental groups, and radiolabeled MADB106 tumor cells were injected iv 4 h after surgery. In normal animals, there was a significant interaction between surgery and morphine such that morphine attenuated the surgery-induced increase in tumor cell retention without affecting tumor cell retention in the anesthesia groups. In the LGL/NK-depleted animals, however, although the tumor-enhancing effects of surgery remained evident, morphine did not mitigate this outcome. These results suggest that: (a) both LGL/NK cell activity and other factors independent of LGL/NK cells play a role in the surgery-induced increase in tumor cell retention; and (b) LGL/NK cells play a critical role in morphine's attenuating effects on this outcome. Finally, these results reinforce concern about the pathogenic consequences of unrelieved pain.

(110) Page GG, Morphine attenuates surgery-induced enhancement of metastatic colonization in rats, Pain 1993 54(1) 21,
Painful stressors such as surgery have been shown both to suppress immune function and to enhance tumor development. Whether the immune system mediates the tumor-enhancing effects of surgery remains unclear. Moreover, the role of postoperative pain has been largely ignored in such studies. To explore these issues, we used the MADB106 tumor, a mammary adenocarcinoma syngeneic to the subjects of this study (Fischer 344 rats) and known to be sensitive to natural killer (NK) cell activity. We found that surgery enhanced metastatic colonization and that this tumor-enhancing effect occurred only during the time in which the MADB106 tumor is sensitive to NK control. These results support the hypothesis that suppression of NK cell activity mediates the surgery-induced enhancement of metastatic colonization. Further, we found that an analgesic dose of morphine blocked the surgery-induced increase in metastasis without affecting metastasis in unoperated animals. These findings suggest that postoperative pain is a critical factor in promoting metastatic spread. If a similar relationship between pain and metastasis occurs in humans, then pain control must be considered a vital component of postoperative care.

(111) Gaspani L, The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats, J Neuroimmunol 2002 129(1-2) 18-24,
Surgery stress has been shown to be associated in rat with decreased natural killer (NK) cell activity and enhancement of tumor metastasis. We have previously shown that the analgesic drug tramadol stimulates NK activity both in the rodent and in the human. In the present study, we analyze, in the rat, tramadol ability to prevent the effect of experimental surgery on NK activity and on the enhancement of metastatic diffusion to the lung of the NK sensitive tumor model MADB106. The administration of tramadol (20 and 40 mg/kg) before and after laparatomy significantly blocked the enhancement of lung metastasis induced by surgery. In contrast, the administration of 10 mg/kg of morphine was not able to modify this enhancement. The modulation of NK activity seemed to play a central role in the effect of tramadol on MADB106 cells. In fact, both doses of tramadol were able to prevent surgery-induced NK activity suppression, while the drug significantly increased NK activity in normal non-operated animals. Morphine, that in normal rats significantly decreased NK cytotoxicity, did not prevent surgery-induced immunosuppression. The good analgesic efficacy of tramadol combined with its intrinsic immunostimulatory properties suggests that this analgesic drug can be particularly indicated in the control of peri-operative pain in cancer patients.

(112) Shavit Y, Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats. Dose and timing study, Neuroimmunomodulation 2004 11(4) 255,
OBJECTIVES: Opiates, which serve an integral role in anesthesia, suppress immune function, particularly natural killer cell cytotoxicity (NKCC). NK cells play an important role in tumor and metastasis surveillance. We reported that large-dose fentanyl anesthesia induced prolonged suppression of NKCC in patients undergoing abdominal surgery. The immune modulatory effects of opiates may depend on the interaction between dose and time of administration. The present study examined the effects of different doses of fentanyl, administered at different time points relative to tumor inoculation, on NKCC and on experimental tumor metastasis in rats. METHODS: Fischer 344 rats were injected with low or high doses of fentanyl, 6 or 2 h before, simultaneously with or 1 h after being inoculated intravenously with MADB106 tumor cells. Lung tumor retention (LTR) was assessed 4 h after, and lung tumor metastases were counted 3 weeks after tumor inoculation. NKCC was assessed 1 h after the fentanyl injection. RESULTS: At all time points, except 6 h before tumor inoculation, fentanyl (0.1-0.3 mg/kg) induced a dose-dependent increase in MADB106 LTR (2.3- to 74-fold). An intermediate dose of fentanyl (0.15 mg/kg) doubled the number of lung metastasis, and, within animal, suppressed NKCC and increased MADB106 LTR in a correlated manner. CONCLUSION: These findings indicate that fentanyl suppresses NKCC and increases the risk of tumor metastasis. Suppression of NK cells at a time when surgery may induce tumor dissemination can prove to be critical to the spread of metastases. It is suggested that the acute administration of a moderate dose of opiates during surgery should be applied cautiously, particularly in cancer patients.

(113) Page GG, Increased surgery-induced metastasis and suppressed natural killer cell activity during proestrus/estrus in rats, Breast Cancer Res Threat 1997 45(2) 159,
We have previously reported sex- and estrous-related differences in host resistance to the metastatic development of a mammary adenocarcinoma cell line, MADB106, in the Fischer 344 (F344) rat. In other studies, we found that surgery suppressed natural killer (NK) cell activity and increased the NK-sensitive metastatic development of MADB106 tumor cells. The current study was designed to explore whether sex or estrous phase at the time of surgery impacts the degree of such deleterious effects of surgery. Such estrous effects could be related to an ongoing clinical debate regarding the importance of the timing of breast cancer surgery with the menstrual cycle in premenopausal women. Mature F344 males and cycling females underwent either experimental laparotomy with halothane anesthesia, halothane anesthesia alone, or were untreated. Five hours after surgery, animals either were injected with radiolabeled MADB106 tumor cells and assessed for lung tumor cell retention 12 hours later, or underwent blood withdrawal for in vitro assessment of NK cell activity. MADB106 tumor cells metastasize only to the lungs, and lung tumor cell retention is: a) an early indicator of the number of metastases that would develop weeks later, and b) highly sensitive to in vivo levels of NK activity. This mammary adenocarcinoma cell line is syngeneic to the inbred F344 strain of rats used in our studies, thus constituting a model for breast cancer metastasis. The results indicated that sex, estrous phase, and surgery interacted in their effects on NK cell activity and tumor metastasis. MADB106 lung tumor cell retention was increased by surgery in both sexes (2- to 3-fold) compared to the anesthesia only and control groups. This increase, however, was significantly greater in proestrus/estrus (P/E) females than in metestrus/diestrus (M/D) females. Among the control animals, females in P/E exhibited significantly less NK cytotoxic activity compared to the males, and the NK activity exhibited by females in M/D was between these two groups. Surgery suppressed NK cytotoxic activity to a similar level in all groups. Possible implications of these findings for the surgical care of women with breast cancer are discussed.

(114) Besedovsky HO, Psychoneuroimmunology and cancer: fifteenth Sapporo Cancer Seminar, Cancer res, 1996 Sep 15;56(18):4278-81
http://cancerres.aacrjournals.org/cgi/reprint/56/18/4278?ijkey=f9e6ec7bd08e32d5a719b5b2b21441f363b22767&keytype2=tf_ipsecsha

(115) Sacerdote P, Opioids and the immune system, Palliat Med 2006;20 Suppl 1:s9-15
Opioid compounds such as morphine produce powerful analgesia that is effective in treating various types of pain. In addition to their therapeutic efficacy, opioids can produce several well known adverse events, and, as has recently been recognized, can interfere with the immune response. The immunomodulatory activities of morphine have been characterized in animal and human studies. Morphine can decrease the effectiveness of several functions of both natural and adaptive immunity, and significantly reduces cellular immunity. Indeed, in animal studies morphine is consistently associated with increased morbidity and mortality due to infection and worsening of cancer. However, from several animal studies it emerges that not all opioids induce the same immunosuppressive effects, and evaluating each opioid's profile is important for appropriate analgesic selection. Buprenorphine is a potent opioid that is frequently prescribed for chronic pain. Acute intracerebroventricular administration of buprenorphine has been shown in rats not to affect cellular immune responses, while a statistically significant inhibition of the immune response was observed with morphine. In mouse studies, chronic administration of buprenorphine led to immune parameters important for antimicrobial responses or for anti-tumour surveillance (lymphoproliferation, natural killer (NK)-lymphocyte activity, cytokine production, lymphocyte number) being unaffected. In contrast, levels of these immune markers were significantly reduced when the potent micro-agonist fentanyl was administered, but recovered after longer periods as tolerance developed. Because the intrinsic immunosuppressive activity varies between individual opioids, predicting the outcome on immunity can be difficult. To study this, the effects of morphine, fentanyl and buprenorphine on NK-lymphocyte activity depressed by experimental surgery were examined in rats. Treating animals immediately after surgery with equianalgesic doses of morphine and buprenorphine significantly reduced surgery-induced immunosuppression. However, buprenorphine reverted NK-lymphocyte activity to preoperative levels, while in morphine-treated rats NK-lymphocyte activity was ameliorated, although not completely. In contrast, fentanyl did not prevent immunosuppression induced by surgery. Overall, from several animal studies it emerges that buprenorphine has the more favourable profile, being a potent analgesic devoid of intrinsic immunosuppressive activity.

(116) Beilin B, Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period, Anesth Analg 1996 Mar;82(3):492-7,
Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.

(117) ----

(118) Brand SR, The effect of maternal PTSD following in utero trauma exposure on behavior and temperament in the 9-month-old infant.
In view of evidence of in utero glucocorticoid programming, and our prior observation of lower cortisol levels in 9-month-old infants of mothers with posttraumatic stress disorder (PTSD) compared to mothers without PTSD, we undertook an examination of the effect of in utero maternal stress, as determined by PTSD symptom severity, and maternal cortisol levels on behavioral outcomes in the infant. Methods: Ninety-eight pregnant women directly exposed to the World Trade Center (WTC) collapse on 9/11 provided salivary cortisol samples and completed a PTSD symptom questionnaire and a behavior rating scale to measure infant temperament, including distress to limitations, and response to novelty. Results: Mothers who developed PTSD in response to 9/11 had lower morning and evening salivary cortisol levels, compared to mothers who did not develop PTSD. Maternal morning cortisol levels were inversely related to their rating of infant distress and response to novelty (i.e., loud noises, new foods, unfamiliar people). Also, mothers who had PTSD rated their infants as having greater distress to novelty than did mothers without PTSD (t = 2.77, df = 61, P = 0.007). Conclusion: Longitudinal studies are needed to determine how the association between maternal PTSD symptoms and cortisol levels and infant temperament reflect genetic and/or epigenetic mechanisms of intergenerational transmission.

(119) Yehuda R, Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy, J Clin Endocrin Metab 2005 Jul;90(7):4115-8. Epub 2005 May 3
http://jcem.endojournals.org/cgi/reprint/90/7/4115?ijkey=3fb94906118ae5ce99eaee74d30221b9e54bd4f1
CONTEXT: Reduced cortisol levels have been linked with vulnerability to posttraumatic stress disorder (PTSD) and the risk factor of parental PTSD in adult offspring of Holocaust survivors. OBJECTIVE: The purpose of this study was to report on the relationship between maternal PTSD symptoms and salivary cortisol levels in infants of mothers directly exposed to the World Trade Center collapse on September 11, 2001 during pregnancy. DESIGN: Mothers (n = 38) collected salivary cortisol samples from themselves and their 1-yr-old babies at awakening and at bedtime. RESULTS: Lower cortisol levels were observed in both mothers (F = 5.15, df = 1, 34; P = 0.030) and babies of mothers (F = 8.0, df = 1, 29; P = 0.008) who developed PTSD in response to September 11 compared with mothers who did not develop PTSD and their babies. Lower cortisol levels were most apparent in babies born to mothers with PTSD exposed in their third trimesters. CONCLUSIONS: The data suggest that effects of maternal PTSD related to cortisol can be observed very early in the life of the offspring and underscore the relevance of in utero contributors to putative biological risk for PTSD.

(120) Bierer LM, Clinical correlates of 24-h cortisol and norepinephrine excretion among subjects seeking treatment following the world trade center attacks on 9/11, Ann NY Acad Sci 2006 Jul;1071:514-20
Whereas trauma-associated arousal has been linked fairly consistently with elevations in both glucocorticoids and catecholamines, neuroendocrine correlates of hyperarousal in the context of posttraumatic stress disorder (PTSD) have been more variable. Further, neuroendocrine predictors of the development of PTSD following trauma have been related to prior exposure, and data from several laboratories suggests that hyperarousal may develop in a neuroendocrine milieu of relatively diminished basal glucocorticoid secretion. METHODS: In this article we examined 24-h cortisol and norepinephrine excretion in 42 treatment-seeking survivors of the 9/11 World Trade Center (WTC) attacks, 32 of whom met criteria for PTSD, and 15 of whom met criteria for major depression, at the time of evaluation; 14 of the 15 subjects meeting criteria for major depression also suffered from PTSD. RESULTS: PTSD subjects' 24-h cortisol excretion (46.3 +/- 20.0 microL/dL) was lower than that of the non-PTSD cohort (72.2 +/- 22.4 microL/dL; t = 3.18, df = 37, P = 0.003), and 24-h urinary cortisol was negatively correlated with the experience of the WTC attacks as a Criterion-A event (r = -0.427, P = 0.007), and with self-rated avoidance (r = -0.466, P = 0.003) and total score (r = -0.398, P = 0.012) on the PTSD Symptom Scale (PSS). In contrast, 24-h norepinephrine excretion was not associated with the development of PTSD or with PTSD-related symptoms, but was negatively correlated with days since 9/11 at the time of evaluation (r = -0.393, P = 0.015). DISCUSSION: The latter finding suggests a relationship of norepinephrine to a dimension of stress-related arousal not captured by the symptom-rating scales chosen for this study to reflect symptoms related to PTSD and other neuropsychiatric disorders, but instead, of one to that of the sudden multidimensional life disruption suffered by the WTC survivors that applied for treatment. These data also confirm, in a naturalistic sample, the previously observed negative association of urinary cortisol excretion with development of PTSD in the aftermath of severe trauma exposure.

(121) Yehuda R, Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder, Am J Psychiatry 1995 Jul;152(7):982-6
OBJECTIVE: The authors' objective was to compare the urinary cortisol excretion of Holocaust survivors with posttraumatic stress disorder (PTSD) (N = 22) to that of Holocaust survivors without PTSD (N = 25) and comparison subjects not exposed to the Holocaust (N = 15). METHOD: Twenty-four-hour urine samples were collected, and the following day, subjects were evaluated for the presence and severity of past and current PTSD and other psychiatric conditions. RESULTS: Holocaust survivors with PTSD showed significantly lower mean 24-hour urinary cortisol excretion than the two groups of subjects without PTSD. Multiple correlation analysis revealed a significant relationship between cortisol levels and severity of PTSD that was due to a substantial association with scores on the avoidance subscale. CONCLUSIONS: The present findings replicate the authors' previous observation of low urinary cortisol excretion in combat veterans with PTSD and extend these findings to a non-treatment-seeking civilian group. The results also demonstrate that low cortisol levels are associated with PTSD symptoms of a clinically significant nature, rather than occurring as a result of exposure to trauma per se, and that low cortisol levels may persist for decades following exposure to trauma among individuals with chronic PTSD.

(122) Yehuda R, Cortisol levels in adult offspring of Holocaust survivors: relation to PTSD symptom severity in the parent and child, Psychoneuroendocrinology 2002 Jan-Feb;27(1-2):171-80,
We have previously demonstrated lower mean 24-h urinary cortisol excretion in adult offspring of Holocaust survivors with parental posttraumatic stress disorder (and lifetime PTSD), compared to offspring without parental PTSD, and to demographically similar comparison subjects. In the current study, we re-analyze data from our previously published report, plus four new subjects, to further examine the relationship between cortisol and severity of PTSD symptoms in offspring and their parents. We also examine the contribution of current depressive disorder to cortisol levels. Two-way analysis of variance revealed lifetime PTSD to be associated with significantly lower cortisol levels, while depressive disorder was associated with higher cortisol levels. The presence of parental PTSD was associated with lower cortisol excretion in the offspring only if both parents were affected. There were significant negative correlations between severity of parental PTSD and offspring urinary cortisol excretion, and between severity of offspring PTSD symptoms and urinary cortisol levels. The findings amplify our earlier descriptions of children of Holocaust survivors with PTSD as a sample 'at risk' for PTSD by demonstrating relationships between lowered cortisol excretion in these offspring and their experience of their parents' PTSD symptoms.

(123) Wolff MS, Exposures among pregnant women near the World Trade Center site on 11 September 2001, Environ Health Perspect 2005 Jun;113(6):739-48,
We have characterized environmental exposures among 187 women who were pregnant, were at or near the World Trade Center (WTC) on or soon after 11 September 2001, and are enrolled in a prospective cohort study of health effects. Exposures were assessed by estimating time spent in five zones around the WTC and by developing an exposure index (EI) based on plume reconstruction modeling. The daily reconstructed dust levels were correlated with levels of particulate matter < or = 2.5 microm in aerodynamic diameter (PM2.5; r = 0.68) or PM10 (r = 0.73-0.93) reported from 26 September through 8 October 2001 at four of six sites near the WTC whose data we examined. Biomarkers were measured in a subset. Most (71%) of these women were located within eight blocks of the WTC at 0900 hr on 11 September, and 12 women were in one of the two WTC towers. Daily EIs were determined to be highest immediately after 11 September and became much lower but remained highly variable over the next 4 weeks. The weekly summary EI was associated strongly with women's perception of air quality from week 2 to week 4 after the collapse (p < 0.0001). The highest levels of polycyclic aromatic hydrocarbon-deoxyribonucleic acid (PAH-DNA) adducts were seen among women whose blood was collected sooner after 11 September, but levels showed no significant associations with EI or other potential WTC exposure sources. Lead and cobalt in urine were weakly correlated with sigmaEI, but not among samples collected closest to 11 September. Plasma OC levels were low. The median polychlorinated biphenyl level (sum of congeners 118, 138, 153, 180) was 84 ng/g lipid and had a nonsignificant positive association with sigmaEI (p > 0.05). 1,2,3,4,6,7,8-Heptachlorodibenzodioxin levels (median, 30 pg/g lipid) were similar to levels reported in WTC-exposed firefighters but were not associated with EI. This report indicates intense bystander exposure after the WTC collapse and provides information about nonoccupational exposures among a vulnerable population of pregnant women.

(124) Rayne S, Using exterior building surface films to assess human exposure and health risks from PCDD/Fs in New York City, USA, after the World Trade Center attacks, J Hazard Mater 2005 Dec 9;127(1-3):33-9
Concentrations of tetra- through octa-chlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined in exterior window films from Manhattan and Brooklyn in New York City (NYC), USA, 6 weeks after the World Trade Center (WTC) attacks of 11 September 2001. High concentrations of the 2,3,7,8-substituted congeners (P(2378)CDD/Fs) were observed, at levels up to 6600 pg-TEQ g(-1) nearest the WTC site. An equilibrium partitioning model was developed to reconstruct total gas + particle-phase atmospheric concentrations of P(2378)CDD/Fs at each site. The reconstructed atmospheric and window film concentrations were subsequently used in a preliminary human health risk assessment to estimate the potential cancer and non-cancer risks posed to residents of lower Manhattan from these contaminants over the 6 week exposure period between the WTC attacks and sampling dates. Residents of lower Manhattan appear to have a slightly elevated cancer risk (up to 1.6% increase over background) and increased P(2378)CDD/F body burden (up to 8.0% increase over background) because of above-background exposure to high concentrations of P(2378)CDD/Fs produced from the WTC attacks during the short period between 11 September 2001, and window film sampling 6 weeks later.

(125) http://www.corriere.it/Primo_Piano/Cronache/2007/03_Marzo/11/veronesi.shtml 11.3.07, U. Veronesi: Il ricordo dello scienziato, Laura Dubini un simbolo della lotta al cancro

(126) http://www.meb.uni-bonn.de/cancernet/600317.html National Cancer Institute: Psychological Stress and Cancer

(127) http://www.aerzteblatt.de/v4/archiv/artikeldruck.asp?id=49834 Sonnenmos, Marion: Psychosoziale Aspekte onkologischer Erkrankungen: „Der Einfluss der Psyche ist sekundär“

(128) http://www.krebsinformationsdienst.de/Fragen_und_Antworten/psychische_einfluesse_krebsentstehung.html

(129) http://www.tumorzentrum-tuebingen.de/Schwarz_Vortrag_Patiententag2007.pdf Schwarz R: (2007) Psychologische Faktoren bei Krebserkrankungen

da aggiungere:

(130) Nielsen NR, Stress and breast cancer: a systematic update on the current knowledge. Nat Clin Pract Oncol 2006 Nov;3(11):612-20
A vast body of research has been carried out to examine the relationship between psychological stress and the risk of breast cancer. Previous reviews on this issue have mainly focused on stressful life events and have included both prospective and retrospective studies. The results from these reviews have revealed conflicting data. We evaluate whether stressful life events, work-related stress, or perceived global stress are differentially associated with breast cancer incidence and breast cancer relapse in prospective studies. Systematic and explicit methods were used to identify, select, and critically appraise relevant studies. The substantial variability in the manner in which stress was conceptualized and measured did not allow for the calculation of a quantitative summary estimate for the association between stress and breast cancer. Despite the heterogeneity in the results obtained, it is concluded that stress does not seem to increase the risk of breast cancer incidence. Whether stress affects the progression of breast cancer is still unclear. Studies with more thorough adjustment for confounding factors and larger studies on stress and breast cancer relapse are required to address this issue.

(131) Bergelt C, Stressful life events and cancer risk. Br J Cancer 2006 Dec 4;95(11):1579-81
In a prospective cohort study in Denmark of 8736 randomly selected people, no evidence was found among 1011 subjects who developed cancer that self-reported stressful major life events had increased their risk for cancer.

Lavori non esaminati:

Barrios A.A., & Kroger W.S.. (1975). Hypnosis as a tool in a fight against the cancer. J. Hol. Health, 1, 71-80.

Antonovsky, A.: Unraveling the mystery of health. Jossey-Bass, San Francisco 1987.

Levy S. M. (1984). Emotions and progression of cancer : a review. Advances : Journal of the Institute for the Advancement of Health, hiver, 10-15.

Cooper CL, Faragher EB. Psychosocial stress and breast cancer: the inter-relationship between stress events, coping strategies and personality. Psychol Med 1993;23:653-62

Dreyer L, Cancer risk of patients discharged with acute myocardial infarct, Epidemiology, 1998 Mar;9(2):178-83

Fawzy, F., Fawzy, N., Arndt, L., Pasnau, R. (1995) Critical review of psychosocial interventions in cancer care. Arch. Gen. Psychiatry, 52, 100-113.Fawzy, F., Fawzy, N. (1998) Group therapy in the cancer setting. J Psychosom Res 45, 3, 191-200

Fox, B. (1998) Psychosocial factors in cancer incidence and prognosis. In: In: J. Holland (ed) Psychooncology, p. 110-124. Oxford University Press New York.

Goodwin PJ, Leszcz M, Ennis M, Koopmans J, Vincent L, Guther H, Drysdale E, Hundleby M, Chochinov HM, Navarro M, Speca M, Hunter J (2001) The effect of group psychosocial support on survival in metastatic breast cancer. N Engl J Med 345(24):1719-1726

Geyer S. Life events prior to manifestation of breast cancer: a limited prospective study covering eight years before diagnosis. J Psychosom Res 1991;35:355-63

Holland, J.C. (2002). History of Psycho-Oncology: overcoming attitudinal and conceptual barriers. Psychosomatic Medicine, 64, 206-221.

Kiss, A. (1995): Psychosocial/psychotherapeutic interventions in cancer patients: consensus statment. Support Care Cancer 3, 217-218

Lewis CE, O'Sullivan C, Barraclough J, eds. The psychoimmunology of cancer. Oxford: Oxford University Press, 1994

Muslin HL, Gyargas K, Pieper WJ. Separation experience and cancer of the breast. Ann NY Acad Sci 1966;125:802-6

Newell SA, Sanson-Fisher RW, Savolainen NJ (2002) Systematic review of psychological therapies for cancer patients: overview and recommendation for future research. J Natl Cancer Inst. 17; 94 (8): 558-84

NHMRC National Health and Medical Research Council (1999). Psychosocial practice guidelines: information, support and counselling for women with breast cancer. Canberra, Australia, Http://www.health.gov.au:80/nhmrc/publications/synopses/cp61syn.htm

Petticrew M Bell R, Influence of psychological coping on survival and recurrence in people with cancer: systematic review, BMJ, 2002 Nov 9;325(7372)
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12424165

Schwarz R: Seelische Einflüsse auf Entstehung und Verlauf onkologischer Erkrankungen. Dt. Hirntumorhilfe/Brainstorm 2005; 1: 20–22.
Schwarz R: Die „Krebspersönlichkeit“ – Mythen und Forschungsresultate. Psychoneuro 2004; 4: 201–207.

Michael Spöttel: Vergebliche Hoffnung. Der Mythos von sanften und natürlichen Krebstherapien. Alibri Verlag, Aschaffenburg 2006 (libro)

JuliusHackethal: 1980 "Keine Angst vor Krebs" (libro)
...Naturgegeben seien nur »gutartige Haustierkrebse«, die durch körpereigene Abwehrkräfte in Schach gehalten würden und dementsprechend nicht behandelt werden müssten. Werde der »Haustierkrebs« allerdings seelisch und/oder körperlich misshandelt, werde ein »Raubtierkrebs« daraus. So sei Krebs in erster Linie eine »Krankheit der Seele«: Ein seelisch Gesunder sei niemals krebskrank. "Raubtierkrebs ist die biologische Gottesstrafe für jahrzehntelange Sünden gegen die Gesundheit, für Gesundheitslaster. Gott ist die Natur, Naturgesetze sind unabänderliche Gottesgesetze", schreibt Hackethal. Ergo: Krebs ist eine Strafe für ein Fehlverhalten wider die als göttlich erachtete Natur (oder vielmehr gegen das, was Hackethal für natürlich hält). Mit christlicher Heilslehre hat Hackethal zwar nichts im Sinn. Der Mensch sei von dem "Naturgott" für die Welt, nicht für Himmel oder Hölle geschaffen. Dennoch ist er von der Unsterblichkeit der Seele überzeugt: Diese lebe in den Kindern weiter. Und: Krebs könne auf Kinder und Enkel vererbt werden: »Die nach dem Tod per Seelenwanderung auf die Kinder übergegangene Seele büßt für ungesühnte Sünden weiter." Ähnliche Empfehlungen präsentiert Ha­cke­thal im Rahmen seiner »Eubios-Strategie«. Er setzt auf viel Bewegung, abwechslungsreiche Kost, wenig Alkohol, Tabak, Kaffee, Tee, viel frische Luft, ausreichend Schlaf (wichtig: zwei Stunden vor Mitternacht), Gelassenheit, usw. Und: viel Sex und viel Liebe! Da der »Fortpflanzungstrieb« der stärkste Trieb der Seele sei, bestehe eine »besonders enge Wechselbeziehung« zwischen Fortpflanzungsorganen und Krebs. Ein intensives Sexual- und Liebesleben, ist sich Hackethal sicher, macht nicht nur Spaß, sondern dient überdies der Krebsprävention. Niemals würden, glaubt Hackethal, derart vernünftig lebende Menschen an Krebs sterben. Die Eubios-Strategie wirke präventiv, die körpereigenen Abwehrkräfte würden mobilisiert. Im akuten Zustand einer Erkrankung müssten die Abwehrkräfte erst recht gestärkt werden, denn »Rückbildungen von Krebsherden beruhen (…) auf körpereigenen Abwehrkräften«. Jeder Krebsverdächtige sollte, spricht Hackethal, erst einmal weit weg in Urlaub fahren und die »starke(n) Krebsheilkräfte« eines Reizklimas auf sich wirken lassen. Anschließend stehen Entgiftungskuren auf dem Plan, insbesondere Schwitzkuren. Besonders wichtig sei aber das Sonnenbaden, möglichst nackt, denn: »Der potenteste Krebshemmer ist wahrscheinlich die Sonne«, da der Pigmentstoff Melanin direkt Krebs hemmend wirke. Warum aber, fragt sich Hackethal, bekommen auch schwarzhäutige Menschen Organkrebse? Seine Antwort lautet: Schwarze verfügten zwar über mehr Melanin, dies sei jedoch weniger mobil als das sehr mobile Melanin der gebräunten Weißen. Nur im alleräußersten Notfall dürften chirurgische Maßnahmen gewählt werden. Beide Kritiker der orthodoxen Medizin ­legen Frisch-Fromm-Fröhlich-Frei-Programme vor. Der Unterschied: Nach Windstosser soll ein asketischer Lebensstil den Menschen erlösen, Hackethal plädiert für Hedonismus.

Coyne JC: Psychotherapy and survival in cancer: The conflict between hope and evidence, Psychol Bull, 2007 May;133(3):367-94
Despite contradictory findings, the belief that psychotherapy promotes survival in people who have been diagnosed with cancer has persisted since the seminal study by D. Spiegel, J. R. Bloom, H. C. Kramer, and E. Gottheil (1989). The current authors provide a systematic critical review of the relevant literature. In doing so, they introduce some considerations in the design, interpretation of results, and reporting of clinical trials that have not been sufficiently appreciated in the behavioral sciences. They note endemic problems in this literature. No randomized clinical trial designed with survival as a primary endpoint and in which psychotherapy was not confounded with medical care has yielded a positive effect. Among the implications of the review is that an adequately powered study examining effects of psychotherapy on survival after a diagnosis of cancer would require resources that are not justified by the strength of the available evidence. ((c) 2007 APA, all rights reserved).

Cunningham AJ: A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer, Psychooncology 1998 Nov-Dec;7(6):508-17
In order to test the effect of a psychological intervention on survival from cancer, 66 women with metastatic breast cancer, all receiving standard medical care, were randomly assigned into two groups; one group (n = 30) attended the psychological intervention, consisting of 35 weekly, 2 h sessions of supportive plus cognitive behavioral therapy; the control group (n = 36) received only a home study cognitive behavioral package. No significant difference was found in survival post-randomization between the groups as assessed by a log rank test 5 years after the commencement of the study. As expected, several prognostic factors were significant predictors of survival: metastatic site, hormonal receptor status, and chemotherapy prior to randomization. While many personal and demographic variables did not influence survival, there was a significant effect of self-reported exercise (possibly due to better health). A small subgroup of intervention subjects who attended outside support groups also survived significantly longer than those who did not. The strengths and limitations of the present study are discussed, and the results contrasted with those of a well known study by Spiegel et al. (Spiegel, D., Bloom, J.R., Kraemer, H.C. and Gottheil, E. (1989) Lancet ii, 888-891). We propose that a different experimental design (correlative) may be needed to show any effect of self-help behaviors and psychological attributes in a small minority of patients.

Cunningham AJ: How psychological therapy may prolong survival in cancer patients: new evidence and a simple theory, Integr Cancer Ther 2004 Sep;3(3):214-29
This article presents new data and attempts to draw together converging lines of evidence on the mental attributes that may favor prolonged survival in the face of metastatic cancer. The authors interviewed 10 individuals with medically incurable cancers who had outlived their prognoses by from 2.2 to 12.5 years (and have all survived, a further 2 more years in most cases, between interview and publication). The authors derived, by qualitative analysis, a number of themes common to most or all of them. Three major qualities emerged: "authenticity," or a clear understanding of what was important in one's life; "autonomy," the perceived freedom to shape life around what was valued; and "acceptance," a perceived change in mental state to enhanced self-esteem, greater tolerance for and emotional closeness to others, and an affective experience described as more peaceful and joyous. Previous descriptions of "remarkable survivors" have suffered from a serious limitation: the research to date has not clarified to what extent they differed psychologically from their many peers who did not survive. The authors attempted to address this question in 2 ways. Six of the subjects were part of a protocol (the Healing Journey study) in which patients belonged to a larger group, all of whom were medically assessed prospectively, by an expert panel. A prediction of the likely duration of survival was made for each of the patients in this study, and it could be shown that those who subsequently survived were not a random sample of the whole but displayed a much higher degree of early involvement in their psychological self-help than did most of their nonsurviving peers. They also compared long survivors with 2 other groups: 6 individuals with similar diseases who had not yet received psychological help and 6 individuals from the Healing Journey study whose survival duration was at the lower end of the whole group. The patients in these comparison groups also lacked many of the most salient qualities identified among the long survivors. Many of the attributes found in the long survivors were, however, also noted in the earlier reports of remarkable survivors in the literature, which suggests that the observations may be generalizable. Putting these joint findings together with the early work of Temoshok on "type C" adaptation as a risk factor for cancer, one can see that there is a mirrored symmetry between the psychological patterns possibly promoting disease and the changed adaptations that may lead to longer survival in some cases. The authors arrive at a commonsense hypothesis: to the extent that the progression of cancer, or other chronic disease, is favored by a distorted psychological adaptation such as type C, healing may be assisted by a reversal of that adaptation--in the case of cancer, toward greater authenticity of thought and action.

Goodkin K, Psychoneuroimmunological aspects of disease progression among women with human papillomavirus-associated cervical dysplasia and human immunodeficiency virus type 1 co-infection, Int J Psychiatry Med, 1993;23(2):119-48
OBJECTIVE: Psychosocial associations have been observed with level of cervical dysplasia or "pre-cancer" and invasive cervical cancer [related to human papillomavirus (HPV) infection]. Psychoneuroimmunological relationships have been observed in human immunodeficiency virus type 1 (HIV-1) infection, which is being described in an increasing number of women. Our objective was to review these relationships regarding effects that might be expected in HIV-1 and HPV co-infected women. METHOD: This review was based on a Medline literature search supplemented by a manual search of selected journals unrepresented in that database. RESULTS: Relationships of psychosocial factors and level of cervical dysplasia were similarly observed with reference to immunological and health status in asymptomatic and early symptomatic HIV-1 infected homosexual men, suggesting that a potentiating effect may occur in HIV-1 and HPV co-infected women. Consistency of relationships across studies appeared to be enhanced by the use of a biopsychosocial model integrating the effects of life stressors, social support and coping style as well as psychiatric disorders. CONCLUSIONS: Research is indicated on the relationships between psychosocial factors, immunological status and clinical health status in this group of women. Because of the high prevalence of psychosocial risk factors for chronic psychological distress in these women and the known immunological and health status decrements occurring with progression of these two infections, a clinical screening program based on the biopsychosocial model is recommended as a means of secondary prevention. If effective in generating treatment referrals, such a program would likely improve quality of life and could aid in the determination of relationships with immunological and health status as well.

Byrnes DM, Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer, Psychom Med 1998 Nov-Dec;60(6):714-22
OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

Krongrad A, Marriage and mortality in prostate cancer, J Urol 1996 Nov;156(5):1696-70,
PURPOSE: We evaluated the association of marital status and survival in patients with prostate cancer. MATERIALS AND METHODS: Using the 146,979 prostate cancer patients of the 1973 to 1990 public use tape of the Surveillance, Epidemiology and End Results program we performed survival analysis and multivariate proportional hazards modeling to estimate the relative risk of mortality. RESULTS: Married patients had significantly longer median survival than those who were divorced, single, separated or widowed. In models that controlled for age, stage, race and treatment, married patients had a significantly lower risk of mortality than those who were divorced, single, separated or widowed. CONCLUSIONS: Several hypothetical models can explain the association of marital status and mortality in men with prostate cancer. The most attractive model relies on the putative salutary effects of being married on social support and/or mood. A social support and depressed mood model of mortality raises the possibility that in prostate cancer quality of life determines quantity of life. Understanding the relationships among marital status, social support, mood and mortality could open the way to rational strategies for postponing death in men with prostate cancer.

Gore JL: Marriage and mortality in bladder carcinoma, Cancer 2005 Sep 15;104(6):1188-94,
BACKGROUND: Being married confers significant benefits in survival for patients with a variety of chronic conditions including breast and prostate carcinoma. The authors attempted to determine whether marital status is associated with survival in patients undergoing radical cystectomy for bladder carcinoma. METHODS: The authors identified 7262 subjects from the Surveillance, Epidemiology, and End Results public-use database who underwent radical cystectomy for transitional cell carcinoma of the bladder. They performed survival analyses using Kaplan-Meier estimates and Cox proportional hazards models. The authors created multivariate models to evaluate the independent association between marital status and survival, controlling for pathologic stage, lymph node status, age, race/ethnicity, and gender. RESULTS: Married subjects were older and more often male, white, and had earlier disease stage at diagnosis. Married subjects had significantly better survival than did single or widowed subjects (P < 0.001), and married subjects revealed a trend toward better survival than separated/divorced subjects (P = 0.20). Multivariate modeling revealed that compared with single subjects, those who were married had better survival, independent of age at the time of diagnosis, gender, race/ethnicity, disease stage, and lymph node status (P < 0.001). CONCLUSIONS: Marriage was associated with improved survival in patients with bladder carcinoma, independent of other factors known to influence mortality in this population. Although the mechanisms underlying this survival advantage are unknown, possibilities include differences in cancer screening, risk behaviors, and access to medical care. The interaction between psychosocial factors and the body's immune function may further explain the differential survival in this cohort. Copyright 2005 American Cancer Society.

Burke MA: Stress and the development of breast cancer: a persistent and popular link despite contrary evidence, Cancer 1997 Mar 1;79(5):1055-9,

Bleiker EM, Psychosocial factors in the etiology of breast cancer: review of a popular link, Patient Educ Couns 1999 Jul;37(3):201-14,
Breast cancer is the most frequently occurring type of cancer in women in the western world. The etiology of a large proportion of breast cancers is still unexplained, and the possibility that psychosocial factors could play a role is not ruled out. Already in pre-Christian times, it was assumed that psychological factors might play a significant role in the development of breast cancer. However, studies have failed to produce conclusive results. There is still a lack of knowledge on the relationship between breast cancer development and psychosocial factors such as stressful life events, coping styles, depression, and the ability to express emotions. The results of this review show that there is not enough evidence that psychosocial factors like 'ways of coping' or 'non-expression of negative emotions', play a significant role in the etiology of breast cancer.

Byrnes DM, Stressful events, pessimism, natural killer cell cytotoxicity, and cytotoxic/suppressor T cells in HIV+ black women at risk for cervical cancer, Psychosom Med 1998 Nov-Dec;60(6):714-22,
OBJECTIVE: This study examines whether stressful negative life events and pessimism were associated with lower natural killer cell cytotoxicity (NKCC) and T cytotoxic/suppressor cell (CD8+CD3+) percentage in black women co-infected with human immunodeficiency virus Type 1 (HIV-1) and human papillomavirus (HPV), a viral initiator of cervical cancer. METHOD: Psychosocial interviews, immunological evaluations, and cervical swabs for HPV detection and subtyping were conducted on 36 HIV+ African-American, Haitian, and Caribbean women. RESULTS: Greater pessimism was related to lower NKCC and cytotoxic/suppressor cells after controlling for presence/absence of HPV Types 16 or 18, behavioral/lifestyle factors, and subjective impact of negative life events. CONCLUSIONS: A pessimistic attitude may be associated with immune decrements, and possibly poorer control over HPV infection and increased risk for future promotion of cervical dysplasia to invasive cervical cancer in HIV+ minority women co-infected with HPV.

Garssen B: On the role of immunological factors as mediators between psychosocial factors and cancer progression, Psychiatry Res 1999 Jan 18;85(1):51-61,
Thirty-eight prospective studies on the role of psychological factors in cancer initiation and progression are reviewed. Despite the availability of many prospective studies, there is no certainty about the role of any specific factor. An important reason might be that the interactions among several psychological factors, and the interactions of psychological and biomedical risk factors, have rarely been studied. Some evidence has been found that a low level of social support, a tendency towards helplessness, and repression of negative emotions are factors that promote cancer progression. The effect of psychological factors has been more convincingly demonstrated with respect to cancer progression than cancer initiation, and more convincingly in intervention than in natural history studies. Possible mechanisms mediating associations between psychological factors and disease outcome are discussed. The role of immunosurveillance seems modest overall, and alternative pathways are suggested.

Garssen B: Psychological factors and cancer development: evidence after 30 years of research, Clin Rsychol Rev 2004 Jul;24(3):315-38,
The question whether psychological factors affect cancer development has intrigued both researchers and patients. This review critically summarizes the findings of studies that have tried to answer this question in the past 30 years. Earlier reviews, including meta-analyses, covered only a limited number of studies, and included studies with a questionable design (group-comparison, cross-sectional or semiprospective design). This review comprises only longitudinal, truly prospective studies (N=70). It was concluded that there is not any psychological factor for which an influence on cancer development has been convincingly demonstrated in a series of studies. Only in terms of 'an influence that cannot be totally dismissed,' some factors emerged as 'most promising': helplessness and repression seemed to contribute to an unfavorable prognosis, while denial/minimizing seemed to be associated with a favorable prognosis. Some, but even less convincing evidence, was found that having experienced loss events, a low level of social support, and chronic depression predict an unfavorable prognosis. The influences of life events (other than loss events), negative emotional states, fighting spirit, stoic acceptance/fatalism, active coping, personality factors, and locus of control are minor or absent. A methodological shortcoming is not to have investigated the interactive effect of psychological factors, demographic, and biomedical risk factors.

Temoshok L, Personality, coping style, emotion and cancer: towards an integrative model, Cancer Surv 1987;6(3):545-67,
What this paper attempts, which may be different than previous reviews of the literature regarding the role of certain psychosocial factors and cancer initiation/progression, is to propose a model wherein seemingly discrepant findings may be integrated and understood. For this task, a representative but not an exhaustive review of studies was conducted, which revealed surprising consistencies, given the heterogeneity of designs, measures and cancer sites. Evidence converges on a constellation of factors that appears to predispose some individuals to develop cancer more readily or to progress more quickly through its stages. These factors include (a) certain personality traits or coping styles, which were discussed under the rubric of 'Type C'; (b) difficulty in expressing emotions; and (c) an attitude or tendency toward helplessness/hopelessness. Next, illustrative discrepancies across studies were presented. In order to make sense of these seemingly discrepant results, a process model of coping style and psychological-physiological homoeostasis was proposed. This model may be used to understand why some studies have found that Type C is associated with cancer outcome measures, while others have found that helplessness/hopelessness or emotional expression is related to outcome. We would expect that these differences are attributable to the point in the cancer and coping process at which psychological assessment was conducted.

Gross J: Emotional expression in cancer onset and progression, Soc Sci Med 1989;28(12):1239-48,
Despite the intensive biomedical research in oncology since World War II, recent studies show a steady increase in age-adjusted mortality for all kinds of cancer. This findings gives impetus to the efforts of researchers who have adopted the biopsychosocial model. Systematic research using such a model has shown several psychosocial factors to be associated with cancer onset and progression, and Temoshok has recently suggested a theoretical model which unifies these findings. In this paper, I consider the evidence that one of these psychosocial factors, emotional expression, may be directly involved in cancer onset and progression. I review 18 relevant studies, discuss how one might operationalize the term 'emotional expression', and make 12 suggestions for future research.

Temoshok LR: Change is complex: rethinking research on psychosocial interventions and cancer, Integr Cancer Ther 2002 Jun;1(2):135-45, The widely discussed 1989 study by Spiegel and colleagues, which suggested that a psychosocial group intervention affected survival in metastatic breast cancer, was not replicated by Goodwin and colleagues in 2001. We analyze methodological issues in both studies, including issues of sampling, randomization, interpretation, and the adequacy and validity of psychosocial constructs and measures to assess hypothesized ingredients of change. The notion of psychogenicity is introduced, conceived as the ability of psychosocial interventions to elicit changes hypothesized to be linked to desired medical outcomes. These considerations lead to the conclusion that there is insufficient evidence to be able to generalize from either study for or against the notion that psychosocial interventions can affect survival in breast cancer. The failure to incorporate into research designs a comprehensive understanding of how coping patterns and related factors may interact with psychosocial interventions to influence cancer progression, and to address hypothesized mediating mechanisms is discussed. Finally, strategies are proposed for future biopsychosocial and intervention research in the field of biopsychooncology.

Temoshok LR, Rethinking research on psychosocial interventions in biopsychosocial oncology: an essay written in honor of the scholarly contributions of Bernard H. Fox, Psychooncology 2004 Jul;13(7):460-7.
In his best known contribution to the field of psychooncology, the late Dr Bernard H. Fox applied his breadth of scholarship in biopsychosocial cancer epidemiology to address the question of whether and to what extent stress and other psychosocial factors may contribute to cancer risk. Less well known but equally important to the field is his incisive critique of the 1989 study by Spiegel et al. on survival time of patients with metastatic breast cancer following a psychosocial intervention. This essay represents an attempt to take Fox's line of thought to the next logical level of rethinking research on psychosocial interventions in biopsychosocial oncology. Following an analysis of the inadequacy of randomized clinical trials (RCT) to evaluate the causal effects of psychosocial interventions on cancer outcomes and distinguish these from mere prediction, an integrated RCT design is suggested to take into account the psychogenicity of a given intervention, potential mediating mechanisms, and individual differences that could help illuminate hypothesized causal processes linking an experimental intervention and cancer outcomes. Copyright 2004 John Wiley & Sons, Ltd.

http://cancerres.aacrjournals.org/cgi/reprint/56/18/4278?ijkey=d6793ae76f6955711e8725e39f20b95e4d0efe2b&keytype2=tf_ipsecsha

http://www.ipos-society.org/professionals/meetings-ed/core-curriculum/communication/it/player.html

Ptacek JT, Health care providers' perspectives on breaking bad news to patients. Crit Care Nurs Q, 2000 Aug;23(2):51-9
This article reports the results of an investigation designed to obtain descriptive information about what typically transpires in bad news transactions between patients and physicians. A sample of 115 health care providers who were attending a 1-day workshop on palliative care issues responded to questions regarding bad news transactions between physicians and patients. Results indicated that giving the news in person, giving the news in a private place, having patient support providers present, and using a warm and caring tone are highly typical of bad news transactions, whereas exploring patient emotional reactions, relying on touch, delivering the news at the patient's pace, and providing written information are less typical. Nurses and physicians diverged in the perceptions about what typically transpires, suggesting that studies focusing only on physician reports or recommendations may be misleading. These data also point to the need to obtain other views of bad news transactions, and they argue for research designed to assess the relation between actual patient-physician encounters and subsequent patient-related outcomes.

Kaplan SH, Impact of the doctor-patient relationship: breaking bad news review of literature, JAMA 1996 276 496,
OBJECTIVE: To review the literature on breaking bad news while highlighting its limitations and describing a theoretical model from which the bad news process can be understood and studied. DATA SOURCES: Sources were obtained through the MEDLINE database, using "bad news" as the primary descriptor and limiting the sources to English-language articles published since 1985. STUDY SELECTION AND EXTRACTION: All articles dealing specifically with bad news were examined. These works included letters, opinions, reviews, and empirical studies. Recommendations from these articles were examined, sorted into discrete categories, and summarized. DATA SYNTHESIS: The 13 most consistently mentioned recommendations (eg, delivering the news at the patient's pace, conveying some hope, and giving the news with empathy) were examined. CONCLUSION: Although much has been written on the topic of breaking bad news, the literature is in need of empirical work. Research should begin with the simple question of whether how the news is conveyed accounts for variance in adjustment before moving to more specific questions about which aspects of conveying bad news are most beneficial. It is suggested that the bad news process can be understood from the transactional approach to stress and coping.

Farber NJ, The good news about giving bad news to patients, J Gen Intern Med 2002 Dec;17(12):914-22,
BACKGROUND: There are few data available on how physicians inform patients about bad news. We surveyed internists about how they convey this information. METHODS: We surveyed internists about their activities in giving bad news to patients. One set of questions was about activities for the emotional support of the patient (11 items), and the other was about activities for creating a supportive environment for delivering bad news (9 items). The impact of demographic factors on the performance of emotionally supportive items, environmentally supportive items, and on the number of minutes reportedly spent delivering news was analyzed by analysis of variance and multiple regression analysis. RESULTS: More than half of the internists reported that they always or frequently performed 10 of the 11 emotionally supportive items and 6 of the 9 environmentally supportive items while giving bad news to patients. The average time reportedly spent in giving bad news was 27 minutes. Although training in giving bad news had a significant impact on the number of emotionally supportive items reported (P <.05), only 25% of respondents had any previous training in this area. Being older, a woman, unmarried, and having a history of major illness were also associated with reporting a greater number of emotionally supportive activities. CONCLUSIONS: Internists report that they inform patients of bad news appropriately. Some deficiencies exist, specifically in discussing prognosis and referral of patients to support groups. Physician educational efforts should include discussion of prognosis with patients as well as the availability of support groups.
link: http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12472927

Silliman RA, The impact of age, marital status, and physician-patient interactions on the care of older women with breast carcinoma, Cancer 1997 Oct 1;80(7):1326-34,
Understanding why older women with breast carcinoma do not receive definitive treatment is critical if disparities in mortality between younger and older women are to be reduced. With this in mind, the authors studied 302 women age > or =55 years with early stage breast carcinoma. Data were collected from surgical records and in telephone interviews with the women. The main outcome was receipt of definitive primary tumor therapy, defined either as modified radical mastectomy or as breast-conserving surgery with axillary dissection followed by radiation therapy. The majority (56%) of the women underwent breast-conserving surgery and axillary dissection followed by radiation therapy. After statistical control for four variables (comorbidity, physical function, tumor size, and lymph node status), patients' ages, marital status, and the number of times breast carcinoma specialists discussed treatment options were significantly associated with the receipt of definitive primary tumor therapy. The authors concluded that when older women have been newly diagnosed with breast carcinoma and there is clinical uncertainty as to the most appropriate therapies, patients may be better served if they are offered choices from among definitive therapies. In discussing therapies with them, physicians must be sensitive to their fears and concerns about the monetary costs and functional consequences of treatment in relation to the expected benefits.

Bahnson CB: Stress and cancer: The state of the art, Psychosomatics 21: 975-981, 1980,
Although it has been repeatedly recognized from antiquity that melancholy and grief may precede the development of cancer, a body of evidence has now accumulated of a common personal background and personality makeup in many cancer patients. A recurrent theme is a feeling of loneliness and hopelessness stemming from the lack of a protected and loving childhood. Such persons harbor chronic underlying feelings of depletion, emptiness, and resentment because they are unloved. Development of a personality marked by self-containment, inhibition, rigidity, repression, and regression precedes cancer, which may involve somatic (cellular) "regression." The author surveys the literature and provides an illustrative case report to support his hypothesis.

Christine Reynaert, « Psychogenèse » du cancer : entre mythes, abus et réalité, Bulletin du Cancer Vol 87 numero 9 655 sept 2000. testo integrale: http://www.john-libbey-eurotext.fr/fr/revues/medecine/bdc/e-docs/00/01/13/99/article.md?type=text.html

Vedi anche: Quirino Zangrilla: Cancro e psiche: tra intervento scientifico e posizione di onnipotenza

prima version: 8.2.2007
ultima modificazione: 1.5.2007

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