APOS Clinical E-Mail Update #9
3 June 2004

In this Update:

Do patients with a history of hospitalization for depression have a poorer breast cancer prognosis?

Hjerl K, Andersen EW, Keiding N, Henning T et al.  Depression as a prognostic factor for breast cancer mortality.  Psychosomatics 2003;44:24-30. 

If you read the title of this article, you may think that negative thoughts make breast cancer cells grow.  This is not a fair conclusion from this study. 

These authors brought together the power of two Danish case registries, the Danish Psychiatric Case Register and the records of the Danish Breast Cancer Cooperation Group.  They were able to study more than 20,000 women who had been enrolled in clinical trials for breast cancer treatment.  These women were from 23 to 70 with a mean age of 55.  Depression was defined as all affective disorders and anxiety disorders, and patients were identified whose psychiatric illness had led to hospital admission.

The first psychiatric admission for affective disorder occurred three months or more before the diagnosis of breast cancer in 2.8% of the women.  The first episode of affective disorder leading to hospitalization occurred after the diagnosis of breast cancer in 1.2% of the early-stage breast cancer patients and 0.7% of late-stage patients.  For late-stage breast cancer patients preoperative depression was associated with a significantly higher relative risk of mortality.  A similar trend was seen for early-stage patients.  This effect was slightly more pronounced in women with bipolar illness.

The authors have identified a group of women with both psychiatric disorder and breast cancer.  These women were included in cancer protocols as often as women without depressive disorder, but the researchers could not assess co-morbid substance abuse, lifestyle, socioeconomic factors, smoking, cognitive dysfunction, and non-compliance.  They had no information on psychiatric treatment.  They have shown that patients with affective disorder, severe enough to be hospitalized, have a higher mortality from breast cancer than those with no psychiatric hospital admission.  We know that mental illness is bad for physical health generally, but we do not know what other factors in psychiatric care or comorbidity can explain this phenomenon.  The implication overall is that patients with depressive disorder have worse outcome in breast cancer; seeing to it that they get state of the art psychiatric care becomes important to the overall cancer outcome.

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What should you know about treating kids with terminal illness?

Himelstein BP, Hilden JM, Boldt AM, Weissman D.  Pediatric palliative care.  N Engl J Med 2004;350: 1752-62. 

This is a very effective review article of the role of palliative care for children.  The review incorporates key tables that are practical and useful for teaching.  These include, conditions appropriate for pediatric palliative care, essential elements in the approach, medications used for common symptoms, developmental changes in death concepts and spirituality in children, elements of complete developmental understanding of death, and myths and realities of childhood grief.  It is a succinct and effective review.

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Do young patients with bone sarcoma do worse with amputation than limb salvage?

Magarajan R, Neglia JP, Clohisy DR, Robison LL.  Limb salvage and amputation in survivors for pediatric lower-extremity bone tumors: what are the long-term implications? J Clin Oncol 2002;20:4493-4501. 

This study reviews amputation, rotationplasty, and lower-extremity limb sparing techniques used as primary treatment for osteosarcoma and other bone tumors in children, adolescents, and young adults.  It brings together the studies that compare amputation and limb salvage in terms of quality of life and function.  Survival is equivalent with amputations or limb salvage, but complications occur more frequently in limb salvage.  Despite these complications, the authors conclude that improvement in surgical techniques and prostheses and an optimistic functional outcome have made limb salvage the procedure of choice when it can be performed with oncological safety.  They highlight the interplay of physical and psychological aspects of functions: acceptance of the procedure, self-consciousness, and motivation.  They note that more subtle and informative information about the value of surgical options may come from prospective studies that should extend 10-15 years.

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Do fluctuations in ovarian function affect mood?

Daly RC, Danaceau MA, Rubinow DR, Schmidt PJ.  Concordant restoration of ovarian function and mood in perimenopausal depression.  Am J Psychiatry 2003;160:1842-1846. 

The relationship of mood to changes in ovarian function are important matters to understand if we are to better understand the effect of anti-cancer treatment for breast cancer patients.  This study continues an exploration of mood changes and pituaitary-ovarian-axis function in women exhibiting perimenopausal depression.  Estradiol has recently been shown to improve mood in perimenopausal women who are depressed.  Estradiol is not an option for women with breast cancer.  At a menopause clinic, 110 women offered a mood report and a follicle-stimulating hormone plasma level (FSH) level at baseline.  Of these women 18 reported better mood at week 6.  This improvement was associated with a significant decrease in FSH.  Those patients whose FSH level dropped by 50% also had an improvement in mood in 17 of 23 women.  The authors emphasize that women with endocrine-related mood disorders have different responses to the same intervention.  Individual variation is significant.  In breast cancer patients, chemotherapy may suppress ovarian function temporarily or permanently.  Anti-estrogens may further remove the estrogen directed at the brain.  As women encounter the challenges of the diagnosis and the burdens of treatment, they are likely enduring variable withdrawal of estrogen and fluctuating FSH levels.  For some of those women, that hormonal variability is likely to be associated with depressed mood.

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What keeps the breast cancer patient up at night?

Savard J, Davidson JR, Ivers H, et al.  The association between nocturnal hot flashes and sleep in breast cancer survivors.  J Pain Symp Manage 2004;27:513-522. 

Insomnia during breast cancer treatment could be related to clinical depression or the stress of chemotherapy, but these authors have highlighted the relationship between insomnia and hot flashes in 24 women who had completed treatment for localized breast cancer.  All were receiving cognitive-behavioral treatment for insomnia.  During the 10 minutes around hot flashes, women spent more time awake and had more changes to lighter sleep stages than during other 10 minute periods during the night.  Nights with hot flashes had longer REM latency than nights without hot flashes.  Insomnia in breast cancer patients may be a sign of estrogen withdrawal.  In the categorical diagnosis of clinical depression, the symptom of insomnia may be related to menopausal changes; on the other hand, low mood may be an associated factor in hormonal insufficiency.  Clinically, it is helpful to explain to a patient that insomnia may be related to hormonal change and can be alleviated by specific medical treatments for sleep or hot flashes.  Sometimes, just the understanding that insomnia goes with hormonal change allows the patient a non-judgmental explanation for difficulty with sleep.

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Do topical opioids have a role for mouth ulcers?

Gallagher R.  Methadone mouthwash for the management of oral ulcer pain.  J Pain Symp Manage 2004;27:390-391. 

Oral ulcers have been a distinct pain problem in cancer treatment.  Beyond prevention of infection, hydration, and good oral hygiene, Gallagher suggests that this intermittent incident pain can be alleviated by affecting the opioid receptors of the peripheral pharynx tissue with topically–applied opiate.  The pain of an oral ulcer from Behcet’s disease led Gallagher’s patient to garble his speech, eat only pureed foods, and lose weight.  He slept only in short naps and had severe pain when his tongue touched his teeth.  A magic mouthwash included methadone powder at
1 mg/ml.  In addition, the mouthwash had 120 ml diphenhydramine liquid 2.5 mg/ml, 30 ml nystatin oral suspension, 750 mg tetracycline, and dexamethasone 4 mg to a volume of 200 ml distilled water.  The effectiveness of the mouthwash dropped from 75% to 40% when the methadone powder was removed.  With 5 ml solution 10-14 times per day, the author judged that 17% was absorbed.  Serum methadone level was determined.

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How long does it take to recover from hematopoietic cell transplantation after leukemia or lymphoma?

Syrjala KL, Langer SL, Abrams JR, Stoerer B, Sanders JE, Flowers ME, Martin PJ.  Recovery and long-term function after hematopoietic cell transplantation for leukemia or lymphoma.  J Amer Med Assoc 2004; 291:2335-2343. 

This study from the Fred Hutchinson Cancer Research Center prospectively studied 99 of 319 long-term survivors.  Previous studies have been cross-sectional, and this study offers a clearer perspective to patients.  The authors assessed patients at baseline, 90 days, and 3 and 5 years.  A majority (84%) of those who had no recurrence of malignancy returned to work.  Slower physical recovery was associated with more depression before the transplantation.  Depression was measured prospectively by the Beck Depression Inventory.  Risk factors for depression after transplantation were graft-vs-host disease, less social support, and female gender.  Their results suggest that interventions that improve care for depression, occupational function, and social support may hasten recovery.  Of note, those patients alive at 3 and 5 years who were older, receiving allogeneic transplants or total body irradiation, and those with higher-risk diagnoses and disease stages had the same long-term quality of life as those patients with better medical prognoses.  The authors suggest that psychological and rehabilitative programs may be important for these patients and that those at high risk can be identified early on.

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What do we know about "chemo" brain?

Tannock IF, Ahles TA, Ganz PA, van Dam, FS.  Cognitive impairment associated with chemotherapy for cancer: report of a workshop.  J Clin Oncol 2004; 22:2233-2239. 

This is a report of the workshop in Banff, Alberta, Canada, in April 2003, at the meeting of the Canadian Psychooncology Society that brought together many of the researchers who had tried to understand “chemo brain”.  They summarize studies of cognitive impairment in patients receiving chemotherapy and conclude that cognitive deficits are often subtle and occur in a range of cognitive functions.  The mechanism is unknown.  Some times there are durable deficits.  Since there were no consistent findings, these researchers emphasized the need for longitudinal studies and studies with a concurrent comparison to patients who are not receiving chemotherapy.  It would be important to understand the discrepancy between the report of cognitive dysfunction and the difficulty in documenting objective results.  They noted that breast cancer patients are simultaneously faced with hormonal changes as a part of treatment; therefore, the relation between cognitive impairment and chemotherapy may be better assessed in men and women with another condition.  Animal models and imaging techniques may be useful in the future.

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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