Daniel Donato

Continent urinary diversion in gynecologic oncology

Pelvic exenteration is a salvage procedure used primarily for recurrent gynecologic carcinoma. Up to the present time, an ileal or colon conduit has been used for urinary diversion and the patient remains incontinent of urine. This is a preliminary report of nine patients with gynecologic carcinoma in whom a continent urinary diversion procedure was performed. A segment of distal ileum, the ascending colon, and part of the transverse colon are used to create the colonic reservoir. The segment of colon is opened along the tenia and folded onto itself. The walls of the ascending and transverse colon are anastomosed to detubularize this segment of bowel and eliminate the transient high pressure of the colon. Surgical staples are used for the anastomosis. The segment of ileum is tapered and three purse-string sutures (2-O silk) are placed at the level of the ileocecal valve to achieve continence. The short segment of ileum is then exteriorized as a stoma through which the patient catheterizes. Antirefluxing, non-tunneled ureterocolonic anastomoses are performed. The anterior wall of the reservoir is closed with absorbable staples. Postoperative urodynamic studies have shown maximum capacity of 750 ml and the area of continence to be at the ileocecal valve where the purse-string sutures are placed. All patients are continent and postoperative radiographs were negative for reflux. Follow-up was 6 to 12 months. The colonic reservoir is a capacious low-pressure system and warrants further clinical trials in patients with gynecologic cancer.

5-Year survival of patients with periaortic nodal metastases in clinical stage IB and IIA cervical carcinoma☆

From 1969 to 1981 thirty-six patients with stage IB and IIA cervical carcinoma were identified at pretherapy surgical staging laparotomy with histologically documented metastatic disease to the periaortic lymph nodes. All patients underwent a periaortic node dissection and all patients completed a course of extended-field radiotherapy in a postoperative setting. No major radio-therapeutic complications were encountered. The 5-year actuarial survival rate was 50%, with a median survival time of 29 months. The median time to recurrence was 10 months, while the median duration of survival following a recurrence was 7 months. Seventy-five percent of all recurrences occurred at distant sites. These data demonstrate that survival may be favorably influenced by employing extended-field radiotherapy in those patients with early-clinical-stage cervical cancer and periaortic nodal metastases. The subsequent development of distant metastases after such a treatment regimen emphasizes the need for adjuvant cytotoxic chemotherapy to enhance overall survival.

Surgical staging of gynecologic malignancies

The role of surgical staging in gynecologic malignancies has not been precisely defined at this time despite the conventional employment of this modality in the initial staging of ovarian neoplasms. Major discrepancies have been documented between clinical and surgical estimates of disease extent in cervical, endometrial, and vulvar carcinomas. We recently reviewed our experience with patients who were found to have positive periaortic nodes after surgical exploration for clinical Stage IB and Stage IIA cervical cancer. Postoperative extended field radiotherapy was employed with minimum complications and the 5‐year actuarial survival rate was 50% with a median survival time of 29 months. In order to justify the utilization of surgical staging for gynecologic neoplasms, it is necessary to demonstrate a survival advantage in patients where the precise extent of disease has been established and subsequent therapy tailored accordingly. In addition, it must be shown that surgical staging does not increase complications or decrease the efficacy of subsequent therapeutic interventions.

Ovarian carcinoma. Advances in diagnosis, staging, and treatment.

While major strides have occurred in the field of oncology and tumor biology, the basic problems of tumor heterogeneity, and mutational resistance to therapy continue to thwart progress in the diagnosis and treatment of patients with ovarian carcinoma. It is hoped ongoing clinical research using the above modalities will unfold ways to circumvent these and other major obstacles to the early diagnosis and treatment of patients with ovarian malignancies.

Cell Cycle Perturbations of Platinum Derivatives on Two Ovarian Cancer Cell Lines

Cisplatin continues to be one of the most commonly used cytotoxic agent. Problems of drug resistance and nephrotoxicity have generated interest in new platinum derivatives. In this study, we used flow cytometry to study their effects on cell kinetics and to see if the extent of cell cycle perturbations can be used to determine relative potency. The following four platinum derivatives were tested: cisplatin, carboplatin, 254S, and NK121 on two human ovarian cancer cell lines: BG1 and CAOV3. Flow cytometric analysis revealed a dynamic spectrum of cell kinetic perturbations, which included sequential S-G2 block, concomitant S-G2 block, and a dominant S block with abolition of G2 block. Platinum derivatives NK121, 254S, and CARBO induced an average of 54.5 +/- 5.6, 21.2 +/- 5.5, and 2.5 +/- 2.8% more S-G2 blocks than cisplatin, respectively. When comparing the severity of S-G2 blocks and requiring a p-value of 0.05, the order of increasing potency was: cisplatin, carboplatin, 254S, and NK121.

Chemical enhancement of cisplatin cytotoxicity in a human ovarian and cervical cancer cell line

While many advances have been made in the chemotherapy of gynecologic cancers, treatment failures remain a major clinical problem. A growing understanding of the mechanisms of tumor cell resistance to antineoplastic drugs provides a framework for the development of chemotherapy regimens containing agents capable of modulating tumor response. Using a short-term ATP bioluminescence assay we studied the ability of two methylxanthines (caffeine, pentoxifylline) and an inhibitor of ADP-ribosyl transferase (3-aminobenzamide) to enhance cisplatin cytotoxicity in gynecologic cancer cell lines. Our findings of significantly enhanced cisplatin-induced cytotoxicity with two different analysis techniques confirms the effectiveness of these agents. These results may have future clinical significance.

Synergistic effects of cis-platinum and cystosine arabinoside on ovarian carcinoma cell lines, demonstrated by dual-parameter flow cytometry

Ovarian cancer tends to remain confined to the peritoneal cavity even after widespread dissemination. In order to test the in vitro cytotoxic effect of cis-platinum (CP) and cytosine arabinoside (ara-C), a combination which, in theory, is particularly suitable for intraperitoneal (IP) administration, ovarian cancer cells were exposed to each drug alone and in combination and then sampled serially for 336 hr with cell counts and flow cytometry (FCM). We used dual parameter FCM analysis to study changes in DNA and nuclear protein simultaneously. There was good correlation between the degree of cell kill noted in the counts and the duration of observed cytokinetic disturbances in all the treated series. CP and ara-C alone produced temporary cytotoxic and cytokinetic changes. Together, the two agents produced an enhanced CP effect which lasted 336 hr and was accompanied by continued evidence of cell kill in the counts. We conclude that CP and ara-C in vitro act synergistically on ovarian cancer to achieve a high level of cell kill after a single simultaneous application.

Infectious complications after gastrointestinal surgery in patients with ovarian carcinoma and malignant ascites

One hundred four patients with ovarian cancer underwent intestinal reconstruction as part of a cytoreductive effort or for relief of intestinal obstruction from July 1980 to June 1990. Twenty-four percent of patients were obstructed preoperatively, while the remaining seventy-six percent had bowel resections performed in concert with a debulking procedure. The overall infectious complication rate was 14.4%. No statistical association was found between the presence of ascites at the time of laparotomy and infectious morbidity (P = 0.58). The use of a preoperative mechanical bowel preparation was associated with a significant reduction in infectious morbidity (P = 0.01). Additionally, patients considered in adequate nutritional condition experienced significantly less infectious complications than those patients in poor nutritional condition (P = 0.03). Intestinal procedures involving the large bowel were marginally associated with increased infectious complications (P = 0.13). Neither preoperative radiotherapy, the presence of preoperative obstruction, disease presence, extent of debulking, number of intestinal procedures, or hand versus stapled anastomosis was found to be significantly associated with infectious complications. It is concluded that the presence of ascites does not increase the infectious complication rate in ovarian cancer patients who undergo small or large bowel reconstructive procedures. Additionally, patients with preoperative bowel obstruction or previous abdominal radiation therapy were not found to experience a significant increase in the infectious complication rate in the current series.

In vitro evaluation of a novel chemotherapeutic agent, Adozelesin, in gynecologic-cancer cell lines

SummaryAdozelesin is a derivative of an extremely cytotoxic compound, CC1065. This entirely new class of drug binds preferentially to DNA and facilitates alkylation reaction. In the present study, we used the adenosine triphosphate (ATP) chemosensitivity assay to compare the cytotoxic potency of Adozelesin with that of common chemotherapeutic agents in ten gynecologic-cancer cell lines. Flow cytometry was also used to study its effects on cell-cycle kinetics. The mean drug concentrations required to produce a 50% reduction in ATP levels as compared with controls [IC50] were: Adriamycin, 0.17±0.06 μm; 4OH-Cytoxan, 18±3 μm; cisplatin, 17±7 μm; 5-fluorouracil, 183±116 μm; and Adozelesin, 11.0±5.4pm. Thus, Adozelesin was 104–107 times more potent than Adriamycin, cisplatin, 5-fluorouracil, and Cytoxan. Cell kinetics studies revealed significant S and G2 blocks such as those previously reported for other alkylating agents.

Ovarian adenocarcinoma complicated by malignant pericarditis

Neoplastic pericarditis is a rare complication of gynecologic malignancies. However, as illustrated in the case presented, the physician involved in the care of patients with cancer should be aware of this possible life-threatening complication. The case report is followed by a brief review of the pertinent clinical, pathophysiologic, and therapeutic aspects of this condition.