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Background and Objectives: The growth and progression of ovarian tumor metastases at the peritoneal surfaces of the abdominal cavity are coupled with neovascularization. Newly formed tumor vessels show a more diffuse pattern and are more permeable for macromolecules than normal vessels. We investigated the possibility to detect (small) ovarian metastases in the abdominal cavity by means of fluorescein angiography., Study Design/patients and Methods: Eighteen patients known with ovarian cancer or with suspicion for this disease received sodium fluorescein intravenously in different doses (0.4-1.6 ml of a 25% solution), whereafter fluorescence detection by laparoscope was carried out. The distribution pattern of fluorescein was gained from 0 to 120 min by pooling the data collected in different patients at various time intervals., Results: Three phases could be discriminated, that is, rapid filling of blood vessels after administration of fluorescein, diffuse extravasation of fluorescein into surrounding tissues, and clearance of fluorescein from vessels and surrounding tissue. Differences in accumulation of fluorescein could be visualized only after 1 hour or more. Fluorescence imaging more then 60 minutes after administration of fluorescein did not give additional information compared to the inspection using white light, which was confirmed by histology. These observations were dose-independent., Conclusions: The concentration gradient differences of fluorescein between healthy and pathological tissue in the abdominal cavity are too small to indicate tumor neovascularization., ((c) 2004 Wiley-Liss, Inc.)

Background: HIPEC is a new treatment modality for abdominal cancers that combines cytoreductive surgery with Hyperthermic, Intraoperative Peritoneal Chemotherapy, followed by systemic chemotherapy. A significant survival benefit has been shown for HIPEC compared with systemic therapy alone. However, it is not clear what is the contribution of i.p. drug delivery and what influence the mild hyperthermia has on the uptake of cisplatin in abdominal tumors., Materials and Methods: We used a peritoneal perfusion system in rats to compare the pharmacokinetics and pharmacodynamics of cisplatin, after normothermic (37 degrees C/90 minutes) and hyperthermic (40 degrees C/90 minutes) intra-peritoneal perfusion, with an i.p. bolus injection., Results: Hyperthermic perfusion with 15 micrograms/ml (in 200 ml) cisplatin gave equivalent plasma drug levels to a maximum tolerated dose (MTD) i.p. bolus injection of 4 mg/kg (36 micrograms/ml in 20 ml). The drug concentration in small (1-5 mm) intra-peritoneal tumors was also comparable for both these treatments, and for normothermic perfusion., Conclusion: Mild hyperthermic perfusion with cisplatin (40 degrees C/90 minutes) did not improve drug uptake in small intra-peritoneal tumors, relative to normothermic perfusion or i.p. bolus injection.

In 75% of cases, ovarian carcinoma has already metastasized in the abdominal cavity at the time of diagnosis. For determination of the necessity for a supplementary therapy, in addition to surgical resection, it is important to localize and stage microscopical intraperitoneal metastases of the tumor. Intraperitoneal photodetection of tumor metastases is based on preferential tumor distribution of a fluorescent tumor marker. The time-dependent differences in drug concentration between tumor and normal (T/N) tissues can be used to visualize small tumors. We performed fluorescence measurements on abdominal organs and tumor in the peritoneal cavity of rats. 5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) was used as the fluorescent marker. Three different drug doses (100, 25 and 5 mg/kg) were used and PpIX fluorescence profiles were followed up to 24 h after intravenous administration. Maximum T/N ratios were found 2-3 h after administration of ALA with all drug doses. A significant T/N tissue contrast was obtained for all abdominal organs tested after administration of 5 mg/kg.

Objective: To apply (HIPEC) using mitomycin in patients with peritoneal carcinomatosis., Design: Descriptive., Method: The HIPEC treatment includes cytoreductive surgery and subsequent peritoneal lavage with exposure of the superficial tumour residues to a high concentration of a cytostatic drug at an intra-abdominal temperature of 40-42 degrees C. The HIPEC treatment was given to 24 patients with pseudomyxoma peritonei and to 29 patients with peritoneal carcinomatosis of colorectal origin. The adequate dose of mitomycin was determined in the Netherlands Cancer Institute in 26 patients: doses of 15 mg/m2 (n = 8), 25 mg/m2 (n = 3), 35 mg/m2 (n = 7) and 40 mg/m2 (n = 8) were administered., Results: The maximal tolerable dose of mitomycin appeared to be 35 mg/m2, while unacceptable toxicity was recorded at a dose of 40 mg/m2. Therefore 35 mg/m2 was used in subsequent cases. Among the patients with pseudomyxoma peritonei 8 developed severe complications, two of which were fatal. After a median follow-up of 12 months, 21 patients were alive of whom 18 were free of disease. Among the patients with peritoneal carcinomatosis of colorectal origin one patient died from a treatment-related complication. After a median follow-up of 18 months, 18 patients were alive of whom 11 were free of disease. The actuarial 2 year survival was 59%., Conclusion: In the Netherlands Cancer Institute HIPEC treatment is considered the treatment of choice for pseudomyxoma peritonei. The results in cases of peritoneal carcinomatosis of colorectal origin are promising, but the results of a randomized trial are awaited.