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Biomedical subjects

J S Berek

Publications and source records attributed to J S Berek.

At least 109 records · Page 6Linked to original sources
PubMed1989

Randomized trial of cyclophosphamide plus cisplatin with or without doxorubicin in ovarian carcinoma: a Gynecologic Oncology Group Study.

A randomized clinical trial was conducted in women with stage III ovarian carcinoma (less than or equal to 1 cm residual lesions), using cyclophosphamide plus cisplatin (CP) with or without doxorubicin. There were 349 evaluable patients, of whom 176 received CP while 173 patients received CP plus doxorubicin (CAP). Hematologic toxicity was almost identical. There was no significant difference in progression-free interval (PFI) (median, 22.7 months and 24.6 months), frequency of negative second-look laparotomy (30.2% and 32.8%), or survival (median, 31.2 months and 38.9 months) between CP and CAP, respectively. Thus, doxorubicin in the dose schedule employed does not improve combination chemotherapy of optimal stage III ovarian carcinoma. Several other findings, independent of treatment arm, were of interest. There was a significant difference in PFI and survival by residual disease category (yes v no) and by grade of differentiation (1 v 2 + 3). In multivariate analysis, age, residual disease at entry, cell type (clear cell carcinoma), and time from surgery to initiation of chemotherapy were significant predictors of survival. There was no difference in outcome comparing those who refused second-look with those who had a second-look.

Adult↗
PubMed1989

Lymphocyte activation by recombinant interleukin-2 in ovarian cancer patients.

Peripheral blood lymphocytes from 42 patients and peritoneal cavity lymphocytes from eight patients with advanced ovarian carcinoma were tested for lymphokine-activated killer lymphocyte cytotoxicity against several ovarian carcinoma lines before and after exposure to recombinant interleukin-2 in vitro for 3-5 days. Only four of 42 (9.5%) of peripheral blood lymphocytes and zero of eight (0%) of peritoneal cavity lymphocytes had spontaneous cytotoxicity (greater than 20%) against the ovarian carcinoma lines. After in vitro exposure to recombinant interleukin-2, 41 of 42 (98%) of patients' blood lymphocytes showed a two- to fivefold increase in cytotoxicity against K562 (a lymphoblastoid human target), and 40 of 42 (95%) demonstrated lymphokine-activated killer cytotoxicity (greater than 20%) to the ovarian carcinoma lines. Lymphokine-activated killer activity against fresh allogeneic cell lines was variable, although most patients' peripheral blood lymphocytes (70%) had significant cytotoxicity. By contrast, incubation of patients' peritoneal cavity lymphocytes with recombinant interleukin-2 in vitro did not result in the generation of lymphokine-activated killer cell activity against K562 or ovarian cell lines. Peritoneal lymphocytes did produce lymphokine-activated killer cells in the presence of OK432 in half of the patients tested. The presence of autologous serum during recombinant interleukin-2 activation with blood lymphocytes had an augmentative effect on the resulting lymphokine-activated killer cytotoxicity in two of 20 patients, a suppressive effect in four of 20, and no effect in the other 14 of 20 patients tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1989

Synergistic effect of combined intraperitoneal cisplatin and cytosine arabinoside in a murine ovarian cancer model.

The chemotherapeutic combination of cisplatin and cytosine arabinoside has synergy in vitro. We used a murine ovarian teratocarcinoma in C3HeB/FeJ mice to evaluate these drugs for synergy in vivo. Several dose-response schedules and various sequences were tested to determine the optimal delivery schedule. Survival of control mice injected with 10(4) murine ovarian teratocarcinoma was 28 days. Tumor-bearing mice treated with intraperitoneal cisplatin alone had significantly prolonged survival, whereas intraperitoneal cytosine arabinoside alone did not prolong survival. Repeated doses of cytosine arabinoside every 24 hours for 4 days resulted in minimal prolongation of survival. Simultaneous one-time administration of cisplatin and cytosine arabinoside resulted in synergy as measured by survival, with 50% of mice surviving at 80 days. Combined simultaneous administration of cisplatin and cytosine arabinoside daily for 3 days resulted in 100% survival at 120 days. Both cisplatin and cytosine arabinoside have an outstanding pharmacokinetic advantage when given intraperitoneally. A clinical trial of these drugs with a 3-day schedule is warranted.

Animals↗
PubMed1988

Intraperitoneal administration of human recombinant interferon-alpha in patients with ovarian cancer: effects on lymphocyte phenotype and cytotoxicity.

Eleven patients with persistent Stage III ovarian cancer, documented at second look laparotomy, received i.p. human recombinant interferon-alpha (5-50 x 10(6) units/week). Prior to immunotherapy, patients' peritoneal cell lymphocytes (PCLs) contained decreased proportions of Leu-7+ and Fc-receptor+ cells and almost nondetectable natural killer (NK) and antibody-dependent cell cytotoxic (ADCC) activity. In contrast, patients' peripheral blood lymphocytes (PBLs) contained normal proportions of lymphocyte subsets and cytotoxic activity compared to control donor PBLs. During therapy, there was a concurrent increase in PCL Leu-7+ cells and NK lysis. Both peaked predictably at 24 h after each treatment, regardless of the dose injected, and usually returned to baseline by Day 7 of each weekly cycle. PCL NK enhancement was striking, usually increasing from 2-6% (effector:target ratio, 25:1) to over 30% lysis. Enhancement of PCL ADCC was less impressive. PCLs of several patients developed lytic activity towards NK-resistant Raji targets. During therapy, patients' PBLs demonstrated: (a) modestly enhanced NK lysis at Day 4 of each cycle, and; (b) no development of Raji lysis. These data clearly demonstrate the efficacy of i.p. interferon in activation of peritoneal NK activity. However, increased NK lysis did not correlate with individual tumor responses in this cohort of patients.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1988

Sensitivity of fresh and cultured ovarian tumor cells to tumor necrosis factor, interferon-alpha 2, and OK-432.

The in vitro sensitivity to rTNF, rIFN-alpha 2, and OK-432 of 11 freshly derived human ovarian tumors and 2 established tumor cell lines was examined in a cytotoxic assay using the 51 Cr release test. Nine fresh lines were sensitive to rTNF, 8 to OK-432, and only 2 were sensitive to rIFN-alpha 2. Cytotoxicity by rIFN-alpha 2 was of lesser magnitude than the cytotoxicity mediated by rTNF or OK-432. The time of exposure and the concentration of BRM required for maximal cytotoxicity varied from line to line. Two fresh tumor cell lines and 1 established cell line (PA-1) were sensitive to all 3 BRMs, while 2 other FOCs and 1 cell line (SKOV-3) were resistant to all BRMs. The remaining FOC showed an intermediate degree of sensitivity. These results demonstrate the existence of heterogeneity of ovarian carcinoma tumor cell lines to lysis by BRMs. Among the FOCs, the 2 endometrioid carcinomas tested were highly sensitive to rTNF, whereas the serous carcinomas were more sensitive to OK-432. Low grade tumors were more sensitive to BRM than high grade tumors, and tumor extension did not correlate with sensitivity to the BRM. When tumor targets were exposed to more than 1 BRM added either simultaneously or sequentially, the net cytotoxic effect achieved was usually inferior to the sum cytotoxicity obtained by each BRM alone. Furthermore, rTNF and OK-432 were cytostatic to most ovarian tumor cell lines examined. The results of this study demonstrate that certain BRMs exert a direct effect on fresh ovarian tumor cells independently of host factors. These findings suggest that in vitro screening of a patient's tumor cells for sensitivity to a particular BRM prior to therapy could be beneficial for the proper identification of patients most likely to benefit from the treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Preoperative evaluation of serum CA 125 levels in premenopausal and postmenopausal patients with pelvic masses: discrimination of benign from malignant disease.

CA 125 levels were measured in 158 patients with palpable pelvic masses who were about to undergo diagnostic laparotomy. When the 68 patients found to have cancer were compared with the 90 patients with benign disease, those with malignancies were significantly older, were more frequently postmenopausal, and had significantly higher values of serum CA 125. Patients with benign pelvic masses had CA 125 levels greater than 65 U/ml in 8% of cases, whereas those with malignancies had CA 125 levels greater than 65 U/ml in 75% of cases. If only those patients who had frankly malignant, primary, nonmucinous epithelial ovarian carcinomas were considered, CA 125 levels greater than 65 U/ml predicted malignancy with a sensitivity of 91% for all patients. Greater sensitivity and specificity were observed in the postmenopausal subgroup than in the premenopausal subgroup. In the postmenopausal group with a 63% prevalence of ovarian cancer the predictive positive value was 98% and the predictive value negative was 72%. In a premenopausal population with a 15% prevalence of ovarian cancer the predictive value for a positive test was 49%, while the predictive value for a negative test was 93%.

Adolescent↗
PubMed1988

Peritoneal cytology of ovarian cancer patients receiving intraperitoneal therapy: quantitation of malignant cells and response.

An analysis was performed of malignant and host cells found in peritoneal fluids obtained during intraperitoneal chemotherapy and immunotherapy in patients with ovarian cancer. The concentration of malignant cells and the surgically documented response to the intraperitoneal treatment were correlated. Twenty-three patients were treated with intraperitoneal cisplatin or alpha-2 interferon (rIFN-alpha 2) after persistent carcinoma was documented at second-look laparotomy. Six patients (26%) had a complete response to therapy, and all of these patients had a malignant cell concentration of less than 10(2)cells/cm2/dL. No responses were seen in patients whose initial malignant cell concentration was greater than 10(3)cells/cm2/dL. Among patients treated with intraperitoneal alpha-interferon, five of 11 whose initial concentration of malignant cells was less than 10(2) cells/cm2/dL responded to therapy, whereas none of the patients whose malignant cell concentration was 10(2) cells/cm2/dL or greater responded. In patients treated with intraperitoneal cisplatin, the initial concentration of malignant cells associated with any surgically documented response was less than 10(3)cells/cm2/dL. A host mesothelial reaction was prominent after intraperitoneal alpha-interferon, but not observed in women treated with intraperitoneal cis-platin. The fluctuating pattern of peritoneal white blood cells documented during therapy did not correlate with response. THe evaluation of peritoneal cytology specimens during intraperitoneal chemotherapy should include a quantitative assessment of malignant cells and reactive mesothelial cells in order to reflect more accurately the histologically documented findings. Initial quantitative cytology appears to correlate with the likelihood of a surgically documented response to intraperitoneal therapy.

Aged↗
PubMed1988

Controversies in the management of cervical adenocarcinoma.

Adenocarcinoma of the uterine cervix appears to be more prevalent now than a decade ago, and currently constitutes 10-20% of invasive cervical cancers. Because precursor lesions arise within the endocervical canal, identification and diagnosis of invasive disease is often more difficult than for squamous carcinoma. There is disagreement regarding the optimal treatment of adenocarcinoma. Adenocarcinoma may have a poorer prognosis than squamous carcinoma because it may be more difficult to detect and because it tends to metastasize earlier in its course. The controversies in the diagnosis and management of adenocarcinoma and adenosquamous carcinoma of the uterine cervix are reviewed.

Adenocarcinoma↗
PubMed1987

Rhabdomyosarcoma of the uterine cervix. Sarcoma botryoides.

Twenty-one cases of sarcoma botryoides of the uterine cervix, including four previously unreported cases, are reviewed. The age of the patients ranged from 5 months to 48 years, with a peak incidence in the group aged 14 to 18 years. Eighty percent of the patients are alive, with a mean follow-up period of 68 months. Seventy-five percent of the patients had Group I disease, of whom 88% are alive. Eleven of 14 patients (79%) receiving vincristine and dactinomycin based chemotherapy are alive. There were five patients with recurrent disease (24%) of whom two (40%) are alive. The prognosis for cervical sarcoma botryoides is similar to that of other female genital tract embryonal rhabdomyosarcomas. Primary therapy should consist of vincristine and dactinomycin based chemotherapy. Surgery should be guided by the response to initial chemotherapy and should attempt to conserve the function of the bladder, rectum, vagina, and ovaries.

Adolescent↗
PubMed1987

Distant metastases in epithelial ovarian carcinoma.

A review of 255 patients with epithelial ovarian carcinoma revealed that metastases consistent with Stage IV disease developed in 97 patients (38.0%) at some time during the natural history of their disease. Malignant pleural effusions developed in 63 patients (24.7%), and their median survival (from the time of diagnosis of the effusion) was 6 months. Parenchymal liver metastases developed in 24 patients (9.4%; median survival, 5 months); parenchymal lung metastases in 18 patients (7.1%; median survival, 8 months); distant lymph node metastases in 18 patients (7.1%; median survival, 9 months); subcutaneous nodules in nine patients (3.5%; median survival, 12 months); a malignant pericardial effusion in six patients (2.4%; median survival, 2.3 months); central nervous system metastases in five patients (2%; median survival, 1.3 months); and bone metastases in four patients (1.6%; median survival, 4 months). Patients with Stage IV disease at the time of diagnosis had a median survival of 9.1 months, while patients with a delayed occurrence of distant metastases had a median survival of only 4 months from the time of diagnosis of the distant metastases. Significant risk factors for distant metastases were malignant ascites, peritoneal carcinomatosis, large metastatic disease within the abdomen, and retroperitoneal lymph node involvement at the time of the initial surgery. The significance of positive retroperitoneal nodes and bulky upper abdominal disease has important therapeutic implications.

Adolescent↗
PubMed1987

Prognostic significance of DNA ploidy and morphometric analyses of adenocarcinoma of the uterine cervix.

In an effort to improve the prognostic accuracy of the histologic criteria used for cervical adenocarcinomas, the nuclear DNA ploidy levels, means and standard deviations of nuclear areas and amounts of lumen and neoplastic tissue were quantitated. Useful thresholds in discriminating recurrent disease, as identified by logistic regression analysis, included a DNA ploidy level of 3.0 N, a percent of lumen of 34.6% and nuclear area mean and standard deviation of 53.1 sq micron and 20.1 sq micron, respectively. These parameters should provide useful guidelines in the visual assessment of histologic features that have prognostic significance.

Adenocarcinoma↗
PubMed1987

Diagnostic problems of in situ and invasive adenocarcinomas of the uterine cervix.

In this study of 58 cervical in situ and invasive adenocarcinomas, the diagnostic accuracy of cervical biopsies was found to be closely related to the extent and the degree of differentiation of the neoplasm. Biopsies of in situ and early, well-differentiated adenocarcinomas were often limited in amount, precluding an accurate assessment of stromal invasion. In such cases, a comprehensive sample, e.g., by conization, was required to establish the diagnosis. Invasive adenocarcinoma could be distinguished from the in situ change by the loss of branching pattern of normal endocervical glands, a marked variation in the size and shape of the glands, and a complex papillary or solid growth pattern. The presence of a desmoplastic reaction further supported the invasive nature of the neoplasm.

Adenocarcinoma↗
PubMed1987

Intraperitoneal cis-platinum as salvage therapy for refractory epithelial ovarian cancer.

Eighteen patients with residual epithelial ovarian cancer at second-look laparotomy were treated with a combined total of 210 cycles of intraperitoneal cis-platinum. Sixteen patients had previously received cis-platinum containing combination chemotherapy systemically. Seven patients had microscopic residual disease at the start of intraperitoneal therapy, eight had macroscopic disease of 5 mm in diameter or less, and three had disease of 6-10 mm in diameter. The drug was administered weekly in 2 L of Ringer's lactate solution via an indwelling Tenckhoff catheter, and the dose ranged from 30-270 mg per cycle (median 120 mg). The dwell time was 20 minutes. After 12 cycles, response was assessed by open laparoscopy (six patients), laparotomy (eight patients), or peritoneal cytology (three patients). One patient developed distant metastases. Local and systemic toxicity was mild. Delays of therapy were necessary for eight of the 210 cycles because of hematologic toxicity. Of the 15 patients available for pathologic evaluation, four (26.6%) had a complete response and two (13.3%) had a partial response. Results of this pilot study suggest a possible role for intraperitoneal cis-platinum in the management of carefully selected patients with epithelial ovarian cancer.

Adult↗
PubMed1986

The CA 125 assay as a predictor of clinical recurrence in epithelial ovarian cancer.

Serum CA 125 levels were obtained from 55 women with epithelial ovarian cancer before a second-look surgical procedure and serially thereafter. All patients were clinically and radiographically free of tumor at the time of the second-look operation and were followed to clinical recurrence. Median follow-up was 12 months. CA 125 levels obtained at the second-look operation had a sensitivity and specificity for predicting clinical recurrence of 94% and 88%, respectively. Patients with an elevated CA 125 level (greater than or equal to 35 U/ml) had a 60% chance of clinical recurrence within 4 months, while patients with levels less than 35 U/ml had a 5% chance of clinical recurrence over the same time period. Serial CA 125 levels obtained after second-look operations were strong predictors of clinical outcome, and distinctly different monitoring profiles were observed among those patients remaining clinically free of tumor and those suffering clinical recurrence. The CA 125 assay became elevated (greater than or equal to 35 U/ml) before clinical recurrence in 94% of 35 cases with a median lead time of 3 months. The CA 125 assay identifies patients destined to suffer a clinical recurrence and provides a warning measurable in months. This may have important implications for therapy.

Adult↗
PubMed1986

Phase II trial of cisplatin in advanced or recurrent cancer of the vagina: a Gynecologic Oncology Group Study.

Twenty-six patients with advanced or recurrent cancer of the vagina no longer amenable to control with surgery and/or radiotherapy were entered into a phase II study of cisplatin 50 mg/m2 intravenously every 3 weeks. Two were deemed ineligible because of a primary site of origin other than vagina. Two were deemed inevaluable, one because of the lack of measurable disease and the other because she never received drug. The remaining 22 included a variety of histologies (16 squamous cell carcinomas, 2 adenosquamous carcinomas, 1 clear cell carcinoma, 1 leiomyosarcoma, and 2 carcinomas not otherwise specified). One complete responder was observed among the 16 patients with squamous cell carcinoma. Adverse effects were tolerable and were essentially those reported in other series. These results suggest that cisplatin has insignificant activity in advanced or recurrent squamous cell carcinoma of the vagina at least at the dose and schedule tested. No comment can be made regarding the activity of cisplatin in other histologies.

Carcinoma, Squamous Cell↗