Survival analyses of breast cancer patients--the Shaukat Khanum Memorial experience.

Seven hundred subjects with breast cancer malignancies were followed up in time from December 1994 to December 2002 to determine survival distributions between sub-groups of breast cancer patients who had undergone surgical resection of the tumor followed by adjuvant treatment. Tumor size, nodal status, and Estrogen Receptor (ER) status at the time of presentation were ascertained. Tumors were classified according to the TNM system of the American Joint Committee on Cancer (AJCC), sixth edition, and grouped into T1/T2 and T3/T4; lymph nodes were categorized as N0 (node-negative) and N1, N2, and N3 combined (node-positive). The endpoint of interest for disease-free survival was relapse, and for overall survival, it was death. The Wilcoxon statistics for testing the equality of disease-free survival distributions between groups of patients with tumor size greater than 5 versus less than or equal to 5 cm, node-positive versus node-negative, and ER-positive versus ER-negative were found to be statistically significant (p < 0.05). For overall survival, substantial differences were found between groups of patients stratified according to tumor diameter and nodal involvement, but none for ER status.

Prospective randomized comparison of tropisetron with and without dexamethasone against high-dose metoclopramide in prophylaxis of acute and delayed cisplatin-induced nausea and vomiting.

Several studies have confirmed the efficacy of high-dose metoclopramide and, more recently, serotonin antagonists, with and without dexamethasone, in the prophylaxis of cisplatin-induced nausea and vomiting. Most of these trials have been reported from Western countries. There is little or no information about the efficacy and tolerability of these agents in ethnic groups in other countries. Furthermore, many patients in the developing countries cannot afford serotonin antagonists. The result is a critical need to evaluate these agents and justify their increasingly common use. The authors performed a prospective randomized trial to compare the efficacy and tolerability of tropisetron with and without dexamethasone against high-dose metoclopramide cocktail in patients receiving a uniform dose of cisplatin (100 mg/m2). Metoclopramide 2 mg/kg was combined with clemastine, dexamethasone, and lorazepam. These drugs were initially repeated at short intervals and subsequently given in the oral form for the next 5 days. Tropisetron 5 mg was administered intravenously 15 minutes immediately before cisplatin therapy and followed up with oral therapy for 5 days. The third group received the same doses of tropisetron along with dexamethasone before cisplatin and twice daily thereafter. The authors randomized 301 episodes. The patient characteristics were well balanced between the three groups. Acute nausea and vomiting were completely prevented in almost two thirds of patients receiving metoclopramide and tropisetron plus dexamethasone. These results are significantly superior to those of tropisetron alone (p < 0.01). Similarly, delayed nausea and vomiting were significantly better controlled with metoclopramdie cocktail and tropisetron plus dexamethasone than with tropisetron alone. Side effects were generally mild; however, they were more frequent with metoclopramide. The authors conclude that metoclopramide-based combination antiemetic therapy continues to be a cheaper alternative to serotonin antagonists and equally effective. Metoclopramide-based therapy, however, is more labor intensive, and issues related to administrative errors, side effects, and compliance gain increasing importance. The identification of persons at a higher risk for metoclopramide-induced side effects may help minimize the unacceptable consequences of therapy.

Effect of subcutaneous injection of granulocyte-macrophage colony stimulating factor (GM-CSF) on healing of chronic refractory wounds.

OBJECTIVE: To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on healing of chronic wounds. DESIGN: Prospective open study. SETTING: 1 cancer hospital and 2 University hospitals, Pakistan. SUBJECTS: 35 patients with chronic wounds (duration 3 months or longer) that had not responded to standard treatment. Patients with malignant ulcers were excluded. INTERVENTION: GM-CSF 10 microg/cm2 was injected subcutaneously along the edges and base of the wound. The treatment was given only once and patients were followed weekly for a minimum of six weeks. MAIN OUTCOME MEASURES: Changes in size, shape, depth, edges and base of the wound, amount and quality of the granulation tissue, and type of discharge. RESULTS: Six patients were excluded from the analysis, 4 who died early of underlying disease and were not evaluable, and 2 who were excluded when histological examination of the wound showed that it was malignant. Although various types of wounds were studied, most (n = 10, 34%) were postoperative. 23 of the wounds were over 2 cm in diameter (mean 4.8 x 4.6 cm) with thin granulation tissue, and almost half were infected. Nine of the 29 wounds healed completely within six weeks while another 11 decreased in size by more than 50%; 7 patients responded slightly. Only two wounds showed no evidence of healing during the observation period. More than half of the 20 wounds that responded had healed by three weeks. Response did not correlate with any clinical variable including the presence of infection. Toxicity was negligible. CONCLUSIONS: We conclude that subcutaneous injection of a single dose of GM-CSF may induce healing in refractory chronic wounds. Trials are necessary to validate these initial observations and to decide the optimal dose and route, and whether any additional benefit may be derived from repeated injections.

A randomized comparison of fluconazole with amphotericin B as empiric anti-fungal agents in cancer patients with prolonged fever and neutropenia.

PURPOSE: Several studies have documented the efficacy of amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia. Amphotericin, however, is a toxic drug. Fluconazole has broad-spectrum antifungal activity with an excellent safety profile. Although prophylactic use of fluconazole is widespread, its efficacy as an empiric antifungal agent has not been extensively investigated. PATIENTS AND METHODS: We randomly assigned 106 patients with absolute neutropenia (< or = 500 cells microL) and persistent fever of undetermined origin (> 38 degrees C) despite 1 week of broad-spectrum antibiotic therapy to receive either fluconazole 400 mg orally daily or amphotericin B 0.5 mg/kg/day. Patients with obvious invasive fungal infections were excluded, as were those with abnormal renal or hepatic function. Success was defined as defervescence with the initially assigned antifungal regimen without development of clinically evident invasive fungal infection. RESULTS: Six patients were excluded from the analysis, mostly because they did not have severe neutropenia. Forty-eight patients received amphotericin B, and 52 received fluconazole. Baseline clinical characteristics and laboratory parameters as well as duration of neutropenia (7.7 versus 6.9 days), duration of fever (7.8 versus 8.1 days), and duration of hospitalization (10.4 versus 8.3 days) were similar between those receiving amphotericin and fluconazole. Treatment success rates and mortality rates were similar in the two groups: 22 (46%) patients in the amphotericin group and 29 (56%) patients in the fluconazole group responded successfully to therapy (P = 0.3), whereas 16 (33%) patients in the amphotericin group and 14 (27%) patients in the fluconazole group died during hospitalization (P = 0.5). Adverse events such as chills and fever (4 versus 1), bronchospasm (2 versus none), severe hypokalemia (25 versus 12) and nephrotoxicity (9 versus 3) were more frequently observed in patients receiving amphotericin. Adverse prognostic factors included prolonged duration of neutropenia and pneumonia. CONCLUSIONS: These results suggest that fluconazole is an equally effective but less toxic alternative to amphotericin B as empiric antifungal therapy in cancer patients with prolonged fever and neutropenia.

Immuno-histochemical analysis of estrogen receptors on the malignant gallbladder tissue.

Sex steroids play an important part in the functioning of normal gallbladder, formation of gallstones and possibly in the pathogenesis of gallbladder cancer. Steroids receptors have been previously demonstrated on normal and malignant gall bladder tissues. To study this phenomenon further, we correlated clinicopathological features and survival with estrogen receptor (ER) status of the tumour in 30 patients with histologically-proven adenocarcinoma of the gallbladder. Estrogen receptor assay was performed immuno-histochemically utilizing Universal Immunoperoxidase Staining Kit. Tumor tissue was obtained either surgically or with fine needle aspiration of the gallbladder mass. There were 27 females and 3 males. Eighteen patients had estrogen receptors expressed on the malignant tissue, 12 were negative. Comparison of clinicopathological characteristics and survival between the two groups demonstrated no significant difference in gender, mean age, marital status and parity. Similarly, presence of gallstones, histologic grade or survival did not correlate with the estrogen receptor status. There is, however, a trend in favour of poorly differentiated tumors being more often receptor negative. Further studies are necessary to elucidate the biologic significance of these receptors.

A double-blind, placebo-controlled, randomized trial to evaluate the role of tetrachlorodecaoxide in the management of chemotherapy-induced oral mucositis.

We conducted a double-blind, placebo-controlled, randomized trial to evaluate the efficacy and safety of tetrachlorodecaoxide (TCDO) in patients with chemotherapy-induced mucositis. Sixty-two patients with World Health Organization grade II-IV oral mucositis were eligible for the study. They were randomized to receive TCDO or placebo, 10 ml, twice daily, swish and swallow, for 7 days. Patients were evaluated for oral pain, dysphagia, and oral intake. Downgrading and total duration of mucositis were documented. Thirty-two were randomized to receive TCDO. Thirty received the placebo. All were evaluable. Both arms were well matched for age, gender, type of underlying neoplasm, and prior history of oral mucositis. Intensity of initial symptoms, degree of mucositis, and time period between delivery of chemotherapy and development of mucositis were also similar. Post-therapy evaluation revealed no significant difference in the mean grade of oral and esophageal pain, or dysphagia between TCDO and placebo. Downgrading or total duration of mucositis did not differ between the two groups. Oral intake improved significantly in patients taking TCDO. Time to subjective improvement in oral pain was significantly shorter with TCDO (3.1 versus 3.6 days). Evaluation on day 3 revealed that 77% of those receiving TCDO were free of oral pain in comparison to 46% receiving placebo (P = 0.05). These results indicate that TCDO may be helpful in palliating some of the symptoms related to oral mucositis. The therapeutic benefit, however, is small and needs to be confirmed in a larger trial.

Efficacy of octreotide in diarrhoea due to Vibrio cholerae: a randomized, controlled trial.

Although octreotide, a long-acting analogue of somatostatin, is currently used in the treatment of chronic secretory diarrhoea due to various causes, its role in the management of acute secretory diarrhoea is not well established. In the present study, therefore, the therapeutic value of octreotide in the management of cholera, a classical example of acute secretory diarrhoea, was investigated. During an outbreak of cholera, patients admitted with acute secretory diarrhoea of < or = 24 h duration and a purging rate > 100 ml/h were enrolled on the study and randomly assigned to octreotide (N = 17) and control (N = 16) groups. All 33 patients received intravenous fluid replacement and antibiotic treatment (200 mg ofloxacin twice daily for 3 days, by mouth). Each patient in the octreotide group was also given a subcutaneous injection containing 100 micrograms octreotide every 8 h for a maximum of six doses. The stool output of each patient was recorded every hour until there had been none for an hour, which was taken as the endpoint. Mean (S.D.) total stool output was lower [6.56 (3.7) v. 9.7 (6.5) litres] and the mean (S.D.) duration of diarrhoea after admission was shorter [32.9 (15.6) v. 47.8 (22.3); P < 0.05] in the octreotide group than in the control group. However, as both groups generally had similar purging rates, the higher volume of stools from the control group was simply the result of the longer period of diarrhoea in this group. Octreotide therefore only decreased the duration of diarrhoea in the cholera patients.

Attitudes of Asian medical students towards smoking.

BACKGROUND: There have been numerous studies on smoking habits among young adults in developed countries. Similar data from developing countries are scanty. METHODS: A survey of medical students from one of the medical colleges in Pakistan assessed their smoking habits and attitudes towards smoking. In June 1993 a coded survey questionnaire was sent to each medical student at The Aga Khan Medical University in Karachi requesting data on their smoking habits, their attitudes towards smoking in various areas of the hospital, and their views about passive smoking and tobacco publicity. RESULTS: Of 324 medical students, 89% responded of whom 11% were current smokers. The incidence of smoking was greater among male students than females (17% versus 4%). The average age of initiation of smoking was 17 years and the major influence was friends. There was an increased awareness of harmful effects of smoking among medical students. Almost all felt that passive smoking was injurious to health. CONCLUSION: The prevalence of current smokers among Asian medical students was found to be 11%. Females smoked less than their male counterparts. There has been an increased awareness of the hazards of passive smoking among the medical students and most were in favour of legislative actions to discourage tobacco advertising.