Kelly L. Molpus

Characterization of a xenograft model of human ovarian carcinoma which produces intraperitoneal carcinomatosis and metastases in mice.

A new xenograft model for human epithelial ovarian carcinoma with extensive intraperitoneal (i.p.) carcinomatosis as the predominant disease manifestation, is described. Cells from the established NIH:OVCAR‐5 cell line were injected i.p. into 6‐to 8‐week‐old Swiss nude mice. Comparative analyses between cells cultured in vitro and tumor cells derived ex vivo were performed to assess histologic features, immunohistochemical cell markers, hormonal receptor expression, adhesion to extracellular matrix molecules and chromosomal constitution. Macroscopically, the extent of tumor development appeared to be site‐dependent and tumor cell survival was dose‐dependent. Advanced disease was characterized by extensive solid tumor burden and ascites with parenchymal invasion, lymphatic metastases and vascular dissemination. Individual tumor nodules exhibited developing neovasculature characterized by the absence of mature basement membrane. Despite some histologic loss of cellular differentiation in advanced disease, antigenic expression was preserved, distinguishing these cells as epithelial in origin. Karyotyping of tumor cells demonstrated multiple numeric and structural chromosomal abnormalities. Serum and ascites CA 125 levels were consistently elevated only in tumor‐bearing mice. This new murine model closely resembles the aggressive disease process of human epithelial ovarian carcinoma, in which the efficacy of i.p. and systemic therapeutic modalities can be investigated.

Light Dosimetry for Intraperitoneal Photodynamic Therapy in a Murine Xenograft Model of Human Epithelial Ovarian Carcinoma

Few studies have been published to date measuring spatially resolved fluence rates in complex tissue geometries. Here the light distributions of three different intraperitoneal light delivery geometries in a murine ovarian cancer model were investigated to assess their influence on the tumorcidal efficacy of photodynamic therapy (PDT). In vivo fluence rate measurements in the peritoneal cavities of mice, with the light intensity being mapped in three transverse planes, were performed using fiber‐optic detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to a PDT protocol comprising three separate treatments administered at 72 h intervals, each consisting of a 0.25 mg kg intraperitoneal injection of benzopor‐phyrin derivative‐mono acid ring A followed 90 min later by delivery of 15 J of 690 nm light, was measured. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass. Fluence rate measurements showed large variations in the fluence rate distribution for similar intended treatments. The most uniform and reproducible illumination was achieved using two 18 mm long cylindrical emitting optical fibers. The biological response was comparable to that produced when a flat‐cleaved end optical fiber is used to illuminate the four quadrants of the abdomen sequentially. While a good reproducibility in tumor induction in this animal model exists, no correlation was found between the fluence rate distribution measured in one group of animals and the biological response in a separate group of similarly treated animals. Due to the large intra‐animal variability in fluence rate distribution, representative fluence rate mapping in complex tissue geometries is of limited value when applied to an individual PDT treatment. Thus, surveillance of the fluence rate during individual treatments will be required for acceptable PDT dosimetry. To improve the versatility of this particular animal model for PDT research, a large number of extended sources are required to increase uniformity of the illumination in order to reduce unwanted cytotoxic side effects resulting from foci of high fluence rates. In this way, subsequent increase of the total energy delivered to the tumor may be possible.

Advanced ovarian carcinoma diagnosed during pregnancy in a patient with human immunodeficiency virus infection

primary reconstruction has failed. Reported are the results of successful pregnancies in four young adult females. who had previously undergone a flap vaginoplasty as part of earlier management and more recently a continent right colonic urinary reservoir with a perineal stoma (Indiana pouch). Pregnancy in each of these patients was characterized by several urinary tract infections, cervical prolapse and mild to severe maternal hydronephrosis. All of the patients had some degree of difficulty with clean intermittent catheterization. One patient required an indwelling catheter with prolonged bed rest. Maternal hydronephrosis resolved after delivery in all instances. All four patients delivered their infants by way of cesarean section, either emergently for maternal or fetal distress or electively. Cervical prolapse did not resolve in three patients and will require surgical repair. After delivery, all patients returned to their previous pattern of clean intermittent catheterization without loss of continence. All the infants delivered were healthy with appropriate weights and high Apgar scores (more than 8). Orthotopic (perineal stoma) continent urinary diversion is not a contraindication to pregnancy. However, our experience mandates delivery by cesarean section with close monitoring for maternal or fetal distress during gestation.