Unusual patterns of intermediate filament protein expression by the trophoblast and decidual cells of the short-tailed fruit bat, Carollia perspicillata.

In the short-tailed fruit bat (Carollia perspicillata) pregnancy can be prolonged by the occurrence of lengthy delays after implantation. This is associated with the development of highly invasive trophoblast that can penetrate the myometrium, mesenteries of the reproductive tract and the oviducts via perivascular (interstitial) routes. In order to confirm the identity and distribution of this trophoblast, intermediate filament protein immunocytochemistry was utilized. In some respects the expression of these proteins differed from what has been reported for more commonly-studied species. Cytotrophoblast in the placenta, its cytotrophoblastic shell and the highly invasive trophoblast strongly expressed cytokeratins. As pregnancy progressed, however, cytokeratin expression by syncytiotrophoblast lining much of the placental labyrinth became very weak. The cytotrophoblastic shell and highly invasive trophoblast also expressed vimentin. The highly invasive trophoblast was unusual in that it developed dendritic processes that sometimes extended out into adjacent tissues in great profusion. Decidual cells generally expressed desmin and vimentin; however, some also coexpressed cytokeratins. These observations indicate that some of the trophoblast in Carollia undergoes a significant epithelial-mesenchymal transformation. They also suggest that caution should be exercised in relying upon intermediate filament proteins as markers for cell identification purposes in exotic species, or when the patterns of protein expression by fetal and maternal cells might be altered in pathological or experimental situations.

Quantitative methodologies for selection of patients with recurrent abdominopelvic sarcoma for treatment.

Peritoneal sarcomatosis is a major cause of surgical treatment failure in patients with abdominal or pelvic sarcoma. In the past, patients with this condition have had a lethal outcome. In this study, 43 consecutive patients with recurrent sarcomatosis were studied in order to evaluate an aggressive reoperative approach. In all patients, the goal of surgery was to resect all recurrent sarcoma in the abdomen and pelvis. In 30 patients in whom sarcomatosis was demonstrated and in whom a complete cytoreduction could be performed, resection was associated with peri-operative intraperitoneal chemotherapy with doxorubicin or cisplatin plus doxorubicin. Using a standardised and quantitative methodology to assess local-regional recurrence and dissemination on peritoneal surfaces, the clinical features that may affect prognosis were tabulated and analysed statistically. The median survival of these 43 patients was 20 months. Clinical features that had a significant impact on survival were involvement of less than six abdominopelvic regions (P = 0.0009), an increase in the involvement of abdominopelvic regions of less than four regions (P = 0.0007), involvement of less than 10 anatomic sites (P = 0.0002), complete cytoreduction with tumour reduced to nodules < 2.5 mm (P = 0.005) and a Peritoneal Cancer Index less than 13 (P = 0.01). Histological type and grade of recurrent sarcoma were not correlated with prognosis. In the multivariate analysis, an increase in abdominopelvic regions by four or more showed a risk ratio of 18.5. The involvement of 10 or more anatomic sites showed a risk ratio of 5.9. These data suggest that selected patients with recurrent sarcoma should be considered for further treatment and that the results of aggressive reoperative surgery and peri-operative intraperitoneal chemotherapy are greatly dependent on the volume and distribution of disease, determined at the initiation of therapy. Because of the great likelihood of local-regional treatment failure, the use of peri-operative intraperitoneal chemotherapy in a randomised study in patients with primary abdominopelvic sarcoma should be considered.

Pathobiology of peritoneal carcinomatosis from ovarian malignancy.

A detailed analysis of the patterns of treatment failure of ovarian malignancy may lead to a more comprehensive understanding of the natural history of the disease. A hypothesis was generated that suggests treatment failure was caused by ovarian cancer persistence and by reimplantation of tumor emboli trapped within surgically traumatized tissues. Nine ovarian cancer patients who had previously undergone standard surgical removal of the primary cancer were prospectively studied at a reoperative procedure. The operative findings at the time of primary cancer surgery and reoperative surgery were scored for the presence of tumor in 9 abdominopelvic regions and 17 abdominopelvic sites. These data were then statistically analyzed. In 7 of the 9 patients ovarian cancer recurrence was associated with an increased intraperitoneal dissemination of tumor. A mean of 3.1 regions were involved at the time of the initial surgery and 5.3 were involved at reoperation. The regions most consistently involved were those in close proximity to the primary cancer. The anatomic sites that showed a preponderance of recurrence were the rectosigmoid colon, cul-de-sac of Douglas, left paracolic gutter, vagina, and abdominal incision. Traumatized sites always showed more cancer recurrence than nontraumatized sites. The vaginal cuff and abdominal incision, sites free of cancer after hysterectomy but at high risk for tumor cell entrapment, were disproportionately common sites for cancer found at reoperation. This study shows that in this reoperative setting ovarian cancer recurrence is most common in the pelvis and the left lower part of the abdomen. The cul-de-sac of Douglas and the rectosigmoid colon are anatomic sites at extreme risk for disease progression. These are sites in which ovarian cancer implants not removed by routine hysterectomy and bilateral salpingo-oophorectomy will persist. Also, sites traumatized by surgery were disproportionately involved by cancer at reoperation. These data may be interpreted to suggest that anatomic sites with cancer persistence and with cancer implantation induced by surgical trauma are the most common sites for ovarian cancer recurrence in this select group of patients.

Patterns of spread of recurrent intraabdominal sarcoma.

A prominent site for recurrence of retroperitoneal and visceral sarcoma is the abdominal cavity. In an attempt to understand the causation of local and regional recurrence, 21 sarcoma patients who had previously undergone "complete" surgical removal of the primary tumor were prospectively studied. Data were obtained retrospectively from the first operation and prospectively from the reoperative procedure at the Washington Cancer Institute. At the primary and reoperative surgeries, 9 abdominopelvic regions and 21 sites were scored and then cataloged in a standardized fashion. Tumor locations and surgical resections were statistically analyzed in an attempt to establish patterns of recurrence within the abdomen and pelvis. There was a significant difference in sites of recurrence when sarcomas that involved the parietal structures were compared with those that involved small bowel. Peritoneal implants (nodular recurrences) were uniformly present in both groups. In contrast, resection site recurrences were very common with primary sarcomas invested by parietal peritoneum, while they were absent in those covered by visceral peritoneum. When primary surgeries were compared with reoperations, there was an increasing intraabdominal dissemination; the mean number of regions increased from 1.81 to 5.13. The change in distribution of sarcoma deposits at reoperation was greatest in right upper (because of liver surface) central and pelvic abdominopelvic regions and lowest in the left upper and epigastrium. The four anatomic sites that revealed a significant increase in involvement at the time of recurrence were the greater omentum, liver surface, large bowel, and the cul-de-sac of Douglas (all p < 0.002). Regions with tumor involvement or regions subjected to surgical trauma at the time of primary sarcoma resection were significantly more likely to show sarcoma deposits than to be sarcoma free at reoperation. These data taken together may suggest that sarcoma tumor emboli are frequently present in the abdomen at the time of resection of the primary cancer and that these tumor emboli are entrapped in fibrinous material at or immediately adjacent to sites of surgical trauma and along narrow margins of resection. Tumor cell entrapment of sarcoma emboli released into the peritoneal cavity prior to or at the time of sarcoma resection may help explain the distribution of nodular and fusiform recurrence of abdominopelvic sarcoma.

Pharmacokinetic studies of intraaortic stop-flow infusion with 14C-labeled mitomycin C.

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 microCi 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.

Intraaortic stop-flow infusion: pharmacokinetic feasibility study of regional chemotherapy for unresectable gastrointestinal cancers.

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 of 14C-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.