Indwelling ureteral catheters are commonly used to splint injured ureters or to relieve obstruction. This study evaluated the possibility of using ultrasound guidance in the removal of internal ureteral catheters in women. During the 12-month period from August 1990 to August 1991, patients who desired the removal of indwelling ureteral catheters were sent to the outpatient ultrasound division instead of the urology clinic. They were instructed to come with a full bladder, or a saline infusion was required. Abdominal or vaginal ultrasound was first performed to locate the ureteral catheter. Blunt-tipped alligator forceps were used to remove the catheters under direct, real-time ultrasound guidance. A total of six catheters was removed from five patients. The average removal time was 12 +/- 4 (SD) minutes, with good patient acceptance. Further studies are required to establish the safety and efficacy of the procedure.

Adult↗

PubMed1993

National survey of ovarian carcinoma. Part V. The impact of physician's specialty on patients' survival.

BACKGROUND: Data analysis of the recent National Survey of Ovarian Carcinoma revealed significant differences in patterns of care among various physician specialists. The goal of this study was to determine if different care patterns led to differences in patient survival. METHODS: Data were collected from 25 consecutive patients with ovarian cancer diagnosed in 1983 and 1988 from 1230 hospitals with cancer programs across the United States. RESULTS: A total of 12,316 patients from 904 hospitals were registered, of whom 20.8% were cared for by gynecologic oncologists (GYO), 45.0% by obstetrician-gynecologists (OBG), and 21.1% by general surgeons (GS). GYO preferred the upper-lower midline incision in 44.1% of patients, whereas both OBG and GS chose the low midline approach in 44-45%. GYO performed more hysterectomies, oophorectomies, omentectomies, and lymph node and peritoneal biopsies than did other specialists. Although the rates of surgery of the small intestine were comparable between GYO and GS, the latter performed significantly more colostomies and resections of the large intestine. The optimal debulking rates were: GYO, 42-45%; OBG, 40-44%; and GS 25%. There was no significant survival difference between patients cared for by GYO and those cared for by OBG for all stage divisions. However, with the exception of patients with Stage I disease, patients cared for by GS had significantly reduced survival than did those cared for by GYO and OBG (P < 0.004). CONCLUSION: Efforts must be made to ensure that more patients with ovarian cancer are cared for by physicians in the appropriate specialties.

Female↗

PubMed1993

National survey of ovarian carcinoma. VI. Critical assessment of current International Federation of Gynecology and Obstetrics staging system.

BACKGROUND: The Commission on Cancer of the American College of Surgeons recently completed a national survey of patients with ovarian cancer. From the large database, the prognostic value of current International Federation of Gynecology and Obstetrics (FIGO) staging system for ovarian carcinoma was re-examined. METHODS: Data was collected from 25 consecutive ovarian carcinomas diagnosed in 1983 and 1988 at 904 hospitals with cancer programs. Among a total of 12,316 cases, 5156 patients had long-term survival data. RESULTS: The overall 5-year survivals were 88.9 +/- 0.9%; 57.1 +/- 2.4%; 23.8 +/- 1.3%; and 11.6 +/- 0.9% for Stages I, II, III, and IV, respectively. Pairwise survival comparisons using Lee-Desu statistic confirmed the prognostic value of current staging system (P < 0.00001). When survival data was substratified further to substage division, the 5-year survivals were: IA, 92.1 +/- 0.9%; IB, 84.9 +/- 3.4%; IC, 82.4 +/- 2.0%; IIA, 69.0 +/- 4.3%; IIB, 56.4 +/- 3.6%; IIC, 51.4 +/- 4.5%; IIIA, 39.3 +/- 2.8%; IIIB, 25.5 +/- 2.6%; IIIC, 17.1 +/- 1.4%; and IV, 11.6 +/- 0.9%. As the disease process becomes more advanced, patients' survival reduces proportionally. However, the survival reduction is relatively small between IB-IC and IIB-IIC divisions. Survival comparisons revealed significant prognostic value for most substage divisions (P = 0.03-0.0002) except for IB-IC and IIB-IIC combinations (P > 0.33). Further analyses revealed no significant differences between IB-IC and IIB-IIC patients in several prognostic parameters such as age, histologic grade, cell type, and amount of residual disease. CONCLUSIONS: These data support the current FIGO staging system. However, Substages IB-IC and IIB-IIC should be combined to respective single substages.

Adult↗

PubMed1993

In vitro potentiation of radiation cytotoxicity by recombinant interferons in cervical cancer cell lines.

BACKGROUND: This investigation, which evaluates the combination of radiation and interferon, bridges two clinical treatments of cancer. Radiation therapy (RT) is an integral part of cervical cancer treatment; interferons (IFN), however, are classified as modifiers of biologic response. The authors evaluated the radiation-modulation effects of recombinant alpha-IFN and beta-IFN on two different human cervical cancer cell lines: ME-180 and SiHa. The radiation sensitivity based on the cell growth rate (logarithmic growth phase versus confluence) was also evaluated. METHODS: Control cells and cells pretreated with either alpha-IFN or beta-IFN were exposed to RT at doses of 0, 2, 5, 10, and 15 Gy. The pretreated cells received IFN at doses of 100, 500, 1000 and 5000 IU/ml for 24 hours. The adenosine triphosphate bioluminescence assay was used to measure the surviving fractions after 7 days of incubation. The data were analyzed using the linear-quadratic model and the radiosensitivity index D. The combined effects of IFN and RT on cytotoxicity were evaluated using the synergistic interaction formula for anticancer agents. RESULTS: The ME-180 and SiHa cell lines had the same mean inactivation D values of 13.2 when radiated at confluence. Irradiation of ME-180 and SiHa cells in the logarithmic growth phase resulted in mean inactivation D values of 7.5 and 10.2, respectively. Enhanced radiosensitivity was observed in all IFN-RT combinations. Synergism was observed in the majority of experiments. CONCLUSIONS: Recombinant alpha-IFN and beta-IFN potentiate the radiotoxicity of two cervical cancer cell lines. ME-180 cells were less sensitive to IFN alone than were SiHa cells, but they showed higher a radiosensitizing effect from both IFN. Proliferating cells were more sensitive than confluent cells to RT by itself and to RT-IFN combinations.

Carcinoma, Squamous Cell↗

PubMed1993

Enhancement of progesterone receptor levels by interferons in AE-7 endometrial cancer cells.

BACKGROUND: Interferon (IFN) has been reported to increase hormone receptor expression in breast cancer cells and to sensitize them to antiproliferative hormones. Endometrial cancer cells with high progesterone receptor (PR) level respond better to progesterone therapy than cells with either low or absent PR level. The effect of four different interferons (alpha and beta, both natural [n] and recombinant [r]) on cell proliferation and steroid receptor levels was investigated in the PR positive AE-7 human endometrial cancer cell line over a period of 12 days. METHODS: Cells were exposed to 10,100 and 1000 IU/ml of each IFN either for 3 days or continuously for 12 days. Hormone receptors were determined by the monoclonal enzyme immunoassay. Chemosensitivity was evaluated with the adenosine triphosphate-cell viability assay. RESULTS: AE-7 has a low level of estrogen receptors, which was not significantly affected by IFN exposure. The four IFN showed significantly enhanced PR levels over 12 days in both the 3-day and continuous-exposure experiments. No significant difference of PR enhancement was observed between 3 days and continuous exposure to IFN. This increase of receptors did not appear to be dose related. IFN enhanced PR level to a maximum level of about two times control cells. IFN did not produce significant cytotoxicity. Antiproliferative activity was observed with nIFN beta and rIFN beta at 1000 IU/ml dose in continuous-exposure experiments, which showed survival values of 79% and 69% respectively, compared with control at day 12. CONCLUSIONS: These preliminary data on PR expression modulation support other studies, which have shown that IFN modulate hormone receptor expression and, therefore, may play a role in the treatment of endometrial cancer.

Adenosine Triphosphate↗

PubMed1993

Evidence of tumor heterogeneity in cervical cancers and lymph node metastases as determined by flow cytometry.

BACKGROUND: The incidence and significance of tumor heterogeneity in primary tumors and metastatic lymph nodes were investigated in Stage IB-IIA cervical cancers. METHODS: Paraffin-embedded tissues from 96 radical hysterectomy specimens were dewaxed, disaggregated, and subjected to dual parameter flow cytometry. Three-dimensional histograms were generated to delineate different tumor populations. A DNA index difference of at least +/- 0.15 was used to define tumor heterogeneity. RESULTS: Mean DNA index difference of various tumor populations was 0.29 +/- 0.13. Among 69 patients with normal lymph nodes, there were 12 patients (incidence, 17.4%) with tumor heterogeneity in the primary tumors. Of 27 patients with metastatic lymph nodes, 5 (incidence, 18.5%) had evidence of tumor heterogeneity in the primary tumor, and 18 of 47 (incidence, 38.3%) had tumor heterogeneity in metastatic lymph nodes. When using DNA index to determine clonal origin of metastatic lymph nodes, as many as 60% of the metastases could not be traced to the primary tumor. Tumor heterogeneity was associated with a 40% reduction in median survival time. However, because of the small number of patients with tumor heterogeneity, statistical analyses did not show prognostic significance. CONCLUSIONS: Tumor heterogeneity appeared to be a common characteristic of early cervical carcinoma. Additional study is needed to fully evaluate its prognostic value.

Adenocarcinoma↗

PubMed1993

Radical hysterectomy for invasive cervical cancer. A 25-year prospective experience with the Miami technique.

BACKGROUND: The Miami modification of the traditional Wertheim-Meigs radical hysterectomy was used to treat Stage IB-IIA cervical cancer in a 25-year prospective study involving 978 patients. METHODS: The modifications included: vaginal reconstruction and closure using bladder and rectosigmoid serosa, retroperitoneal drainage through abdominal suction catheters, and suspension of the denuded ureters with the ipsilateral obliterated hypogastric artery. RESULTS: The overall corrected 5-year survival rate was 90.1%, with a surgical mortality rate of 1.4% and an overall urinary fistula rate of 1.4%. This fistula rate was significantly better than a 4.4% incidence rate in a literature survey. Although not measured, the Miami modification appeared to lengthen the vagina. CONCLUSIONS: Therefore, it was concluded that radical hysterectomy with the Miami modifications can be done safely in most patients with Stage IB-IIA cervical cancer.

Adenocarcinoma↗

PubMed1993

Chemosensitivity testing in ovarian cancer.

Most patients with ovarian cancer currently are treated primarily with surgery and chemotherapy. Drug selection usually is not based on individualized in vitro sensitivity studies but on reported response rates of clinical trials. Attempts to include in vitro chemosensitivity testing into the management of ovarian cancer have been disappointing to clinicians. Tumor cells from fresh human ovarian cancer do not grow well under artificial in vitro growth conditions. The selection of cells that happen to proliferate in vitro (e.g., human tumor clonogenic assay) has resulted in low plating efficiencies (0.001-0.1% of plated cells). The vigorous mechanical and enzymatic tumor disaggregation, done to obtain a single-cell suspension, further reduces the number of cells that grow in vitro, resulting in low overall evaluability rates of 40-70% for the human tumor clonogenic assay. At the University of Miami, a new in vitro chemosensitivity assay was developed that detected the decrease in total tumor cell viability by measuring intracellular adenosine triphosphate as a function of in vitro drug response. Preliminary data on 31 tumor tissues from patients, which was evaluated with this method, showed a sensitivity of 92% and a specificity of 100%. Since these initial studies, data were gathered on more than 150 fresh gynecologic tumor specimens to evaluate single drugs and drug combinations at five concentrations (range, 10-500% of reported peak plasma concentrations). The evaluability rate for ovarian tumors was more than 90%. Some tumors showed almost complete cell kill at the lowest drug concentration; others had only a limited response at the highest level. Drug-response patterns also were variable for combined drug exposure. These findings underscore the heterogeneity of drug response in morphologically similar tumors and the importance of characterizing individual chemosensitivity profiles for patients before drug treatment.

Drug Screening Assays, Antitumor↗

PubMed1993

Functional characteristics and follow-up of the continent ileal colonic urinary reservoir. Miami pouch.

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Anastomosis, Surgical↗

PubMed1993

Demonstration of an S phase population of cells without DNA synthesis generated by cisplatin and pentoxifylline.

Dual parameter flow cytometry measuring DNA and BrdUrd uptake in "stripped" nuclei was used as a sample preparation procedure. The utility of this method is demonstrated in a human ovarian cell line (BG-1) by two parameter flow cytometric analysis of DNA and bromodeoxyuridine (BrdUrd) incorporated into the DNA. BG-1 cells, treated with cisplatin followed by constant exposure to pentoxifylline, produce G0/G1, S phase, and G2/M perturbations. The G0/G1 population is greatly diminished. Large numbers of cells are distributed in S phase in which a large portion is incapable of DNA synthesis. The G2/M perturbations show a continually increasing block over a time course of 168 h. The identification of two types of S phase cells (DNA synthesizing and DNA nonsynthesizing) is clearly shown with the use of BrdUrd incorporation as a second parameter in addition to flow cytometric analysis of DNA. This increase in the non-DNA-synthesizing S phase population corresponds to an enhancement of cytotoxicity when cells are treated with the combination of cisplatin and pentoxifylline. It is felt that this technique provides a useful method to investigate the dynamics of the cell cycle perturbations affected by modulators of chemotherapeutic agents.

Bromodeoxyuridine↗

PubMed1993

Preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy.

This study reports our preliminary experience with a modified Tenckhoff catheter for intraperitoneal chemotherapy, primarily designed to be larger, longer, and have more perfusion holes. There were 137 catheters implanted in 125 ovarian cancer patients from June 1988 to December 1990, among which 116 were actually used for intraperitoneal chemotherapy. A total of 559 cycles of intraperitoneal chemotherapy was given with a range of 1 to 16 uses per catheter. There were seven infections (6.0%), four inflow obstructions (3.4%), three bowel perforations (2.6%), and one leakage (0.8%). Among patients with catheter infection, three had delayed bowel perforation. Although the incidence of inflow obstruction was reduced from 5.5 to 3.4%, the improvement did not reach statistical significance. The frequency of delayed bowel perforation and infection were similar to the literature experience of other catheters. An unused catheter should be removed to avoid this serious complication. Further study is needed to evaluate fully the performance of this catheter system.

Antineoplastic Agents↗

PubMed1993

Application of the adenosine triphosphate-cell viability assay in human breast cancer chemosensitivity testing: a report on the first results.

Chemosensitivity testing in vitro of breast cancer has been difficult because of small tumour volume, an even smaller yield of viable cells after disaggregation, and the low evaluability rate and sensitivity of current assays. We have employed an alternative approach that quantitates intracellular adenosine triphosphate (ATP) as a measure of cell viability. This ATP-cell viability assay (ATP-CVA) determines in vitro tumor cell viability after exposure to chemotherapeutic agents in comparison to untreated controls following 6 days of incubation. Sixty-one fresh breast cancer specimens upon testing yielded an evaluability rate of 95%. Forty-seven of the tumors were untreated primary breast cancers, the remaining 14 were from patients with metastatic disease. Correlations of in vitro drug sensitivity with in vivo response were obtained for 17 treatment regimens in 14 patients with metastatic breast cancer. The level of sensitivity was 90% and the specificity 86%. These preliminary data demonstrated the ATP-CVA to be a practical in vitro approach to breast cancer testing. It will require a larger clinical study for confirmation.

Adenosine Triphosphate↗

PubMed1993

Radiosensitization of uterine cancer cell lines by cytotoxic agents.

Radiotherapy remains an integral part of uterine cancer therapy. Overcoming radioresistant tumors by sensitizers continues to be a prime objective in radiotherapy research. In this study, the effects of five cytotoxic agents on two radiosensitive and four radioresistant uterine cancer cell lines were investigated. The ATP bioluminescence was used to measure surviving fractions. Data analysis was done using the linear quadratic model and radiosensitivity index D. Both AN3 and SKUT1B were radiosensitive with Ds of 1.73 and 1.72 Gy, respectively. The resistant cell lines had the following D values: AE7, 3.50; ECC, 6.61; HEC1A, 4.59; and HEC1B, 13.49 Gy. The average radiosensitization effects for various drugs were measured by reduction of D: DXR 45 +/- 7, DDP 40 +/- 9, 5FU 55 +/- 10, MITO 59 +/- 14, and HU 1.7 +/- 7%. Except for HU, Wilcoxon analyses revealed that these sensitizing effects were significant with P < 0.02. In summary, Adriamycin, 5-fluorouracil, cisplatin, and mitomycin-C have the potential to be radiosensitizers in uterine cancer cell lines.

Adenosine Triphosphate↗