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Psychosomatic Aspects of Pancreatic Cancer
Editorial Pancreatology 2003;3:273–275 DOI: 10.1159/000071764
Psychosomatic Aspects of Pancreatic Cancer Nikos Zilikis a Christos Dervenis b a Psychiatric b 1st
Department, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Department of Surgery, Agia Olga Hospital, Athens, Greece
For many years, pancreatic cancer (PC) was thought to present mainly with painless jaundice. However, a closer look at patients’ histories revealed different patterns of presentation. Psychosomatic symptoms need more attention from clinicians, who should have in mind that a malignancy, probably pancreatic, could be behind them. As Holland and Rowland [1] noted in their reference textbook of psychooncology, ‘there has been a long-held belief among clinicians that pancreatic cancer patients at times have a history of unexplained depression and distress that preceded the appearance of typical pancreatic cancer symptoms ...’ There are indeed very early clinical case reports, beginning in the 1920s, describing a triad of depression, anxiety and premonition of impending doom in PC patients. Taken in chronological order, some of the older reports reflect the concepts and theories dominant at each time: ‘Nervous symptoms at earliest manifestations ...’ [2]; ‘Psychic and neurological manifestations ...’ [3]; ‘Two cases simulating psychogenic illness ...’ [4]; ‘Psychiatric manifestations of PC’ [5, 6]. We should also mention two older retrospective studies, based on patients’ chart reviews, in which the authors reported a prevalence of psychiatric symptoms in PC patients of 10–20% [7]. So, very early on, clinicians were confronted with the question of whether this phenomenon was medical folklore or a psychiatric syndrome associated specifically with PC. This stimulating and, one could say, intriguing ques-
tion led to further studies, and with time, to more systematic research, which contributed to a more complete view of the problem, as the aforementioned early reports were based on isolated clinical observations and problematic methodologies such as chart review. A study at the Mayo Clinic done by Fras et al. [8] was the first to provide a prospective observation. Patients with symptoms suspicious of an abdominal neoplasm were assessed at admission with the Minnesota Multiphasic Personality Inventory. Depression, anxiety and loss of ambition were present in 76% of patients who received a diagnosis of PC at the time of surgery, as compared to 20% of patients who were found to have other abdominal neoplasms. A similar prospective unpublished study [9] reported significantly higher depression scores at the time of admission among patients subsequently found to have PC, as compared to patients who received a diagnosis of abdominal tumor not of pancreatic origin. Another very interesting study is that conducted by Holland et al. [10] on a sample of 218 patients with diagnosed gastric cancer and PC who were about to undergo chemotherapy. Using the Profile of Mood States, the authors confirmed once more the ‘significantly greater disturbance in the PC patients on the individual dimensions of depression, fatigue, tension-anxiety, and confusion-bewilderment and on the global dimension of total mood disturbance’ [10]. The particular interest of this study is that it did not only focus on anxiety-depression,
ABC
© 2003 S. Karger AG, Basel and IAP 1424–3903/03/0034–0273$19.50/0
Fax + 41 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/pan
Christos Dervenis, MD Head, 1st Department of Surgery 3–5, Agias Olgas Str. GR–14233 Athens (Greece) Tel. +30 1 277 54 67, Fax +30 1 279 39 69, E-Mail [email protected]
but also assessed dimensions of distress other than this couplet of typical psychiatric symptoms. Finally, in a very recent study by Zabora et al. [11] conducted on a very large sample (n = 4,496) to determine the prevalence of psychological distress according to cancer site, the rates varied from 43.4 to 29.6%, with PC patients producing the highest scores for anxiety and depression symptoms. So, we may say that today there is clinical evidence that in PC patients, psychological disturbances, in particular depression and anxiety, occur more frequently than in other cancer patients, practically in about half of them [12]. What remains a particular and, one could say, intriguing feature is that in these patients, psychiatric symptoms are not only present in individuals with a known cancer, but they often precede the appearance of physical symptoms of PC. The interest in explaining and understanding this phenomenon is not only scientific or theoretical, it is also of clinical importance for the treatment and care of these patients.
Trends in Research
The limits of this article only allow a brief review of the main currents of thought in psychosomatic medicine or psychosomatics. The distinct use of these two terms is related to their corresponding to the two poles of the otherwise unified field of clinical and research activity regarding the interrelations between biological and mental/psychological processes in the individual; namely, the biological and psychodynamic-psychoanalytical approach. A challenge for biological psychiatry, this problem has received some explanations, to the extent current knowledge allows for. They focus mainly on depression associated with PC and are based on the neurotransmitter hypothesis for depression. The first, one might say classical explanation is that a tumor-mediated paraneoplastic syndrome exists, and that the production of a false neurotransmitter is responsible for the patients’ mood alteration. In another vein, that of the psychoimmunological hypotheses, Brown and Paraskevas [13] postulate that tumor basic protein released from cancer cells may induce an immune response consisting of either antibodies or cytotoxic T cells or both. Through complex mechanisms, the basis of depressive illness could be (1) reduction in the activity of serotonin due to the interaction of antibodies with 5-HT receptors, or (2) nonmetastatic tissue damage
274
Pancreatology 2003;3:273–275
in the brain by T lymphocytes (carcinomatous encephalomyeloneuropathy). In support of these biological hypotheses, some cases are reported where anxiety and depression, resistant to psychiatric treatment, improved or resolved following excision of the tumor [12, 14, 15]. From another perspective, the psychodynamic-psychoanalytical point of view (it should be remembered here that most of the pioneers in psychosomatics come from this discipline), the presence of diffuse, generalized anxiety as well as of a particular type of depression, ‘essential depression’ [16, 17], has been considered characteristic of the mental functioning of individuals vulnerable or susceptible to developing severe somatic illness. Here again, these symptoms both precede the – as it is called in terms of psychosomatics – somatization, and may also be present during the manifest illness. In his pioneering work, Pierre Marty and his followers at the Institut de Psychosomatique de Paris also stressed the presence of another characteristic, namely the traumatic mode of mental functioning observed in these patients, which can be linked to the premonition of impending doom reported in the very early observations [18]. An approach ‘bridging’ the two already mentioned comes again from the modern and promising field of psychoneuroimmunology. In a review of relevant studies including both clinical and experimental data, KiecoltGlaser and Glaser [19] made the following conclusion: ‘considerable evidence has accumulated demonstrating psychosocial or behavioral modification of immune function’. In particular, chronic stress seems to produce longer-term autonomic, endocrinologic and immunologic alterations. The authors consider this relation in two ways: (1) from the etiological perspective (the individual’s susceptibility to developing a somatic illness), and (2) in terms of the effects of therapeutic interventions in cancer patients (improvement of immune function, course of the disease). Finally, another important parameter to be taken into account is the relative downregulation of the immune function in PC patients due to aging (as they are usually middle-aged or older).
Psychiatric Symptoms as Reactive Disorders
In clinical practice, the most common situation we are confronted with is that of a patient with a known cancer at all stages of the course of the disease: from the diagnostic procedure, through the different phases of treatment and
Zilikis/Dervenis
to terminal care. And in the case of PC patients, we are all aware of the very poor prognosis. What we see, then, are the patient’s reactions and ways of coping and adapting – in other terms, of psychic reorganization – to having such a cancer. The way an individual will react to this new life situation depends mainly on his/her personality structure, in other words, the mechanisms of defense that he/she has at his/her disposal. The psychiatric symptoms that will eventually be produced are then ‘reactive disorders’, the most common being anxiety and depressive symptoms. Apart from individual characteristics, any clinician should always consider the role of the supportive systems existing in the patient’s environment. Thus, we move to the psychosocial perspective, including the family, the patient’s other social references and the new agent brought into his/her life by the illness, that is the medical world. In the management of PC patients, all these factors and parameters must be taken into account in a ‘holistic’ approach, with each health professional in charge of the patient’s care finding his/her own specific role while at the same time functioning complementarily with the others. The aim of such a joint effort is to ensure comprehensive care of our patients – the family included – and a quality of life for which the mere palliative or paregoric attitude is not enough.
Conclusions
Although the presence of psychiatric symptoms and psychological distress in general was recognized very early in PC patients, the existing literature shows that a coordinated, systematic study of the problem has not been undertaken yet. Despite the considerable advances in our understanding of the biopsychological mechanisms and processes of this phenomenon, questions still remain unanswered, calling for further research. However, from existing clinical evidence, we may suggest that psychiatric aspects in PC patients could be understood in two ways: (1) considering the role of neurobiological and immunological alterations related to the illness process itself, and (2) taking into account the patient’s personality organization for the production of reactive disorders as part of the overall adaptation to the illness. PC appears to be not only a good example, but, moreover, a paradigm, in that it constitutes a field open to joint research by gastroenterologists, psychiatrists and neuroimmunologists. Such a combined effort will allow for a better understanding of illness as a whole, and for a continuous ‘mutual training’ between clinicians from different specialties, from which both we and our patients can only benefit.
References 1 Holland JC, Rowland JH: Handbook of Psycho-Oncology: Psychological Care for the Patient with Cancer. New York, Oxford University Press, 1990. 2 Yaskin JD: Nervous symptoms at earliest manifestations of carcinoma of the pancreas. JAMA 1931;96:1664–1668. 3 Latter KA, Wilbur DL: Psychic and neurological manifestations of carcinoma of the pancreas. Mayo Clinic Proc 1937;12:457–462. 4 Savage C, Butcher W, Noble D: Psychiatric manifestations in pancreatic disease. J Clin Psychopathol 1952;13:9–16. 5 Perlas AP, Faillace LA: Case reports: Psychiatric manifestations of carcinoma of the pancreas. Am J Psychiatry 1964;121:182. 6 Karlinger W: Psychiatric manifestations of cancer of the pancreas. N Engl J Med 1967;56: 2251–2252. 7 Birnbaum D, Kleesberg J: Carcinoma of the pancreas: A clinical study based on 84 cases. Ann Intern Med 1958;48:1171–1184.
Editorial
8 Fras I, Litin EM, Pearson JS: Comparison of psychiatric symptoms in carcinoma of the pancreas with those in some other intra-abdominal neoplasms. Am J Psychiatry 1967;123:1553– 1562. 9 Klatchko B, Gorzynski JG: A prospective controlled study of depression in patients with pancreatic and other intra-abdominal malignancies; presented at the annual meeting of the American Psychosomatic Society, Denver, March 1982. 10 Holland JCB, Korzun AH, Tross S, Silberfarb P, Perry M, Comis R, Oster M: Comparative psychological disturbance in patients with pancreatic and gastric cancer. Am J Psychiatry 1986;143:982–986. 11 Zabora J, Brintzenhofe Szoc K, Curbow B, Hooker C, Piantadosi S: The prevalence of psychological distress by cancer site. Psychooncology 2001;10:19–28. 12 Passik SD, Roth AJ: Anxiety symptoms and panic attacks preceding pancreatic cancer diagnosis. Psychooncology 1999;8:268–272.
13 Brown JH, Paraskevas F: Cancer and depression: Cancer presenting with depressive illness: An autoimmune disease? Br J Psychiatry 1982; 141:227–232. 14 Pomara NP, Gershon S: Treatment-resistant depression in an elderly patient with pancreatic carcinoma: Case report. J Clin Psychiatry 1984;45:439–440. 15 Olsen DB, Abraham JH: Neuropsychiatric disorders in insulinoma (in Danish). Ugeskr Laeger 1999;161:1420–1421. 16 Marty P: Les mouvements individuels de vie et de mort. Paris, Payot, 1976. 17 Marty P: L’ordre psychosomatique. Paris, Payot, 1980. 18 Marty P: The process of somatization; in Krakowski AJ, Kimball CP (eds): Psychosomatic Medicine. New York, Plenum, 1983, pp 429– 437. 19 Kiecolt-Glaser JK, Glaser R: Psychoneuroimmunology and health consequences: Data and shared mechanisms. Psychosom Med 1995;57: 269–274.
Pancreatology 2003;3:273–275
275
Psychosomatic Aspects of Pancreatic Cancer Nikos Zilikis a Christos Dervenis b a Psychiatric b 1st
Department, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Department of Surgery, Agia Olga Hospital, Athens, Greece
For many years, pancreatic cancer (PC) was thought to present mainly with painless jaundice. However, a closer look at patients’ histories revealed different patterns of presentation. Psychosomatic symptoms need more attention from clinicians, who should have in mind that a malignancy, probably pancreatic, could be behind them. As Holland and Rowland [1] noted in their reference textbook of psychooncology, ‘there has been a long-held belief among clinicians that pancreatic cancer patients at times have a history of unexplained depression and distress that preceded the appearance of typical pancreatic cancer symptoms ...’ There are indeed very early clinical case reports, beginning in the 1920s, describing a triad of depression, anxiety and premonition of impending doom in PC patients. Taken in chronological order, some of the older reports reflect the concepts and theories dominant at each time: ‘Nervous symptoms at earliest manifestations ...’ [2]; ‘Psychic and neurological manifestations ...’ [3]; ‘Two cases simulating psychogenic illness ...’ [4]; ‘Psychiatric manifestations of PC’ [5, 6]. We should also mention two older retrospective studies, based on patients’ chart reviews, in which the authors reported a prevalence of psychiatric symptoms in PC patients of 10–20% [7]. So, very early on, clinicians were confronted with the question of whether this phenomenon was medical folklore or a psychiatric syndrome associated specifically with PC. This stimulating and, one could say, intriguing ques-
tion led to further studies, and with time, to more systematic research, which contributed to a more complete view of the problem, as the aforementioned early reports were based on isolated clinical observations and problematic methodologies such as chart review. A study at the Mayo Clinic done by Fras et al. [8] was the first to provide a prospective observation. Patients with symptoms suspicious of an abdominal neoplasm were assessed at admission with the Minnesota Multiphasic Personality Inventory. Depression, anxiety and loss of ambition were present in 76% of patients who received a diagnosis of PC at the time of surgery, as compared to 20% of patients who were found to have other abdominal neoplasms. A similar prospective unpublished study [9] reported significantly higher depression scores at the time of admission among patients subsequently found to have PC, as compared to patients who received a diagnosis of abdominal tumor not of pancreatic origin. Another very interesting study is that conducted by Holland et al. [10] on a sample of 218 patients with diagnosed gastric cancer and PC who were about to undergo chemotherapy. Using the Profile of Mood States, the authors confirmed once more the ‘significantly greater disturbance in the PC patients on the individual dimensions of depression, fatigue, tension-anxiety, and confusion-bewilderment and on the global dimension of total mood disturbance’ [10]. The particular interest of this study is that it did not only focus on anxiety-depression,
ABC
© 2003 S. Karger AG, Basel and IAP 1424–3903/03/0034–0273$19.50/0
Fax + 41 61 306 12 34 E-Mail [email protected] www.karger.com
Accessible online at: www.karger.com/pan
Christos Dervenis, MD Head, 1st Department of Surgery 3–5, Agias Olgas Str. GR–14233 Athens (Greece) Tel. +30 1 277 54 67, Fax +30 1 279 39 69, E-Mail [email protected]
but also assessed dimensions of distress other than this couplet of typical psychiatric symptoms. Finally, in a very recent study by Zabora et al. [11] conducted on a very large sample (n = 4,496) to determine the prevalence of psychological distress according to cancer site, the rates varied from 43.4 to 29.6%, with PC patients producing the highest scores for anxiety and depression symptoms. So, we may say that today there is clinical evidence that in PC patients, psychological disturbances, in particular depression and anxiety, occur more frequently than in other cancer patients, practically in about half of them [12]. What remains a particular and, one could say, intriguing feature is that in these patients, psychiatric symptoms are not only present in individuals with a known cancer, but they often precede the appearance of physical symptoms of PC. The interest in explaining and understanding this phenomenon is not only scientific or theoretical, it is also of clinical importance for the treatment and care of these patients.
Trends in Research
The limits of this article only allow a brief review of the main currents of thought in psychosomatic medicine or psychosomatics. The distinct use of these two terms is related to their corresponding to the two poles of the otherwise unified field of clinical and research activity regarding the interrelations between biological and mental/psychological processes in the individual; namely, the biological and psychodynamic-psychoanalytical approach. A challenge for biological psychiatry, this problem has received some explanations, to the extent current knowledge allows for. They focus mainly on depression associated with PC and are based on the neurotransmitter hypothesis for depression. The first, one might say classical explanation is that a tumor-mediated paraneoplastic syndrome exists, and that the production of a false neurotransmitter is responsible for the patients’ mood alteration. In another vein, that of the psychoimmunological hypotheses, Brown and Paraskevas [13] postulate that tumor basic protein released from cancer cells may induce an immune response consisting of either antibodies or cytotoxic T cells or both. Through complex mechanisms, the basis of depressive illness could be (1) reduction in the activity of serotonin due to the interaction of antibodies with 5-HT receptors, or (2) nonmetastatic tissue damage
274
Pancreatology 2003;3:273–275
in the brain by T lymphocytes (carcinomatous encephalomyeloneuropathy). In support of these biological hypotheses, some cases are reported where anxiety and depression, resistant to psychiatric treatment, improved or resolved following excision of the tumor [12, 14, 15]. From another perspective, the psychodynamic-psychoanalytical point of view (it should be remembered here that most of the pioneers in psychosomatics come from this discipline), the presence of diffuse, generalized anxiety as well as of a particular type of depression, ‘essential depression’ [16, 17], has been considered characteristic of the mental functioning of individuals vulnerable or susceptible to developing severe somatic illness. Here again, these symptoms both precede the – as it is called in terms of psychosomatics – somatization, and may also be present during the manifest illness. In his pioneering work, Pierre Marty and his followers at the Institut de Psychosomatique de Paris also stressed the presence of another characteristic, namely the traumatic mode of mental functioning observed in these patients, which can be linked to the premonition of impending doom reported in the very early observations [18]. An approach ‘bridging’ the two already mentioned comes again from the modern and promising field of psychoneuroimmunology. In a review of relevant studies including both clinical and experimental data, KiecoltGlaser and Glaser [19] made the following conclusion: ‘considerable evidence has accumulated demonstrating psychosocial or behavioral modification of immune function’. In particular, chronic stress seems to produce longer-term autonomic, endocrinologic and immunologic alterations. The authors consider this relation in two ways: (1) from the etiological perspective (the individual’s susceptibility to developing a somatic illness), and (2) in terms of the effects of therapeutic interventions in cancer patients (improvement of immune function, course of the disease). Finally, another important parameter to be taken into account is the relative downregulation of the immune function in PC patients due to aging (as they are usually middle-aged or older).
Psychiatric Symptoms as Reactive Disorders
In clinical practice, the most common situation we are confronted with is that of a patient with a known cancer at all stages of the course of the disease: from the diagnostic procedure, through the different phases of treatment and
Zilikis/Dervenis
to terminal care. And in the case of PC patients, we are all aware of the very poor prognosis. What we see, then, are the patient’s reactions and ways of coping and adapting – in other terms, of psychic reorganization – to having such a cancer. The way an individual will react to this new life situation depends mainly on his/her personality structure, in other words, the mechanisms of defense that he/she has at his/her disposal. The psychiatric symptoms that will eventually be produced are then ‘reactive disorders’, the most common being anxiety and depressive symptoms. Apart from individual characteristics, any clinician should always consider the role of the supportive systems existing in the patient’s environment. Thus, we move to the psychosocial perspective, including the family, the patient’s other social references and the new agent brought into his/her life by the illness, that is the medical world. In the management of PC patients, all these factors and parameters must be taken into account in a ‘holistic’ approach, with each health professional in charge of the patient’s care finding his/her own specific role while at the same time functioning complementarily with the others. The aim of such a joint effort is to ensure comprehensive care of our patients – the family included – and a quality of life for which the mere palliative or paregoric attitude is not enough.
Conclusions
Although the presence of psychiatric symptoms and psychological distress in general was recognized very early in PC patients, the existing literature shows that a coordinated, systematic study of the problem has not been undertaken yet. Despite the considerable advances in our understanding of the biopsychological mechanisms and processes of this phenomenon, questions still remain unanswered, calling for further research. However, from existing clinical evidence, we may suggest that psychiatric aspects in PC patients could be understood in two ways: (1) considering the role of neurobiological and immunological alterations related to the illness process itself, and (2) taking into account the patient’s personality organization for the production of reactive disorders as part of the overall adaptation to the illness. PC appears to be not only a good example, but, moreover, a paradigm, in that it constitutes a field open to joint research by gastroenterologists, psychiatrists and neuroimmunologists. Such a combined effort will allow for a better understanding of illness as a whole, and for a continuous ‘mutual training’ between clinicians from different specialties, from which both we and our patients can only benefit.
References 1 Holland JC, Rowland JH: Handbook of Psycho-Oncology: Psychological Care for the Patient with Cancer. New York, Oxford University Press, 1990. 2 Yaskin JD: Nervous symptoms at earliest manifestations of carcinoma of the pancreas. JAMA 1931;96:1664–1668. 3 Latter KA, Wilbur DL: Psychic and neurological manifestations of carcinoma of the pancreas. Mayo Clinic Proc 1937;12:457–462. 4 Savage C, Butcher W, Noble D: Psychiatric manifestations in pancreatic disease. J Clin Psychopathol 1952;13:9–16. 5 Perlas AP, Faillace LA: Case reports: Psychiatric manifestations of carcinoma of the pancreas. Am J Psychiatry 1964;121:182. 6 Karlinger W: Psychiatric manifestations of cancer of the pancreas. N Engl J Med 1967;56: 2251–2252. 7 Birnbaum D, Kleesberg J: Carcinoma of the pancreas: A clinical study based on 84 cases. Ann Intern Med 1958;48:1171–1184.
Editorial
8 Fras I, Litin EM, Pearson JS: Comparison of psychiatric symptoms in carcinoma of the pancreas with those in some other intra-abdominal neoplasms. Am J Psychiatry 1967;123:1553– 1562. 9 Klatchko B, Gorzynski JG: A prospective controlled study of depression in patients with pancreatic and other intra-abdominal malignancies; presented at the annual meeting of the American Psychosomatic Society, Denver, March 1982. 10 Holland JCB, Korzun AH, Tross S, Silberfarb P, Perry M, Comis R, Oster M: Comparative psychological disturbance in patients with pancreatic and gastric cancer. Am J Psychiatry 1986;143:982–986. 11 Zabora J, Brintzenhofe Szoc K, Curbow B, Hooker C, Piantadosi S: The prevalence of psychological distress by cancer site. Psychooncology 2001;10:19–28. 12 Passik SD, Roth AJ: Anxiety symptoms and panic attacks preceding pancreatic cancer diagnosis. Psychooncology 1999;8:268–272.
13 Brown JH, Paraskevas F: Cancer and depression: Cancer presenting with depressive illness: An autoimmune disease? Br J Psychiatry 1982; 141:227–232. 14 Pomara NP, Gershon S: Treatment-resistant depression in an elderly patient with pancreatic carcinoma: Case report. J Clin Psychiatry 1984;45:439–440. 15 Olsen DB, Abraham JH: Neuropsychiatric disorders in insulinoma (in Danish). Ugeskr Laeger 1999;161:1420–1421. 16 Marty P: Les mouvements individuels de vie et de mort. Paris, Payot, 1976. 17 Marty P: L’ordre psychosomatique. Paris, Payot, 1980. 18 Marty P: The process of somatization; in Krakowski AJ, Kimball CP (eds): Psychosomatic Medicine. New York, Plenum, 1983, pp 429– 437. 19 Kiecolt-Glaser JK, Glaser R: Psychoneuroimmunology and health consequences: Data and shared mechanisms. Psychosom Med 1995;57: 269–274.
Pancreatology 2003;3:273–275
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