Bone marrow chromosome abnormalities in breast cancer in patients following adjuvant chemotherapy.

Two patients developed acute bone marrow cancer following mastectomy and institution of alkylating agents as adjuvant chemotherapy. An aneuploid condition was observed in both cases, along with involvement of chromosomes 11 and 12 in structural rearrangements. Subsequent studies of 18 patients who had or had not received such therapy showed no evidence of chromosomal aberrations. However, the long-term effect of adjuvant chemotherapy in cancer patients is still of concern until additional information becomes available.

Doxorubicin-containing regimens for the treatment of stage II breast cancer: The National Surgical Adjuvant Breast and Bowel Project experience.

Despite numerous reports of findings obtained following the use of doxorubicin (Adriamycin [A]; Adria Laboratories, Columbus, OH) for the postoperative treatment of patients with primary breast cancer and positive axillary nodes, no clear consensus exists regarding its worth when used in that setting. In June 1981, the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented two randomized clinical trials aimed at evaluating the worth of doxorubicin when administered in conjunction with melphalan (L-PAM) and fluorouracil (5-FU) (PF). A prior NSABP study identified cohorts of patients who did or did not benefit from tamoxifen (TAM, T) when used with chemotherapy. That information was employed in the design of the present studies. Women considered responsive to TAM (1,106) were randomized between PFT and PAFT, and those nonresponsive to TAM (707) were randomized between PF and PAF. Findings through 6 years of follow-up (mean duration of potential time on study, 64 months and 63 months, respectively) indicate that non-TAM-responsive patients who received PAF had a significantly better disease-free survival (DFS) (P = .003) and survival (P = .05) than did those receiving PF. By contrast, there was no significant difference in DFS (P = .6) or survival (P = .7) between PFT- and PAFT-treated patients. No disparity in the amount of drug received, whether related to the median amount or to dose-intensity, is present to account for the difference in findings between the studies. Aside from alopecia and emesis, the toxicity from the doxorubicin-containing regimens was similar to those in which doxorubicin was omitted. Cardiomyopathy was not a significant finding; there were no deaths from cardiac toxicity. The incidence of arterial and venous complications in patients receiving TAM was less than reported by others.

Increased intensification and total dose of cyclophosphamide in a doxorubicin-cyclophosphamide regimen for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-22.

PURPOSE: The National Surgical Adjuvant Breast and Bowel Project (NSABP) initiated a randomized trial (B-22) to determine if intensifying but maintaining the total dose of cyclophosphamide (Cytoxan, Bristol-Myers Squibb Oncology, Princeton, NJ) in a doxorubicin (Adriamycin, Pharmacia, Kalamazoo, MI)-cyclophosphamide combination (AC), or if intensifying and increasing the total dose of cyclophosphamide improves the outcome of women with primary breast cancer and positive axillary nodes. PATIENTS AND METHODS: Patients (N = 2,305) were randomized to receive either four courses of standard AC therapy (group 1); intensified therapy, in which the same total dose of cyclophosphamide was administered in two courses (group 2); or intensified and increased therapy, in which the total dose of cyclophosphamide was doubled (group 3). The dose and intensity of doxorubicin were similar in all groups. Disease-free survival (DFS) and overall survival were determined using life-table estimates. RESULTS: There was no significant difference in DFS (P = .30) or overall survival (P = .95) among the groups through 5 years. At 5 years, the DFS of women in group 1 was similar to that of women in group 2 (62% v 60%, respectively; P = .43) and to that of women in group 3 (62% v 64%, respectively; P = .59). The 5-year survival of women in group 1 was similar to that of women in group 2 (78% v 77%, respectively; P = .86) and to that of women in group 3 (78% v 77%, respectively; P = .82). Grade 4 toxicity increased in groups 2 and 3. Failure to note a difference in outcome among the groups was unrelated to either differences in amount and intensity of cyclophosphamide or to dose delays and intervals between courses of therapy. CONCLUSION: Intensifying or intensifying and increasing the total dose of cyclophosphamide failed to significantly improve either DFS or overall survival in any group. It was concluded that, outside of a clinical trial, dose-intensification of cyclophosphamide in an AC combination represents inappropriate therapy for women with primary breast cancer.

Effect of benzopyranoperidine, a delta-9-THC congener, on pain.

In a double-blind, 5-way crossover designed study, single doses of placebo, 2 doses of codeine sulfate (60 and 120 mg), and 2 doses of benzopyranoperidine (2 and 4 mg) were administered orally to 35 patients who required analgesics for chronic pain due to malignancies. Benzopyranopyridine is an analogue of delta-9-tetrahydrocannabinol and was chosen on the basis of its sedative, hypnotic, and analgesic properties in animals. Pain relief scores indicated a degree of relief of clinical significance with 120 mg of codeine but no consistent difference between placebo and any other active agent. On the basis of the data, bezopyranoperidine (2 or 4 mg) is not as effective as codeine (120 mg or 60 mg) and not more effective than placebo in relieving pain due to cancer; indeed, pain perception appeared to be augmented by both doses.

Appraisal of codeine as an analgesic in older patients.

In an investigation of a new oral analgesic agent, codeine was chosen as the reference drug because of its established reputation as an effective agent for the relief of pain. Thirty-five patients with cancer pain were studied. Their average age was 58 years, During a 5-day hospital stay they received, on each of three days, either codeine (120 mg or 60 mg) or placebo. At hourly intervals after ingestion the nurse observer collected data on pain intensity and the degree of pain relief, and the patients independently charted the hourly intensity. Statistical analysis failed to show any significant superiority of either dose of codeine over placebo. Moreover, codeine is known to have a constipating effect. Re-appraisal of the value of codeine as an analgesic agent in elderly patients seems justified.

The changing attitudes of physicians toward prolonging life.

This follow-up survey of physicians' attitudes and practices reveals a changing approach toward the care of terminal patients. It shows that: 1) communication with dying patients is becoming more open, 2) support for the omission of life-prolonging treatments is increasing, and 3) opposition to the use of death-hastening measures remains strong. It indicates that the physician's experience with terminal patients and the setting of his practice influence his attitude towards these patients and the approach to treatment.

Melanoma of skin of the breast: therapeutic considerations based on six cases.

Melanomas of the skin of the breast are uncommon lesions which are amenable to cure with standard mastectomy techniques, even when lymphatic spread has occurred. Of six patients treated at the University of Iowa, two have died of metastatic melanoma, one treated by wide excision and subsequent axillary dissection and the other by radical mastectomy initially. Of the remaining patients, one with positive axillary nodes at the time of mastectomy died 28 years following operation of unrelated causes, one with axillary nodes involved is 5 years without evidence of recurrence, and two who have been followed for less than 2 years, are without evidence of recurrent disease in spite of having had positive nodes at the time of initial treatment. All six patients had had pigmented lesions of the skin of the breast for many years, suggesting that such lesions in this location should be considered premalignant.

An analysis of male and female breast cancer treatment and survival among demographically identical pairs of patients.

BACKGROUND: Male breast cancer is rare, and there are no large comparative studies to guide treatment. We used National Cancer Data Base data on 4755 men and 624,174 women who had breast cancer (1985-1994) to identify equivalent groups of male and female breast cancer patients. METHODS: For each man with breast cancer, the next woman treated at the same hospital was sought who matched the man's age (within 5 years), ethnicity, income category, and stage. We identified 3627 closely matched pairs of male and female patients with breast cancer. RESULTS: Men were more likely to be treated with mastectomy (modified radical, 65% of men versus 55.1% of women; radical, 2.5% of men versus 0.9% of women; simple, 7.6% of men versus 3.4% of women; P <.001), and more likely to receive radiation therapy after mastectomy (men, 29%; women, 11%; P <.001). Men treated with lumpectomy were less likely to receive radiation therapy (men, 54%; women, 68%; P <. 001). Men were also less likely to receive chemotherapy (26.7% of men versus 40.6% of women; P <. 001) after any surgical treatment. CONCLUSIONS: This large comparative study is the first to detail stage-specific differences in contemporary treatment strategies for highly comparable groups of men and women treated for breast cancer. Further studies of male breast cancer should focus on identifying prognostic factors and defining optimal therapy.

Iatrogenic liver abscesses. A complication of hepatic artery ligation for tumor.

The use of hepatic artery ligation, with or without placement of an indwelling infusion catheter for the instillation of chemotherapy, became widely employed in the late 1960s. This was a natural outgrowth of observations that it was reasonably well tolerated in man if certain precautions were followed and that tumors in the liver, whether primary or metastatic, received the major portion of their blood supply by that vessel. As tumor necrosis following ligation was the anticipated result, it followed that undrained collections of nonviable tumor might well be expected to develop in a certain number of patients and that such collections would form intrahepatic abscesses. It appears that development of the complication does not adversely affect the result of the procedure, and this must certainly only be true because of recognition and proper therapy directed to the complication.

Hemicorporectomy for intractable decubitus ulcers.

A hemicorporectomy was successfully employed for control of intractable decubitus ulcers, osteomyelitis, and low-grade epidermoid cancer in a 55-year-old man marked reduction in pulmonary functions. Strict attention to postoperative fluid balance was associated with a smooth convalescence. The operation may be more applicable to paraplegic patients with intractable pelvic decubiti than to those with advanced pelvic tumors. In view of the increased number of paraplegics who may be at risk for developing this problem, more frequent consideration of the procedure seems warranted.

Handling of cytotoxic drugs by healthcare workers. A review of the risks of exposure.

Increasing utilisation of chemotherapeutic agents in treating patients with malignancy has led to the potential for widespread exposure of healthcare workers who come into contact with patients or these agents in the work place. Unfortunately, these drugs are toxic to both the abnormal and normal somatic cell. This occurs in the patient, and is also likely to affect any individual exposed. There appear to be widely divergent opinions concerning the extent of hazard of coming into contact with these agents, in spite of which caution and minimising exposure risk seems only prudent and appropriate.

Peritoneal venous shunting for the treatment of lymphatic ascites following retroperitoneal lymph node dissection.

We report a case of refractory lymphatic ascites following retroperitoneal lymph node dissection and venacavectomy. Placement of a Denver peritoneal venous shunt resulted in resolution of the ascites and marked improvement in the patient's nutritional parameters. Shunt occlusion 2 months following placement demonstrated no recurrence of the ascites. This technique may prove useful in the management of lymphatic ascites associated with radical retroperitoneal surgery.

Neurosarcomatous malignant melanoma arising in a neuroid giant congenital melanocytic nevus.

We report a case of neuroid giant congenital melanocytic nevus (GCMN) in which a malignant schwannomalike tumor developed. Literature review reveals that neurosarcomatous differentiation occurs among malignant tumors arising in GCMNs, apparently with greater incidence in those GCMNs showing benign neuroid differentiation. Although the differences between neuroid melanocytes and Schwann's cells may be more conceptual than real, we believe that the current tumor arising within a melanocytic nevus is likely of neuroid melanocytic origin and best designated as neurosarcomatous malignant melanoma.

Surgical management of complications of radiation-injured gut.

Radiation-injured bowel has been diagnosed in 5.1 per cent of 1,824 patients receiving pelvic or abdominal radiotherapy over the past ten years. Surgical intervention to manage these complications was required in 35 per cent. The type of procedure employed for large and small bowel complications has been evaluated to define guidelines for future therapy.

Diet intervention methods to reduce fat intake: nutrient and food group composition of self-selected low-fat diets.

A multicentered pilot study was conducted to test an intervention protocol designed to reduce fat intake to 15% of energy intake. Eligible subjects were postmenopausal women with stage II breast cancer whose baseline fat intake was more than 30% of energy intake. The low-fat diet intervention protocol consisted of bi-weekly individual counseling sessions with emphasis on substitution of lower-fat foods for high-fat foods and maintenance of nutritional adequacy. Nutrient intakes were calculated from 4-day food records collected at baseline and after 3 months of diet intervention. Mean daily fat intake for the 17 patients on the low-fat diet dropped significantly from 38.4 +/- 4.3% of energy intake at baseline to 22.8 +/- 7.8% at 3 months (p less than .001). A 25% reduction in mean energy intake, from 1,840 +/- 419 kcal at baseline to 1,365 +/- 291 kcal at 3 months, was accompanied by significant increases in protein and carbohydrate as percent of energy intake. A mean weight loss of 2.8 kg and a 7.7% reduction in serum cholesterol were observed; both changes were significant at the p less than .01 level. Absolute intakes of zinc and magnesium were significantly reduced. However, mean intake on the low-fat diet for 14 vitamins and minerals, including zinc and magnesium, exceeded two-thirds of the 1989 Recommended Dietary Allowances (RDAs). When expressed as nutrient density (i.e., amount of nutrient per 1,000 kcal), increases were observed for all micronutrients. These results support the hypothesis that a nutritionally adequate low-fat diet can be successfully implemented in a highly motivated, free-living population.

Subacute vincristine toxicity following five consecutive daily doses.

Vincristine (VCR) is commonly included in combinational chemotherapy regimens because of its synergy with a variety of other active agents, as well as its sparing of the hematopoietic system. While acute toxicity is not infrequently reported, a recent experience in an adult who received five consecutive daily doses of VCR (1.0 mg/m2) in conjunction with two other drugs led to a sequence of life-threatening toxicities which were not obviously ameliorated by folinic acid rescue as has been recently advocated. The increasing administration of protocol chemotherapy by practitioners in the community, who may not be especially familiar with the particular agents in a given regimen, suggests such errors may become more common.

Phase II study of dibromodulcitol and BCNU in metastatic malignant melanoma.

Dibromodulcitol (DBD) and BCNU were administered to 20 patients with metastatic malignant melanoma who had not received prior chemotherapy. One complete and three partial responses were noted; duration of response was short. Dose limiting toxicity was thrombocytopenia. DBD and BCNU do not appear to improve response over single agent therapy for disseminated melanoma.

Chemotherapeutic toxicity--the relationship between patients' pretreatment expectations and posttreatment results.

Patients receiving the same cancer chemotherapy regimens exhibit a highly variable incidence of toxic side effects. We studied 56 patients about to receive chemotherapy for the first time to determine whether their expectations of individual side effects were associated with the frequency and severity of the toxicity that they subsequently experienced. Patients completed a self-report questionnaire containing a list of 16 potential toxicities, asking them to indicate how certain they were of experiencing or not experiencing each. Prior to their third treatment, patients again completed a self-report scale indicating the incidence and severity of each side effect experienced. The frequency of actual side effects was much greater than patients anticipated. The most commonly reported side effects were tiredness, changes in appetite or taste, nervousness, and nausea. Patients' expectations failed to predict the occurrence or severity of the experience of common side effects. Anxiety levels and meaning attributed to side effects also were not associated with side effects experienced. Although psychological factors may play a role, it is likely that unique physiologic parameters account primarily for the variable and unpredictable relationship between chemotherapeutic agents and the side effects they induce.

Duodenal trauma in the rural setting.

During the past 15 years, 21 patients with duodenal injuries were treated at the University of Iowa Hospitals and Clinics. The major cause of injury (66.6%) was blunt abdominal trauma. Eighteen patients (85.7%) underwent celiotomy. Only one patient (4.7%) had an isolated duodenal injury. In most cases, a careful exploration of the periduodenal area and lesser sac was necessary to diagnose and treat the injury. No one specific procedure was used in these patients. The use of Penrose drains did not prevent abscess formation in three of nine patients. Overall mortality was 23.8 per cent, but most deaths were related to other serious injuries. Only one death (4.7%) was directly related to the duodenal injury. In the rural setting, duodenal injuries are rare, but when they occur they are frequently the result of blunt trauma. These injuries are commonly associated with other obvious problems and may be easily overlooked. Because the preoperative diagnosis is difficult, careful intraoperative examination of the entire duodenum is mandatory.

Male breast carcinoma.

Fifty men with primary breast carcinoma were seen between the years 1938 and 1983 at the University of Iowa Hospitals and Clinics. In most patients, there was a significant delay between the onset of symptoms and seeking medical advice (mean, 21 months; range, 1-156). The vast majority of patients were treated by simple, modified radical, or radical mastectomy. Ten patients underwent incisional or excisional biopsy with or without radiation because of locally advanced disease or distant metastases. Survival was comparable in the groups of patients treated with simple mastectomy (mean, 70 months), modified radical mastectomy (mean, 61 months), and radical mastectomy (mean, 78 months). Local recurrence occurred in 25 per cent of all patients, and this rate was not dependent on the operation performed. The data suggest that modified radical mastectomy is adequate therapy for local control and staging of the disease without reducing survival from that observed after radical mastectomy.