Browsing by Author "Samel, S."

The purpose of this study was to assess the extent of the systemic absorption of cisplatin during intraoperative hyperthermic peritoneal lavage (IHPL) in patients with locally advanced gastric cancer. Materials and Methods: The pharmacokinetics and nephrotoxicity of cisplatin were analyzed in patients receiving IHPL (8000 ml of Ringer's solution containing 150 mg/m(2) cisplatin and 15 mg/m(2) mitomycin C for one hour at 43.5 degreesC). Levels of ultrafiltrable platin were determined by flameless atomic absorption spectrometry. Nephrotoxicity was assessed by nephelometric analyses of urinary marker-proteins. The data were compared to respective analyses in patients receiving intravenous cisplatin. Results: Twenty-four patients received five applications of cisplatin as IHPL (five patients) and 53 applications of intravenous cisplatin (21 patients). Platin levels within the lavage fluid declined monophasically (half-life, 0.48+/- 10 hours; area under curve (AUC) 29274+/-9075 ng/ml h). The pharmacokinetic parameters calculated for IHPL vs. intravenous application of cisplatin were: maximum plasma levels 2392 407 vs. 1349 692 ng/ml; terminal half-lives 93+/-73 vs. 36+/-9 hours; AUC 9508+/-856 vs. 11627+/-3372 ng/ml h; total urinary excretion of platinum 24+/-6 vs. 49+/-13% of dose, renal clearance 127+/-34 vs. 145+/-35 ml/min. Pathologic urinary albumin excretion occured on days 9+/-0 vs. 5+/-2 (maximum 232+/-179 vs. 20+/-20 mg/l). Plasma creatinine levels rose to 1.5+/-0.4 vs. 0.9+/-0.1 mg/dl on days 15 4 vs. 16 26 The degree of albuminuria was related to the clearance of platin from the lavage fluid (p=0.048). Conclusion: A significant amount of intraperitoneally applied cisplatin is available systemically and probably adds to the nephrotoxicity of IHPL.

The prognosis of peritoneal spread from gastrointestinal cancer and subsequent malignant ascites is poor, and current medical treatments available are mostly ineffective. Targeted chemotherapy with intraperitoneal prodrug activation may be a beneficial new approach. L293 cells were genetically modified to express the cytochrome P450 enzyme 2B1 under the control of a cytomegalovirus immediate early promoter. This CYP2B1 enzyme converts ifosfamide to its active cytotoxic compounds. The cells are encapsulated in a cellulose sulfate formulation (Capcell(TM)). Adult Balb/c mice were inoculated intraperitoneally with 1 x 10(6) colon 26 cancer cells, previously transfected with GFP to emit a stable green fluorescence, by injection into the left lower abdominal quadrant. Two or five day's later animals were randomly subjected to either i.p. treatment with ifosfamide alone or ifosfamide combined with microencapsulated CYP2B1-expressing cells. Peritoneal tumor volume and tumor viability were assessed 10 days after tumor inoculation by means of fluorescence microscopy, spectroscopy and histology. Early i.p. treatment with ifosfamide and CYP2B1 cells resulted in a complete response. Treatment starting on day 5 and single-drug treatment with ifosfamide resulted in a partial response. These results suggest that targeted i.p. chemotherapy using a combination of a prodrug and its converting enzyme may be a successful treatment strategy for peritoneal spread from colorectal cancer.

Background: Intraoperative hyperthermic peritoneal chemotherapy (IHPC) after total gastrectomy for advanced, serosa-penetrating gastric cancer has been demonstrated in several studies to reduce the incidence of peritoneal carcinosis and to prolong survival, Methods: In a prospective pilot study, nine patients with advanced gastric cancer were selected to receive II-IPC with Mitomycin and Cisplatin after total gastrectomy and systematic lymphadenectomy. Results: All patients had nodal, and four patients distant. metastases. Six patients (66%) suffered from post-operative complications including renal failure, pancreatitis. pancreatic fistula and anastomotic dehiscence. Thirty-day mortality was zero. Six patients died within 3-10 months after surgery, Five of these deaths were related to peritoneal carcinosis and one patient died from cardiac failure 3 months after surgery. Three patients. respectively, have been alive for 12, 70 and 24 months at present, with suspected peritoneal tumour in the last patient, Thc l-year probability of survival among our patients receiving IHPC is 29%. Conclusion: Intraoperative hyperthermic peritoneal chemotherapy carries a high risk of peri-operative complications and was nor able to prevent or delay peritoneal tumour recurrence in patients with advanced gastric cancer.

The rare neoplastic cystic adenomas of the pancreas form two groups of tumors: macrocystic mucinous and microcystic serous adenomas. Both entities show specific radiologic and histologic features. Several recent case reports, however, suggest some diversity within the group of microcystic serous adenomas. We present the case of a young man operated because of epigastric pain for 12 months and a palpable microcystic tumor of the pancreatic head. Multiple cysts communicating with branches of the pancreatic duct in an alveolar-like pattern were demonstrated on endoscopic retrograde cholangiopancreatography. Histologic examination of the specimen confirmed the diagnosis of a serous adenoma of the pancreas. The tumor morphology in this case may suggest a ductal origin of microcystic serous adenomas.