The feasibility of early administration of combination chemotherapy following cytoreductive surgery and second-look operation in patients with stage III ovarian carcinoma: a pilot study.

The purpose of this study is to evaluate the feasibility of early use of modified PAC-1 chemotherapy following debulking surgery and its efficacy by assessing disease status during a second-look operation. Twenty-six consecutive previously untreated patients with stage III ovarian carcinoma were evaluated in a prospective study over the 5-year period March 1981 to August 1986. Initial exploratory laparotomy was performed for staging and maximum cytoreduction. Within 24 hr postoperative modified PAC-1 (M-PAC-1) combination chemotherapy was administered and then repeated every 4 weeks for 11 months which was then followed by second-look operation. Patients were analyzed according to the following pretreatment characteristics: age, FIGO stage, histologic tumor type, extent of initial surgery, size of residual tumor, and findings during second-look. Nineteen patients were evaluable. No evidence of either microscopic or macroscopic disease was noted in 15 patients (79%), whereas the remaining 4 (21%) exhibited persistent disease. Of the remaining 7 patients not undergoing SLO, 4 completed 12 courses of chemotherapy but did not undergo surgery for medical reason (n = 2) or patient refusal (n = 2). Two more patients refused chemotherapy after 9 courses and the seventh patient expired with persistent disease after 8 courses. The early use of combination chemotherapy was well tolerated. Neurological, hematological, and renal toxicity was never severe enough to cause discontinuation of therapy.

Alteration of chemotherapy toxicity using a chemically defined liquid diet in rats.

Controversy exists as to whether administration of a chemically defined diet alters toxicity to chemotherapy. The purpose of this study was to evaluate toxicity to methotrexate in rats fed a chemically defined liquid diet or a regular chow diet. In the first study, 48 adult rats were randomized to be fed a chemically defined liquid diet or a regular diet for 14 days when methotrexate (25 or 50 mg/kg) was given. All liquid diet rats became anorexic and died within 96 h, while no deaths were observed in rats fed regular diet. When 20 liquid diet and regular diet rats were pair-fed to equalize caloric intake before and after methotrexate administration, similar mortality results occurred. In a second study, methotrexate (50 mg/kg) or saline was given and 60 h later all animals were sacrificed to obtain small bowel luminal cultures and tissue sections for histological evaluation. Administration of the liquid diet altered small bowel flora to predominantly Escherichia coli and Pseudomonas sp. and histology showed severe small bowel mucosal enteritis in comparison with regular diet rats. To evaluate whether the changes in intestinal flora or alterations in drug pharmacokinetics were responsible for the increased mortality, two additional studies were done. Gentamicin (4.8 mg/kg/day) was given p.o. or i.m. to the rats on the chemically defined liquid diet. A significant reduction of intraluminal bacteria occurred, but survival time was not improved in animals receiving antibiotics. When mean serum methotrexate levels were analyzed in non-antibiotic-treated rats, drug concentrations were significantly increased at 24, 36, and 48 h after methotrexate injection in the elemental liquid diet rats compared with chow diet rats. Administration of a chemically defined liquid diet to rats receiving methotrexate increased the occurrence and severity of intestinal enteritis, altered intraluminal bowel flora, and decreased clearance of methotrexate from the serum.

Value of splenectomy in non-Hodgkin's lymphoma.

A retrospective review of patients with non-Hodgkin's lymphoma (NHL) who underwent palliative splenectomy for splenomegaly, hypersplenism, or autoimmune complications was done. From 1970 through 1981, 46 patients had palliative splenectomy for splenomegaly alone (n = 3) or various hematologic abnormalities with (n = 35) or without (n = 8) splenomegaly. Splenectomy was performed for life-threatening (n = 7), severe (n = 15), or mild (n = 24) symptoms/signs. The most common hematologic abnormalities were thrombocytopenia (platelet count less than 120,000/mm3; n = 38) and/or anemia (hemoglobin level less than 11.0 g/mm3; n = 29). Response to splenectomy was defined as greater than a threefold increase in preoperative platelet count and/or an increase in hemoglobin levels to greater than 11.0 g/mm3 in the first postoperative month. Four patients with thrombocytopenia did not respond, whereas 33 patients responded with greater than a sevenfold increase in platelet count. All four nonresponders died of complications of thrombocytopenia or progressive disease. Eighteen of 28 (64%) patients with anemia responded to splenectomy. Larger spleens (2000 g versus 1410 g; P less than 0.05) and lower platelet counts (42,000 versus 75,000; P less than 0.05) were found in all nonresponding patients. Responders and nonresponders could not be distinguished on the basis of age, sex, race, duration of disease or splenic involvement, primary site of disease, histopathologic findings, bone marrow or lymphangiogram results, or prior chemotherapy and radiotherapy. Patients with mild symptoms/signs were more likely to respond hematologically than patients with life-threatening or severe symptoms/signs (86% versus 54%; P = 0.06). For all patients, 2- and 5-year survival from the time of splenectomy was 44% and 26%, respectively. Median survival was 18 months (range, 1-144 months). Inability to reverse hematologic abnormalities was associated with poor survival. All nonresponding patients died within 36 months of surgery, whereas 5-year survival in responding patients was 40%. Nine of 30 patients (30%) who responded hematologically survived longer than 5 years, but this group of patients could not be distinguished from the remaining patients on the basis of age, sex, race, duration of disease or splenic involvement, primary site of disease, histopathologic features, bone marrow or lymphangiogram results, or prior chemotherapy and radiotherapy. Surgery was well-tolerated (mortality, 9%; morbidity, 21%). All surgical mortalities and 78% of complications occurred in patients operated on for life-threatening or severe symptoms/signs.(ABSTRACT TRUNCATED AT 400 WORDS)

Effects of postoperative infusion of branched chain amino acids on nitrogen balance and forearm muscle substrate flux.

A branched chain amino acid (45% BCAA)--enriched solution was compared with a standard amino acid (25% BCAA) solution in a randomized blinded study in eight patients undergoing cystectomy and ileal loop diversion. Solution administration rates were designed to provide 20 kcal/kg/day and 0.26 gm nitrogen/kg/day postoperatively from days 1 to 8. Daily urine creatinine and nitrogen levels were measured. On day 4 during infusion, forearm blood flow was measured by capacitance plethysmography. Arterial and antecubital deep venous blood samples were drawn simultaneously for determinations of glucose, lactate, pyruvate, and amino acids; substrate flux was calculated (mumol/ml/min, uptake = +, release = -). The mean total amino acid flux was significantly improved In the 45% BCAA group (+1.7 +/- 0.4) versus the 25% BCAA group (-0.03 +/- 0.2, P less than 0.05). The mean total BCAA flux was significantly improved in the 45% BCAA group (+1.1 +/- 0.4) compared with the 25% BCAA group (-0.03 +/- 0.2) (P less than 0.02). There were no significant differences between groups in alanine, glutamine, glucose, lactate, or pyruvate forearm flux. The cumulative adjusted 7-day nitrogen balance was -1.4 +/- 7 gm in the 45% BCAA group and -14.2 +/- 4 gm in the 25% BCAA group (NS). the 45% BCAA solution resulted in significant uptake of total amino acid and BCAA into forearm muscle, which was not significantly demonstrated in whole body nitrogen balance studies. Sixty-six percent of the increase in total amino acid forearm flux with use of the 45% BCAA solution was due to the uptake of BCAA even though less leucine was given compared with the 25% BCAA solution.