APOS Clinical E-Mail Update #8
23 April 2004

In this Update:

How can we minimize anxiety related to false-positive mammograms?

Barton MB, Morley DS, Moore S, Allen JD. Kleinman KP, Emmons KM, Fletcher SW. Decreasing womenís anxieties after abnormal mammograms: a controlled trial. J National Cancer Institute 2004; 96: 2004; 96: 529-38.

It makes a difference to women if the radiologists read mammograms immediately. Women who had false-positive mammograms were less anxious three weeks after mammography when they already knew that the readings were false-positive if they were treated by radiologists who read films immediately and arranged additional mammography or ultrasound before each woman left the suite. All mammograms were reread by a second radiologist, so that standard of quality assurance was met whether the women were dealt with immediately or not.

This study included interviews 3 weeks after mammography of 2390, 84% of women with abnormal mammograms. Of these 72% knew that they had false positive mammograms by the time of the interview. The structured interview included the Impact of Events Scale, and the Hopkins Symptom Checklist subscales for anxiety and depression. An educational intervention that taught skills to cope with anxiety did not affect the psychological outcome. Those women with false positive mammograms remained more anxious than the others when they were evaluated after 3 months.

Most of the women who had false positive mammograms did not realize that they had had abnormal mammograms when the issues were dealt with immediately. This may have been the reason that they had less anxiety. Those women who were told to come back at 6 six months for reevaluation of minor abnormalities were more anxious at the 3 month interview.

[back to top]

How can we preserve the individual dignity of the cancer patient?

Chochinov HM. Dignity and the eye of the beholder. J Clin Oncol 2004;22:1336-1340.

This case and discussion-- in the section, Art of Oncology: When the tumor is not the target--elaborates on how to help a patient with advanced cancer maintain dignity. Chochinov explains that a patient expressing a wish to die is not typically expressing a request for euthanasia or assisted suicide. Among cancer patients, the patientís desire for death may be seen as a continuous variable. It may vary from a fleeting thought associated with physical suffering or role loss to persistent suicidal thoughts. He notes that hopelessness and depression do not govern the experience of most patients near death. The dignity model, developed empirically by Chochinov, includes illness-related issues, a dignity conserving repertoire, and a social dignity inventory. Qualities related to illness include the level of independence including cognitive acuity and functional capacity. Qualities related to distress involve uncertainty and worry about the dying process. The internal qualities of dignity conserving perspectives include continuity of self, role preservation, generativity/legacy, self-regard, hope--sustained meaning or purpose, a sense of control, and resilience. Practices include living in the moment, maintaining normalcy, and seeking spiritual comfort. Social dignity considers the ability to maintain a measure of privacy, social support, respectful care by others, minimizing the sense of burdening others, and worries about the aftermath of death for others. This model offers a clinical perspective that parses the concept of dignity into elements that can be explored, evaluated, and improved for each patient.

[back to top]

What helps cancer-associated anorexia?

Davis MP, Dreier R, Walsh D, Lagman R, LeGrand SB. Appetite and cancer-associated anorexia: a review. J Clin Oncol 2004;22:1510-1517.

This review will bring readers up to date about the physiology of anorexia and appetite but then put the limited information about cancer-associated anorexia in context. Corticosteroids and synthetic progesterones stimulate appetite and are useful for cancer-associated anorexia, but the most effective timing or dose in the palliative setting is unknown. Cyproheptadine, metoclopramide, nandrolone, and pentoxifylline are not well documented additions to the armamentarium. Hydrazine sulfate does not work.

Appetite is governed by gastric motility, mediated by vagus afferents through the nucleus tractus solitarius to the subjacent dorsal motor nucleus. After absorption, cholecytokinin is released from the duodenum. This feeds back negatively to the nucleus tractus solitarius, slowing motility. The liver releases glucose and insulin, and the adipocytes release leptin, down regulating the neuropetide-Y (NPY) neurons in the arcuate nucleus of the hypothalamus. An ileal phase allows glucagons-like peptide-I to inhibit hypothalamic NPY release and to slow gastric motility.

The arcuate nucleus of the hypothalamus has neurons with NPY and pro-opiomelanocortin (POMC) that are regulated by serotonin and leptin primarily. Leptin, the major appetite suppressant sustains POMC and suppresses NPY. The serotonin system inhibits NPY neuron activity through postsynaptic 5HT1b and 5HT 2c receptors, fostering satiety, but 5HT1a receptors facilitate NPY release.

In cancer-associated anorexia, the assumption is that cytokines like interleukin-1, tumor necrosis factor alpha, ciliary neurotrophic factor, and IL-6 suppress appetite, but there are few data in human cancer patients. The hypotheses that come from tumor-bearing animals are not substantiated in humans.

Corticosteroids, megestrol, and medroxyprogesterone were recommended with level B evidence. Cyproheptadine, dronabinol, metoclopramide, nandrolone, and pentoxyfylline had level C evidence, recommended only in a clinical trial. Melatonin had level B2 evidence. In one open-label, crossover trial of mirtazapine (15 and 30 mg) in 20 cancer patients, patients weights were significantly higher at both week 4 and week 7, independent of dosage 1; this was rated as level D evidence.

1.Theobald DE, Kirsh KL, Holtsclaw E et al. an open-label, crossover trial of mirtazapine in cancer patients with pain and other distressing symptoms. J Pain Symptom Manage 2002;23:442-447.

[back to top]

What are risk factors for depressive symptoms after breast cancer surgery?

Golden-Kreutz DM, Andersen BL. Depressive symptoms after breast cancer surgery: relationships with global, cancer-related, and life event stress. Psycho-oncology 2004;13:211-220.

In looking for predictors of depressive symptoms after breast surgery, Golden-Kreutz and Andersen evaluated the role of three types of stress in 210 women who had surgical treatment for regional breast cancer. They examined the variables of five stressful life events in the previous year, perceptions of global stress, and perception of cancer-related traumatic stress. Global stress perceptions, cancer-related intrusive thoughts, and financial concerns along with the tendency toward negativity (neuroticism) conspired to increase a womanís risk for depressive symptoms. Depressive symptoms were measured by the Center for Epidemiological Studies Depression scale. Neuroticism has been linked with psychological outcomes among cancer patients. Neuroticism in this study was measured by Goldbergís Big-Five factor measure.

This study in the cancer population is interesting to juxtapose to a recent discussion of the predictors of episodes of major depression in a large population of twins. In a study of 7500 twins in a population-based sample, Kendler, Kuhn, and Prescott found that psychosocial adversity interacts both with neuroticism and with gender in the etiology of major depression.1 Neuroticism, female sex, and greater adversity all strongly increased risk for major depression. At low levels of adversity, depression was more common among women, but severe adversity was as likely to cause depression in men as in women. This group has also shown in a subset of this sample that genetic risk factors for major depression moderate the sensitivity to stressful life events. Neuroticism was measured by the Eysenck Personality Questionnaire, and adversity was measured by report of stressful life events like mugging, divorce, major financial problem, serious housing problems, legal problems, loss of confidant, marital problems, serious difficulties at work, and serious events in the social network.

Golden-Kreutz and Andersenís study focuses on the particular stress of breast cancer diagnosis of surgery as it adds to the burden of patients with neuroticism and financial stress.

1. Kendler KS, Kuhn J, Prescott CA. The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression. Am J Psychiatry 2004;161:631-636.

[back to top]

Do families suffer when the patient is delirious?

Morita T, Hirai K, Sakaguchi Y, Tsuneto S, Shima Y. Family-perceived distress from delirium-related symptoms of terminally ill cancer patients. Psychosomatics. 2004; 45:107-113.

Families are upset by the physical restlessness, mood lability, and psychotic symptoms that occur when a patient is delirious. Most bereaved families (n=195), asked in a mailed questionnaire about their experiences with family members, reported that any delirium-related symptom besides sleepiness was distressing or very distressing when they occurred often or very often. The response rate among 300 families who had used the specialized inpatient palliative care services in Japan was 69%. This study corroborates the finding by Breitbart et al 1 that hyperactive delirium causes a great deal of stress for family members.

1.Breitbart W, Gibson C, Tremblay a: the delirium experience: delirium recall and delirium-related distress in hospitalized patients with cancer, their spouse/caregivers, and their nurses. Psychosomatics. 2002;43:183-94.

[back to top]

How do we identify patients with depressive disorder after treatment for head and neck cancer?

Katz MR, Kopek N, Waldron J, Devins GM, Tomlinson G. Screening for depression in head and neck cancer. Psycho-oncology 2004;13:269-280.

This study evaluates the number of patients treated for head and neck cancer who have depressive disorder one month after the radiation treatment. It offers practical data on which screening tool would be most effective for identifying those depressed. The Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale (HADS), and the Center for Epidemiological Studies-Depression (CES-D) scale were all used for screening; and the Schedule for Affective Disorders and Schizophrenia (SADS) structured interview was used as the gold standard. The prevalence of major and minor depression was 20%. They determined that all of the screening instruments were highly accurate. No cases of major depression would have been missed by any of the instruments tested.

This study offers practical guidance for those caring for head and neck cancer patients. These patients have a high rate of alcohol and nicotine abuse and may suffer changes in facial appearance, difficulty swallowing, and loss of voice. Major depressive disorder is treatable. The current risk of major depression in former drinkers is increased 4-fold. 1

A recent meta-analysis suggested that antidepressant medication exerts a modest beneficial effect for patients with combined depressive- and substance-use disorder, but it is not a stand alone treatment; concurrent treatment targeting addiction is also warranted. 2

One month after the completion of radiation treatment is a convenient time to assess depression and to foster treatment that will make recovery easier. The authors have shown that a variety of rapid screening techniques can identify the cases.

1. Hasin DS, Grant BF. Major depression in 6050 former drinkers: association with past alcohol dependence. Arch Gen Psychiatry 59:794-800, 2002.

2. Nunes EV, Levin FR. Treatment of depression in patients with alcohol or other drug dependence: A meta-analysis. JAMA 2004; 291: 1887-1896.

[back to top]

What are common pitfalls in assessment of decision making capacity?

Ganzini L, Ladislav V, Nelson W, Derse A. Pitfalls in assessment of decision-making capacity. Psychosomatics 2003; 44: 237-243.

This study did not focus on cancer patients but did consider what happened when providers called the psychiatrist or psychologist to ask about capacity in older patients. The authors asked 395 consultation-liaison psychiatrists, geriatricians, and geriatric psychologists what they thought about 23 potential pitfalls and misunderstandings by clinicians who refer patients for assessment of decision-making capacity. The most important pitfall was the tendency for health care practitioners to assume that a patient who lacks capacity for one type of medical decision also lacks capacity for all medical decisions. Other major pitfalls were: 2) the practitioner does not understand that capacity or incapacity is not all or nothing, but specific to a decision. 3) The practitioner confuses legal competence, as decided by a formal judicial proceeding, with clinical determination of decision-making capacity. 4) Practitioner fails to ensure that the patient has been given relevant and consistent information about the proposed treatment before making a decision. 5) As long as a patient agrees with the practitionerís health care recommendations, the practitioner fails to consider that the patient may lack capacity for decisions. 6) When evaluating a patientís ability to return to independent living, the practitioner assesses only what the patient says and fails to have the patientís functional abilities and living situation evaluated. The authors enumerate other pitfalls and show that it is common for clinicians to misunderstand the relationship between mental illness, cognitive ability, and capacity.

[back to top]

Is the toxicity of interferon and appropriate dosing of antidepressant medication related to the ability of interferon to inhibit liver enzymes?

Islam M, Frye RF, Richards TJ, Sbeitan I, Donnelly SS, Glue P, Agarwala SS, Kirkwood JM. Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs. Clinical Cancer Research 2002;8:2480-2487.

High dose interferon-alfa 2b, the standard therapy for high-risk melanoma, suppresses CYP enzymes. There is a correlation of CYP inhibition and occurrence of fever and neurological toxicity. These authors studied 17 patients. CYP 1A2 and 2D6 were significantly inhibited immediately after the first interferon dose, whereas significant inhibition of CYP2C19 was detected first at day 26. Drugs metabolized by 2D6 include fluoxetine, haloperidol, codeine, nortriptyline, paroxetine, risperidone, tramadol, amitriptyline, desipramine, doxepin, imipramine, perphenazine, propranolol, thioridazine, and timolol. Drugs metabolized by 2C19 include clomipramine, diazepam, omeprazole, venlafaxine. Since interferon often causes depression, it is important to note that antidepressants may be metabolized more slowly during treatment with interferon. Antidepressant medication has been useful for patients on this interferon regimen, but a lower dose may have a stronger effect.

[back to top]


Donna B. Greenberg, MD, Associate Professor of Psychiatry at Harvard Medical School and Psychiatric Consultant in the Massachusetts General Hospital Cancer Center, Dana Farber Partners Cancer Care