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J S Berek

Publications and source records attributed to J S Berek.

At least 37 records · Page 2Linked to original sources
PubMed1998

Progress in ovarian cancer.

The management of advanced ovarian cancer relies on appropriate surgical cytoreduction in conjunction with appropriate adjuvant chemotherapy. In the past year several studies have continued to support aggressive cytoreduction at the initial operation, including for stage IV disease, as well as in a second-look setting. Ongoing research has identified several agents active in ovarian cancer, yet the optimal first-line regimen has yet to be developed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Reducing loss-to-follow-up among women with abnormal Pap smears. Results from a randomized trial testing an intensive follow-up protocol and economic incentives.

OBJECTIVES: This study evaluates the efficacy of two interventions designed to reduce loss-to-follow-up among women with abnormal Pap smears. METHODS: The two interventions were evaluated in two large public hospitals using a randomized 2 x 2 factorial design. One intervention involved an intensive follow-up protocol that relied on multiple attempts (mail and telephone) to contact the patient. The second intervention provided patients with economic vouchers to offset out-of-pocket expenses associated with the follow-up visits. Loss-to-follow-up was addressed by medical chart reviews and telephone interviews. RESULTS: The study population (n = 1453) was primarily Hispanic, married or otherwise living with a significant other, relatively young in age, and with no source of payment for health care. Overall, 30% of the total sample was loss-to-follow-up (i.e., no return visits). Among patients assigned to the control condition, loss-to-follow-up was 36.1% compared with 27.8% for the intensive follow-up condition, 28.8% for the voucher condition, and 29.0% for the intensive follow-up plus voucher condition. Both intervention conditions significantly improved follow-up rates. The odds ratio for intensive follow-up was 1.56 compared with 1.50 for the voucher intervention. The combined intervention condition (intensive follow-up x voucher program) did not have a significant effect after taking into account the main effects of the two interventions. Correlates of loss-to-follow-up included age (younger women had lower return rates), race/ethnicity (African American women had lower return rates), live-in relationship (women who were not married or living as married had lower return rates), and severity of the abnormal Pap smear (less severe abnormalities were associated with lower return rates). CONCLUSIONS: Both interventions were associated with moderate reductions in loss-to-follow-up in this underserved population. The implications of these findings are discussed relative to implementing cervical cancer control programs within state and local health departments.

Adult↗
PubMed1997

Gene therapy for ovarian cancer: development of novel treatment strategies.

In the last decade, advances in molecular biology have lead to the development of techniques that permit the manipulation of mammalian cell DNA for diagnostic and therapeutic purposes. Gene therapy has subsequently evolved as a treatment option in patients with malignancies. In this article, we have summarized current strategies in gene therapy for ovarian cancer.

Journal Article↗
PubMed1996

Vascular endothelial growth factor expression is not regulated by estradiol or medroxyprogesterone acetate in endometrial carcinoma.

OBJECTIVE: To determine whether the expression of vascular endothelial growth factor (VEGF) is altered by treatment in an in vivo tumor with 17 beta-estradiol (E2) or medroxyprogesterone acetate (MPA). METHODS: A well-differentiated endometrial carcinoma tumor was isolated from a patient and explanted into the dorsal skin of ovariectomized nude mice, from which it was serially passaged in vivo. The explanted tumor retained all the properties of the original tumor, including estrogen and progesterone receptor expression and growth promotion and inhibition by E2 and MPA, respectively. The mice were treated with continuous E2 administration followed by treatment with either a single intramuscular administration of 2 mg MPA or weekly administrations of 2 mg MPA. Untreated tumor-bearing mice served as controls. The tumors were harvested at 0 to 21 days from first MPA administration. RNA from the tumors was isolated and VEGF expression was determined by Northern analysis. RESULTS: VEGF was expressed in the absence of treatment with E2 or MPA, and expression was unaltered by continuous treatment with E2. Additional treatment with a single does of MPA did not alter expression at Days 1, 2, 3, 7, 14, and 21, and additional treatment with E2 or E2 + MPA. Regulation of VEGF expression is not a mechanism by which these hormones exert their growth effects on endometrial tumors.

Actins↗
PubMed1996

Dysgerminoma: the role of conservative surgery.

Twenty-five cases of pure ovarian dysgerminoma treated at UCLA Medical Center between 1958 and 1992 were reviewed retrospectively. Patterns of recurrence and overall survival were analyzed with regard to primary surgery (conservative versus nonconservative), use of adjuvant therapy, and stage of disease. Fourteen patients (56%) underwent conservative surgical therapy defined as preservation of the contralateral ovary, 10 patients (40%) had nonconservative primary surgery, and one patient (4%) had chemotherapy as primary treatment. Three patients (12%) received adjuvant chemotherapy and nine patients (36%) received postoperative radiation therapy. Fifteen patients (60%) had stage I disease, four (16%) stage II, and three each (12%) had stage III and IV disease. Nine patients (36%) experienced recurrence of disease. Seven of these nine patients (78%) had stage I disease and all seven had undergone conservative primary surgery with preservation of the contralateral ovary. Six of the seven had received no adjuvant therapy. Only one of these seven patients experienced recurrence in the preserved ovary. She was found to have a dysgenetic ovary and an XY karyotype. Three patients with recurrent disease had received radiation therapy after primary surgery. Twenty patients (80%) were alive without disease at follow-up, two patients (8%) were alive with disease, and three (12%) had died of disease. There was no statistically significant difference in recurrence rates between those patients treated with conservative surgery and those treated with nonconservative surgery, although the total number of patients with recurrences was greater in the former group. Our data suggest that a conservative surgical approach is the preferred treatment in patients with pure dysgerminoma of the ovary who desire future fertility. Lack of adjuvant chemotherapy or radiation therapy, rather than type of initial surgery, may be associated with a higher risk of recurrence.

Adolescent↗
PubMed1996

Mixed mesodermal sarcoma of the ovary in a young patient.

Mixed mesodermal tumors (MMT) of the ovary are rare and have a poor prognosis. This ovarian malignancy usually occurs in postmenopausal women. We report an unusual ovarian MMT in a young woman given treatment similar to one used for ovarian germ cell malignancies. We believe this is the youngest patient reported with an homologous MMT of the ovary.

Adult↗
PubMed1996

Evidence for a unifocal origin in familial ovarian cancer.

OBJECTIVE: The purpose of this investigation was to determine the pattern of loss of heterozygosity in multiple tumor sites from familial ovarian cancer cases. If ovarian cancer arises focally in one ovary and then metastasizes to other sites, a similar pattern should be seen in all tumor sites. However, if ovarian cancer arises multifocally throughout the peritoneal cavity, a different pattern of loss would be expected among the different sites. STUDY DESIGN: The presence or absence of loss of specific alleles for 9 loci on chromosomes 1, 6, 11, 13, 16, and 17 was determined in multiple tumor sites from 12 familial ovarian cancer cases. RESULTS: The frequency of loss of heterozygosity was as follows: chromosome 17 (100%), chromosome 13 (82%), chromosome 6 (80%), chromosome 16 (73%), chromosome 1 (57%), and chromosome 11 (22%). In every case an identical pattern was present for at least one locus. In four cases loss of the same allele was present in tumor from the ovary and all metastatic sites for all informative loci. In the remaining eight cases loss of the same allele for one to five (mean three) loci was detected. CONCLUSIONS: The pattern of loss of heterozygosity in the 12 familial ovarian cancers included in this investigation favors a unifocal origin of disease. A dual primary origin could not be absolutely excluded in 3 cases. High frequencies on chromosomes 17q and 13 suggest that loss of whole or part of these chromosomes is important in ovarian carcinogenesis.

Alleles↗
PubMed1995

Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection.

BACKGROUND: The use of serum tumor markers for the early detection of ovarian cancer has been limited because of their low sensitivity and low positive predictive value. CA 125 levels are elevated in only about one half of women with Stage I ovarian cancer, thus researchers have focused on using the serial measurement of complementary markers to improve the sensitivity, specificity, and positive predictive value of this approach for screening. METHODS: Multiple serum markers have been analyzed in women with early stage epithelial ovarian cancer. CA 125, CA 15-3, C19-9, CA 54-61, CA 72-4, CEA, HMFG2, IL-6, IL-10, LSA, M-CSF, NB70K, OVX1, PLAP, TAG72, TNF, TPA, and UGTF have been studied alone and in combination in this setting. Complementarity and logistic regression analyses have been performed to assess those markers with the highest likelihood of improving sensitivity and specificity for early detection. Serial analysis of a second-generation CA 125 measuring the intercept (initial level) and slope (change of levels over time) can be used to discriminate malignant cases from benign and normal cases. RESULTS: Analyses have shown that the serial measurement of the new, more sensitive CA 125 has a high sensitivity (83%), specificity (99.7%), and positive predictive value (16%) for the early detection of ovarian cancer. OVX1 used in combination with CA 125 provides the best complementarity. Serial measurements of the two markers have sensitivities in the range of that for transvaginal ultrasonography. CONCLUSION: The serial measurement of complementary serum markers can improve the use of marker screening for epithelial ovarian cancer. With the use of several different methods of analysis, it has been shown that this approach improves the sensitivity, specificity, and positive predictive value of serum markers CA 125 and OVX1. A procedure that measures complementary serum markers over time can be used as a primary screening technique followed by transvaginal ultrasonography. This could provide a cost-effective means of early detection and could significantly decrease the probability of surgical intervention for false-positive test results.

Biomarkers, Tumor↗
PubMed1995

Intraperitoneal administration of cisplatin and 5-fluorouracil in residual ovarian cancer: a Phase II Gynecologic Oncology Group trial.

Forty-eight patients with persistent or recurrent epithelial ovarian cancer who had persistent or recurrent disease following intravenous (i.v.) cisplatin-based chemotherapy were treated with intraperitoneal (ip) cisplatin and 5-fluorouracil (5-FU) as salvage therapy. All patients had surgically documented minimal residual disease (1.0 cm or less maximum tumor diameter) at the completion of surgery and were without clinical, radiographic, or histologic evidence of extraperitoneal disease. Of the 45 patients evaluable for response, 13 had a documented partial response (PR) or complete response (CR) to previously administered i.v. cisplatin (cisplatin-sensitive) while the remaining 32 patients were noted to have stable or progressive disease on the previous i.v. cisplatin regimen (cisplatin-refractory). The median number of treatment cycles was six. At the completion of eight cycles of chemotherapy, 22 patients had no clinical or radiographic evidence of persistent disease and were thus eligible for a third-look laparotomy. Seven patients refused surgical evaluation. Three of the 15 patients who underwent a third-look laparotomy had a pathologic complete response (PCR) while 3 other patients had surgically documented partial response. All the surgically documented responses were in cisplatin-sensitive patients for a surgically documented response rate in this patient population of 66.7% (3 of 9 PCR and 3 of 9 PR). The remaining nine patients, who were all previously cisplatin-refractory, had stable or progressive disease documented at third-look laparotomy. Thirty-four patients experienced leukopenia with a median WBC nadir of 2800/microliters while 12 patients experienced thrombocytopenia with the median platelet nadir of 122,000/microliters. There was one treatment-related death secondary to sepsis. Four patients experienced catheter-related complications, ip cisplatin and 5-FU as salvage therapy is feasible in a multi-institutional cooperative group trial and, in cisplatin-sensitive patients, is an effective treatment option.

Adenocarcinoma↗
PubMed1995

Assessment of dose-intensive therapy in suboptimally debulked ovarian cancer: a Gynecologic Oncology Group study.

PURPOSE: We report a prospective randomized trial in women with advanced ovarian cancer to evaluate the importance of chemotherapy dose-intensity on survival, progression-free survival (PFS), and response. PATIENTS AND METHODS: A total of 485 patients with epithelial ovarian cancer and residual masses more than 1 cm following surgery (stage III presentation) or any stage IV presentation were randomly assigned to receive either standard therapy (cyclophosphamide 500 mg/m2 and cisplatin 50 mg/m2 intravenously every 3 weeks for eight courses) or intense therapy (cyclophosphamide 1,000 mg/m2 and cisplatin 100 mg/m2 intravenously every 3 weeks for four courses). Dose modification was rigidly controlled to maintain intensity. Clinical and pathologic responses were assessed, when appropriate, as well as PFS interval and survival. RESULTS: A total of 458 patients met all eligibility criteria and were assessed for survival and PFS. The dose-intensive group received the same total dose of cyclophosphamide and cisplatin, but 1.97 times greater dose-intensity than the standard group. Clinical and pathologic response rates; response duration, and survival were similar in both groups of patients. Hematologic, gastrointestinal, febrile episodes, septic events, and renal toxicities were significantly more common and severe in the dose-intensive group. CONCLUSION: A doubling of the dose-intensity in the treatment of bulky ovarian epithelial cancers led to no discernible improvement in patient outcome and was associated with more severe toxicity. This study provides no evidence to support the hypothesis that modest increases in dose-intensity without increasing total dose are associated with significant improvement in overall survival or PFS.

Adult↗
PubMed1994

Conservative and individualized surgery for early squamous carcinoma of the vulva: the treatment of choice for stage I and II (T1-2N0-1M0) disease.

We studied the outcome of patients undergoing radical local excision (modified radical vulvectomy) with inguinal-femoral lymphadenectomy through separate groin incisions for stage I and II invasive squamous carcinoma of the vulva. The purpose was to determine whether less radical and more individualized surgery is consistent with local control and cure. We have reported previously our experience using radical local excision and modified radical vulvectomy in stage I disease (Obstet. Gynecol. 63, 155 (1984)) and with separate groin incisions (Obstet. Gynecol. 58, 574 (1981)). This current report expands our experience with stage I and adds stage II patients treated over the past decade. Seventy-four patients were studied retrospectively over the 5-year period ending in January 1990. Reviews of both patient charts and histopathology reports were correlated with recurrence and survival. Factors analyzed included FIGO stage and grade, histology, lesion size and depth of invasion, surgical procedure, radiotherapy, lymph node status, interval to and site of recurrence, and survival. Thirty-nine patients had stage I disease and 35 had stage II. The primary operation was a radical local excision (modified radical vulvectomy) in 56 patients and radical vulvectomy in 18 patients; 13 underwent ipsilateral inguinal-femoral lymphadenectomy and 58 bilateral lymphadenectomy, each through separate groin incisions. The survival of those treated conservatively (97 and 90% for stages I and II, respectively) is the same as those undergoing a radical vulvectomy (100 and 75% for stages I and II, respectively) with only the presence of inguinal-femoral lymph node metastases impacting negatively on survival. In the entire group, the survival for negative and positive nodes was 98 and 45%, respectively. In conclusion, conservative, modified, and individualized vulvectomy in both stage I and II disease is associated with the same outcome and survival as radical vulvectomy, and lymph node status is the most important prognostic factor.

Carcinoma, Squamous Cell↗
PubMed1994

Salvage therapy for recurrent and refractory ovarian cancer with high-dose chemotherapy and autologous bone marrow support: a Gynecologic Oncology Group pilot study.

Nine patients with recurrent or refractory epithelial ovarian carcinoma following previous chemotherapy were treated with high-dose carboplatin (300 mg/m2) and ifosfamide according to a dose escalation schedule (1.50, 1.75, 2.00 g/m2), each given intravenously daily for 5 days with autologous bone marrow support. Eight of the nine patients were evaluable for response. Five achieved complete response (CR), all of whom relapsed at 4, 5, 6, 8, and 23 months following treatment. Two partial responses persisted for 6 months, and one patient with stable disease progressed after 2 months and has since died of disease. The median duration of remission was 6 months. The treatment was well tolerated across the doses of ifosfamide with the exception of one treatment-related death which was due to acute renal failure and central nervous system toxicity from ifosfamide. It appears that the use of high-dose chemotherapy with autologous bone marrow support in the treatment of ovarian cancer produced a high rate of response of short duration in this small group of heavily pretreated women.

Adult↗
PubMed1994

The influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual stage III epithelial ovarian cancer after optimal primary cytoreductive surgery.

The purpose of this study was to determine the influence of tumor grade, distribution, and extent of carcinomatosis in minimal residual epithelial ovarian cancer after primary optimal cytoreductive surgery. Between 1978 and 1990, 112 patients with stage III epithelial ovarian cancer underwent primary cytoreductive surgery and had minimal residual disease, i.e., < 5 mm maximum diameter of residual tumor nodules. Seventy-eight patients (70%) had operative reports that contained sufficient detail to be included in this study. We retrospectively reviewed histopathological reports to determine tumor grade, operative and clinical notes to determine one predominant distribution pattern of residual metastases (pelvic/omental, diaphragmatic, or intestinal/mesenteric), and the approximate extent of residual disease (no gross disease, scattered nodules, or extensive carcinomatosis). Standard actuarial survival analysis was performed, and the log-rank chi 2 was used. At the mean follow-up time of 24.4 months, survival was 65% for grade 2 or 3 disease versus 93% for grade 1 (log-rank P < 0.01). Survival was 66% for residual disease in the intestines/mesentery versus 70 and 81% for residual disease in the diaphragm and pelvis/omentum, respectively (log-rank P < 0.03). Survival was 48% for residual extensive carcinomatosis versus 76 and 93% for minimal residual nodules and no gross residual, respectively (log-rank P < 0.001). In conclusion, in women who have minimal residual ovarian cancer after primary cytoreductive surgery, tumor grade and the distribution and extent of carcinomatosis can independently affect survival. The shortest survival correlated with high-grade tumor and extensive carcinomatosis predominantly involving the intestines and mesentery.

Carcinoma↗
PubMed1994

Fine-needle aspiration cytology in the management of gynecologic oncology patients.

Fine-needle aspiration cytology has received little attention by physicians involved in the care of gynecologic oncology patients. Concerns over diagnostic accuracy and complications such as rupture of cystic ovarian tumors with resultant tumor dissemination have limited the technique's utilization. Recent studies have shown the method to have a diagnostic accuracy (percent of neoplasms correctly categorized as benign or malignant) of approximately 95% for ovarian tumors [2-8]. The method is generally free of major complication when patients are properly selected, but severe pelvic infections have followed transvaginal or transrectal puncture of cystic ovarian neoplasms, resulting in a complication rate of about 1.6% [28]. Presently, FNA of ovarian tumors has a role in the workup of cystic lesions in young women where epithelial malignancies are unlikely and preservation of ovarian function is highly desirable. In peri- or postmenopausal women with adnexal masses, operative intervention is appropriate in most cases. Sevin and colleagues defined four clinical situations where FNA is useful [16]. These are 1) workup of primary neoplasms, 2) biopsy of superficial masses in patients with known prior disease, 3) follow-up of irradiated patients, and 4) follow-up of patients undergoing chemotherapy. From the available data, FNA has an accuracy of approximately 90% [10,18] and a low complication rate. The technique is an excellent method for the detection of recurrent or metastatic disease in patients being followed for gynecologic malignancies. When FNA is used for the investigation of newly discovered adnexal masses, patient selection is critical. FNA is helpful in carefully selected young women with cystic ovarian masses. However, its utility is limited in peri- or postmenopausal women with solid and solid-cystic adnexal masses, because these should be investigated by operative intervention.

Biopsy, Needle↗
PubMed1994

The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group has divided patients with advanced epithelial ovarian cancer into those with optimal residual cancer, in which the maximum diameter of residual is < or = 1 cm, and suboptimal residual cancer, in which the residual disease is > 1 cm. Within the optimal group of patients there is a survival difference between patients with microscopic residual disease and those with any macroscopic disease < or = 1 cm. No analysis of the effect of various residual disease diameters in patients with residual disease > or = 1 cm has been performed. This study evaluates the effect of residual disease diameter in patients with suboptimal disease entered on a randomized trial of intense versus standard chemotherapy. STUDY DESIGN: Gynecologic Oncology Group protocol 97 compared cisplatin 50 mg/m2 and cyclophosphamide 500 mg/m2 for eight courses with the same drugs at 100 mg/m2 and 1000 mg/m2 for four courses, respectively. There was no difference in progression-free interval or survival between the two arms. Of the 458 stage III (with residual disease > 1 cm) and stage IV patients entered in this study, 294 stage III patients comprise the current analysis. Surgical reporting forms, operation reports, and pathology reports were reviewed to determine initial greatest tumor diameter and residual tumor diameter. Patients were grouped by residual diameter. Multivariate analysis considered residual diameter of disease, age, histologic characteristics, performance status, and ascites. An adjusted relative hazard of dying of ovarian cancer was calculated for each residual disease group. RESULTS: Patients ranged in age from 20 to 80 years, with a median of 60 years. All patients were Gynecologic Oncology Group performance status 0 to 2. Fifty-two percent had grade 3 tumors, and 39% and 9%, respectively, had grade 2 or 1 tumors. All patients had stage III disease. Ninety percent had serous, endometrioid, or mixed epithelial cell type tumors. Multivariate analysis revealed a relative risk of dying as follows: residual disease < 2 cm, relative risk 1.00; 2 to 2.9 cm, relative risk 1.90; 3 to 3.9 cm, relative risk 1.91; 4 to 5.9 cm, relative risk 1.74; 6 to 7.9 cm, relative risk 1.85; 8 to 9.9 cm, relative risk 2.16; > or = 10 cm, relative risk 1.82. The difference in survival between those with < 2 cm residual disease and those with > or = 2 cm residual disease was significant (p < 0.01). There is no significant difference in the risk of dying between groups with residual disease > or = 2 cm. CONCLUSIONS: Among patients with suboptimal (> 1 cm residual disease) epithelial ovarian cancer, those who have small diameter residual disease (< 2 cm) tend to survive longer than those who have larger residual disease. Among those with larger residual disease, size does not affect prognosis appreciably.

Adult↗