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Abstract: Background: This study attempted to increase the exposure of gastrointestinal tract tissues to chemotherapy by prolonging the first pass of intraaortically administered drug by temporary occlusion of vascular structures. Methods: Bolus infusion of14C-labeled mitomycin C (MMC) mixed with unlabeled MMC was performed in dogs. Distribution of MMC in gastrointestinal tract tissues was studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted the control group. Vascular flow was controlled in four ways for 30 min: type I—stop-flow infusion (SFI) with clamping of the abdominal aorta above the celiac and below inferior mesenteric artery; type II—with additional clamping of the inferior vena cava above the diaphragm; type III with additional clamping of the portal vein in the hepatoduodenal ligament; and type IV—with surgical exclusion of nongastrointestinal branches of the aorta in addition to type II clamping. Results: Type II and IV produced a 3–10-fold increase in exposure to MMC of major gastrointestinal tissues as compared with intravenous infusion. Area under the curve ratios with type IV were most prominent in the following tissues: stomach, pancreas, liver, and mesenteric lymph node. Conclusion: Access of MMC to several gastrointestinal tissues was increased through SFI. Type IV infusion was the most effective. Tissue exposure to MMC was especially advantageous for stomach, pancreas, liver, and mesenteric lymph node.

PURPOSE: Use of laparoscopic techniques for resection of colon and rectal cancer has raised considerable controversy. There is increasing concern that wound recurrence and peritoneal dissemination may represent a potentially fatal complication of this technique. METHODS: The surgical literature was reviewed, and clinical course of two patients is presented. RESULTS: Our two patients had tumor recurrence in the laparoscopy port sites within one year after laparoscopic-assisted colectomy for Dukes B adenocarcinoma of the colon. At laparotomy, diffuse peritoneal carcinomatosis without lymph node or liver metastases were found in both patients. They were treated by surgical resection of recurrent disease combined with heated intraoperative intraperitoneal mitomycin C chemotherapy and five days of early postoperative intraperitoneal 5-fluorouracil. These patients are clinically free of disease at 1.5 years after treatment of peritoneal implants. CONCLUSIONS: Cancer recurrence in abdominal wall incisions after laparoscopic colectomy has been reported in an increasing number of patients. It is possible that this technique should be abandoned. Cytoreductive surgery combined with intraperitoneal chemotherapy may represent the most adequate treatment of recurrent cancer that occurs following laparoscopic colectomy.

This pharmacokinetic study attempted to improve the exposure of gastrointestinal tract tissues to chemotherapy by increasing the transit time of a first pass of a drug through the vascular system. Bolus infusion of 9 mg mitomycin (MMC) mixed with 1 mg of MMC labeled by 50 μCi of 14C was performed in 18 mongrel dogs. Pharmacokinetics of MMC in peripheral, portal, and aortic blood were studied under different types of major vessel occlusion. Three dogs with intravenous infusion constituted a control group. In 15 dogs MMC was infused intraaortically with the catheter's tip at the level of the celiac and superior mesenteric artery. Vascular flow was controlled in four different ways for 30 min: Type I-Type IV. In Type IV the abdominal aorta and vena cava inferior were occluded after surgical exclusion of all nongastrointestinal branches of aorta. Blood samples were obtained during a 90-min period. After solubilizing the samples, 14C-labeled MMC activity was counted by a scintillation counter. For stop-flow infusion Type I, II, III, and IV, area under the curve (AUC) ratios for portal blood versus systemic circulation were 1.6:1, 2.9:1, 2.9:1, and 8.8:1, respectively (statistically significant for Types II, III, and IV). The highest value of AUC, peak MMC concentration, and lowest clearance in portal blood were achieved in SFI Type IV. Exposure to MMC was the greatest with SFI Type IV, making this type of aortic stop-flow infusion the most favorable mode of drug administration from a pharmacokinetic perspective.