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Biomedical subjects

M L Berman

Publications and source records attributed to M L Berman.

At least 19 recordsLinked to original sources

Contracting for professional service agreements.

A review of several professional service agreements (PSA) of managed care organizations which contract with gynecologic oncologists in the Southern California area demonstrates several distinct patterns of practice restrictions and financial benefits which can help guide the physician who is considering signing such an agreement. These contracts must be evaluated in a manner similar to any business transaction as they are legally binding and can enhance or adversely impact one's clinical practice. Their advantages include increased numbers of referrals resulting in higher practice income; however, their disadvantages include practice restrictions which can adversely impact office overhead, practice efficiency, and the ability to deliver quality medical care. General guidelines to physicians evaluating a PSA include (1) avoiding "hold harmless" clauses, (2) avoiding contracts which tie enrollment in one plan to others, (3) the need to enter any verbal agreements by managed care administrators into the contract language, and (4) avoidance of actions which might be construed as being in violation of antitrust activities. Furthermore, physicians must avoid contracts which will result in the uncontrolled growth of a practice beyond its capabilities for expansion.

California

Endometrioid adenocarcinoma of the ovary and its relationship to endometriosis.

In order to better understand the clinical presentation and biologic behavior of ovarian carcinomas arising in endometriosis, we performed a historical cohort study of all women with endometrioid adenocarcinoma of the ovary (ECO) diagnosed between 1979 and 1991 at our institutions. A review of pathology reports determined the presence or absence of coexisting endometriosis. Cancers adjacent to endometriosis on the same ovary or arising within endometriosis were labeled endometriosis-associated endometrioid adenocarcinoma (EAEA), while all others were considered typical endometrioid adenocarcinoma (TEA). Associations between tumor type and clinicopathologic variables were analyzed by chi 2 and Fisher's exact tests as indicated. Disease-free interval (DFI) and overall survival were estimated using the Kaplan-Meier method. The independent prognostic significance of clinicopathologic variables was determined by multivariate analysis using the Cox proportional hazards regression model. Of 91 ECO patients identified, 63 (69%) had TEA and 28 (31%) had EAEA. Significant differences between TEA and EAEA existed for age at diagnosis (greater than 55 years; 56 vs 32%, P = 0.039), nulliparity (19 vs 46%, P = 0.007), stage (I and II combined; 37 vs 70%, P = 0.004), and disease status at completion of primary surgery (complete tumor resection; 47 vs 70%, P = 0.04). Synchronous atypical endometrial hyperplasia or uterine carcinoma was found in 7/63 (11%) TEA versus 7/28 (25%) EAEA cases (P = 0.054). Estimated 5-year DFI by life table analysis was significantly longer in the EAEA than in the TEA cohorts (57 vs 25%, P = 0.02); however, the 5-year survival difference was not significant (59 vs 45%, P = 0.18). Multivariate analysis identified only stage as an independent prognostic factor in predicting both DFI and survival. In conclusion, women with EAEA are significantly younger, present with earlier stage disease, and have a longer disease-free survival than those with TEA. These factors may reflect a more favorable biologic behavior of ECO when arising in association with endometriosis.

Adult

A phase II trial of neoadjuvant chemotherapy prior to radical hysterectomy and/or radiation therapy in the management of advanced carcinoma of the uterine cervix.

OBJECTIVE: This prospective trial was designed to access the efficacy and safety of neoadjuvant chemotherapy followed by radical hysterectomy and/or radiation therapy in women with advanced carcinoma of the uterine cervix. METHODS: Thirty women, clinical stages IIb-IVa, were enrolled in this clinical trial. Initial treatment consisted of three cycles of bleomycin, cisplatin, and vincristine administered every 10 days. Depending on the extent of disease after chemotherapy, patients then either underwent radical hysterectomy with bilateral pelvic and periaortic lymphadenectomy or surgical staging. Following review of the surgical findings, tailored radiotherapy was administered. RESULTS: Only 10 women (34%) had tumor regression from neoadjuvant chemotherapy sufficient to allow radical hysterectomy prior to tailored adjuvant radiotherapy; the remainder received primary radiotherapy after surgical staging. Two-year disease-free survival was 68, 43, and 0% for women with clinical stages II, III, and IV, respectively. Four women experienced acute toxicity from chemotherapy requiring medical intervention and eight women suffered chronic toxicities requiring hospitalization and/or surgery. CONCLUSION: The neoadjuvant chemotherapy utilized in this trial was generally ineffective in converting patients from inoperable to operable, had no apparent effect on survival, and was associated with significant toxicity.

Adult

Does perioperative blood transfusion affect survival in patients with cervical cancer treated with radical hysterectomy?

OBJECTIVE: To determine if blood transfusions during or after radical hysterectomy adversely affect survival in patients with invasive cervical carcinoma. METHODS: Two hundred eighty-three women with stage IA2-IIA cervical cancer were treated with radical hysterectomy and pelvic lymphadenectomy from 1980-1989. Thirteen were lost to follow-up, and five others received adjuvant chemotherapy. Among the remaining 265 patients, 131 were given blood transfusions during surgery or within 30 days, whereas 134 were not. The clinical and pathologic characteristics of these two groups were reviewed and analyzed statistically. RESULTS: Transfused and nontransfused patients did not differ with respect to mean age (45.0 versus 43.4 years, respectively), stage, grade, cell type, depth of invasion, or prevalence of nodal metastasis. Transfused patients more frequently received adjuvant pelvic irradiation than did nontransfused (47 versus 33%, respectively, chi 2 P < .05). After a mean follow-up of 51 months (range 13-125), 19 women (14%) in each group were diagnosed as having recurrent disease, predominantly in the pelvis. Using life-table analysis, the calculated 5-year survival was 86% for transfused and 84% for nontransfused patients, a nonsignificant difference. Disease-free survival was also similar. In the study population, grade, depth of invasion, and nodal status predicted survival. When patients were stratified according to age, cell type, stage, depth of invasion, nodal involvement, and use of adjuvant radiation, blood transfusion still did not adversely influence survival. Using the Cox proportional hazards model, only nodal status was an independent predictor of death. CONCLUSION: Perioperative blood transfusion does not impact overall survival or time to recurrence after radical hysterectomy.

Adult

Spontaneous release of interleukin-6 by primary cultures of lymphoid and tumor cell populations purified from human ovarian carcinoma.

Interleukin-6 (IL-6) is a cytokine that has been implicated as a growth factor in human ovarian carcinoma, yet the in vivo source of IL-6 in patients remains undefined. We measured IL-6 by ELISA in cell-free ascites (CFA) of 19 patients with ovarian carcinoma. IL-6 was detectable in all samples (mean level 3.3 ng/ml). To identify the cellular source of IL-6, we measured this cytokine by ELISA in 24-48 h supernatants of cultured lymphocyte-, macrophage-, and tumor cell-enriched populations purified from three solid ovarian carcinomas by centrifugal elutriation. All cell populations spontaneously released IL-6; however, tumor cells and tumor-associated macrophage released levels of IL-6 that greatly exceeded those released by tumor-associated lymphocytes. Kinetic studies revealed that IL-6 was detectable at 6 h and that levels increased in all cultures examined over a 48 h time course. These data suggest that both tumor and infiltrating host cells may be the source of the high levels of IL-6 found in carcinomatous ascites. Furthermore, although all three cell types examined may contribute to IL-6 production in patients with ovarian carcinoma, tumor cells are perhaps the most clinically significant source.

Adenocarcinoma

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

Cyclosporin enhancement of cisplatin chemotherapy in patients with refractory gynecologic cancer. A Gynecologic Oncology Group Study.

BACKGROUND: Cyclosporin has been demonstrated to reverse resistance to several antineoplastic agents including cisplatin in vitro. The purpose of this Phase I trial was to study the potential clinical application of cyclosporin modulation of cisplatin and to establish a tolerable dose of cyclosporin when combined with a standard dose of cisplatin of 75 mg/m2. METHODS: A course of therapy consisted of two cyclosporin infusions over 2 hours each, 24 hours apart, with cisplatin given 6 hours after the first dose. Treatment was repeated every 21 days. Cyclosporin was studied in a Phase I fashion at five different levels, from 1-5 mg/kg per dose. Twenty patients with refractory gynecologic cancer received 81 courses of therapy. All patients had received extensive prior chemotherapy containing cisplatin. RESULTS: Grade 4 nephrotoxicity was seen in 4 of 20 patients: 1 treated at 1 mg/kg, 1 at 2 mg/kg, and 2 at 5 mg/kg of cyclosporin. The patient treated at the 1 mg/kg level was a partial clinical responder and tolerated six courses. The patient at the 2 mg/kg level had received 14 prior courses of cisplatin and tolerated only two additional courses before a Grade 4 renal toxicity developed. Grade 4 nephrotoxicity developed in the two patients receiving 5 mg after two courses of chemotherapy. Two of the 20 patients achieved a complete response (CR) and 3 patients achieved a partial response (PR), for a total response rate of 25% (5 of 20). The two women who achieved CR started treatment with symptomatic ascites; one of whom also had multiple pulmonary lesions that were no longer evident after three courses of therapy. CONCLUSIONS: Cyclosporin at a dose of 4 mg/kg per day given for 2 consecutive days in association with 75 mg/m2 of cisplatin can be given with reasonable assurance of safety.

Antineoplastic Combined Chemotherapy Protocols

Extent of disease as an indication for pelvic radiation following radical hysterectomy and bilateral pelvic lymph node dissection in the treatment of stage IB and IIA cervical carcinoma.

The role of adjuvant pelvic radiation following radical hysterectomy and pelvic lymph node dissection in the treatment of stage IB and IIA cervical cancer is controversial. Patients most likely to benefit from postoperative radiation include those with lesions that invade deeply into the cervical stroma, extend into the parametria, or have metastasized to regional lymph nodes. Between 1977 and 1987, 95 patients were treated with this combined regimen at the University of California Irvine Medical Center and Long Beach Memorial Medical Center, including 30 patients with deep cervical stromal invasion alone, 9 patients with parametrial extension alone, 37 patients with lymph node metastasis alone, and 19 patients with both positive nodes and parametrial extension. The estimated 5-year survival for this high-risk population was 67%. Pelvic recurrences alone occurred in 12 (13%) patients, and 14 additional patients (15%) recurred outside of the radiation field. In the node-positive group, the 5-year survival was 78% when the parametrium was not involved but decreased to 39% when parametrial extension was documented (P < 0.05). Patients with grossly involved nodes or multiple nodal metastases were also more likely to recur. Finally, the estimated 5-year survival for patients with deep cervical stromal invasion as the sole indication for radiotherapy was 73%. A retrospective analysis identified tumor grade and cell type also to be of prognostic importance. Severe complications attributable to radiation combined with radical surgery included two small bowel obstructions and one urinary tract fistula. These data suggest that radical hysterectomy, pelvic lymphadenectomy, and adjuvant radiotherapy produce favorable survival results with limited morbidity in patients with high-risk cervical cancer independent of node status except in that subset of patients with both occult parametrial spread and nodal metastasis.

Adult

Primary vaginal melanoma: improved survival with radical pelvic surgery.

Primary vaginal melanoma is an aggressive and rare gynecological malignancy with < 150 reported cases to date. Historically, patients with this disease have a poor prognosis for all types of treatment. In several studies containing small numbers of patients conservative therapy often has been recommended. Eight patients from our institute with this disease were divided into two groups according to therapy: Group A, radical (4); and Group B, conservative (4). The groups were compared for stage, age, surface area of the lesion, and quality of life. The 2-year survival in Group A (75%) was significantly better than that of group B (0%). There was also found to be an improved survival in patients who had lesions with a surface area < 10 cm2. Age and stage of disease did not affect prognosis. Quality of life was not reduced in the radical group. A review of all reported cases since 1949 (119) was then performed. These were divided into the same Group A, radical (50); and Group B, conservative (69). Again, a statistically significant improved outcome was found with the radically treated patients (48%) when compared to the conservatively treated patients (20%). Our findings suggest that radical surgery for patients with primary vaginal melanoma is recommended in patients with lesions < 10 cm2.

Adult

Adhesions after extensive gynecologic surgery: clinical significance, etiology, and prevention.

Postoperative adhesions occur in 60% to 90% of patients undergoing major gynecologic surgery and represent one of the most common causes of intestinal obstruction in the industrialized world. The incidence of adhesion-related intestinal obstruction after gynecologic surgery for benign conditions without hysterectomy is approximately 0.3%, increasing to 2% to 3% among patients who undergo hysterectomy, and is as high as 5% if a radical hysterectomy is performed. Other adhesion-related complications include chronic pelvic pain, ureteral obstruction, and voiding dysfunction. Intraperitoneal adhesions also can limit the effectiveness of intraperitoneal therapeutic agents used in cancer treatment. Postoperative adhesions are sequelae of impaired fibrinolysis of the fibrin and cellular exudate after peritoneal injury. Adequate blood supply is essential for normal fibrinolysis. Therefore factors that increase ischemia and potentiate adhesion formation include thermal injury, infection, presence of a foreign body, and radiation-induced endarteritis. Only recently, appropriate animal models have been developed to study the process of adhesion formation and prevention. Until clinical confirmation of findings from these investigations exists, only a meticulous surgical technique can be advocated to minimize these untoward effects of surgery.

Animals

Comparison of the polymerase chain reaction and Southern blot analysis in detecting and typing human papilloma virus deoxyribonucleic acid in tumors of the lower female genital tract.

To conduct studies on the clinical and pathologic significance of human papilloma virus (HPV) in genital malignancies, accurate detection and typing of the virus in clinical material are essential. Currently, Southern blotting and the polymerase chain reaction (PCR) are two of the most commonly used methods to identify HPV. This study was undertaken to compare these techniques in the detection and typing of HPV in 242 invasive malignancies of the lower female genital tract. BamHI and PstI restriction digests of tumor DNA were hybridized to 32P-labeled probes for HPV types 6, 16, and 18 at TM -20 degrees C after Southern transfer. Blots were then washed at Tm -20 degrees C and Tm -9 degrees C. The DNA was also amplified by PCR using both highly conserved consensus L1 primers that detect 25 different HPV genotypes and primers specific for HPV 6 E6, 16 E7, and 18 E6. All PCR products were hybridized to type-specific radiolabeled probes. In 202 of the 242 (83%) samples, HPV was detected, including 189 of 218 (87%) cervical cancers, 11 of the 20 (55%) vulvar cancers, and two of four tumors from the vagina, urethra, or anus. In 67% of the specimens, there was agreement between the Southern blot technique and both methods of PCR (consensus and type-specific primers), including 121 of the 202 HPV-positive specimens and 40 HPV-negative specimens. Of the 141 tumors with HPV detected by Southern blot analysis, the same HPV type was detected by PCR in 121 (86%).(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence

Cost analysis of Hickman catheter insertion at bedside in gynecologic oncology patients.

BACKGROUND: Cost-containment issues are becoming increasingly important in medicine. The current study compares bedside versus operating room insertion of Hickman catheters from a cost and safety standpoint. STUDY DESIGN: A prospective chart review of all patients undergoing Hickman catheter insertion during the study period was performed to determine location of the procedure, rate of successful catheter placement, complications, and cost. RESULTS: Ninety-six patients underwent placement of 108 Hickman catheters during a seven year period. Fifty-three catheters were inserted at bedside while 55 catheters were placed in the operating room. The complication rate was 8 percent for the bedside and 9 percent for the operating room group. Due to anesthesia standby, operating room time, and fluoroscopy, cost analysis revealed a substantial savings of $1,545 per patient if bedside insertion was utilized. CONCLUSIONS: The data indicate that, in select patients, percutaneous insertion of Hickman catheters at bedside is a safe, cost-effective procedure.

Catheterization, Central Venous

A new method of continuous vaginal cuff closure at abdominal hysterectomy.

A new method for vaginal cuff closure at abdominal hysterectomy avoids blood loss and spillage of vaginal contents into the peritoneal cavity. Using two separate running and interlocking absorbable monofilament sutures, the technique keeps the vagina closed at all times and avoids damage to the bladder or ureters. In 77 consecutive patients undergoing abdominal hysterectomy for endometrial cancer, morbidity related to the cuff closure included cuff cellulitis in only 2.6%, granulation tissue in 3.1%, and postoperative bleeding in none of the patients.

Blood Loss, Surgical

Identification of the MN antigen as a diagnostic biomarker of cervical intraepithelial squamous and glandular neoplasia and cervical carcinomas.

A new tumor-associated antigen, MN, has been identified whose expression correlates with the tumorigenic phenotype of HeLa x fibroblast somatic cell hybrids. Because HeLa is a cell line derived from a cervical carcinoma, we investigated the diagnostic utility of MN expression in cervical neoplasia. It was found that normal cervical tissue does not express the antigen, or does so in occasional focal areas of weakly staining reserve cells. In contrast, significant immunoreactivity (immunoperoxidase staining of paraffin-embedded sections) was observed in cervical intraepithelial neoplasias, adenocarcinoma in situ, and frank carcinomas, both squamous cell and adenocarcinoma. Varying patterns of immunoreactivity were observed and were characterized as diffuse, diffuse/focal, or focal. Greater than 90% of dysplastic or malignant tissues showed immunoreactivity. An interesting observation was that normal cervical tissue associated with cervical intraepithelial neoplasias, or adenocarcinoma in situ showed a staining pattern in the reserve cells and/or normal columnar cells that approximated the level of intensity exhibited by the dysplastic tissue. These results indicate that MN antigen expression has potential utility as a biomarker of cervical neoplasms.

Adenocarcinoma

To drain or not to drain: a retrospective study of closed-suction drainage following radical hysterectomy with pelvic lymphadenectomy.

The records of 115 patients were reviewed following radical hysterectomy with pelvic lymphadenectomy for early stage (IA2 to IIB) cervical cancer to determine the effectiveness of closed-suction drainage in decreasing postoperative morbidity. In Group 1 (n = 67), closed-suction (Jackson-Pratt) drains were placed bilaterally in the pelvic lymphadenectomy sites, whereas in Group 2 (n = 48), no drains were utilized. The groups were similar for mean age, tumor histology, disease stage, and preoperative serum albumin and total protein. There was no difference in the mean operative time, mean estimated blood loss, or transfusion rate. Likewise, febrile morbidity rates, incidence of pelvic cellulitis, length of postoperative ileus, and total hospital stay were similar. Group 1 had an increased rate of rehospitalization and morbidity directly related to the presence of the drains. The data suggest that prophylactic surgical drainage may not be necessary to prevent postoperative morbidity following radical hysterectomy with pelvic lymphadenectomy and on occasion contributes to postoperative complications.

Adult

Moderate alcohol consumption and the risk of endometrial cancer.

In a multicenter case-control study that included 400 cases and 297 controls, we examined the relation of moderate alcohol consumption to risk of endometrial cancer. We estimated average weekly intake of alcohol during adulthood from the reported frequency of intake of beer, wine, and liquor. The relative risk of endometrial cancer was 0.82 (95% confidence interval = 0.6-1.2) among women who drank, compared with lifelong abstainers. The weak protective effect of alcohol was due to a stronger inverse association among young women (< 55 years). In young women, the age-adjusted relative risks for three levels of drinking ( < 1, 1-4, > 4 drinks per week), from lowest to highest, were 0.78, 0.64, and 0.41 compared with nondrinkers. The risk estimates were not materially altered after adjustment for a variety of factors related to alcohol intake and to low risk of the disease (for example, smoking, oral contraceptive use, low body mass index, increased physical activity). The protective effect of alcohol could not be attributed to one particular type of alcohol-containing beverage, but beer appeared to have the most pronounced effect. These results suggest an inverse association between moderate alcohol consumption and endometrial cancer risk among young women, but support for a causal association is qualified and requires confirmation.

Adult

Domain structure of human 72-kDa gelatinase/type IV collagenase. Characterization of proteolytic activity and identification of the tissue inhibitor of metalloproteinase-2 (TIMP-2) binding regions.

The 72-kDa gelatinase/type IV collagenase, a metalloproteinase thought to play a role in metastasis and in angiogenesis, forms a noncovalent stoichiometric complex with the tissue inhibitor of metalloproteinase-2 (TIMP-2), a potent inhibitor of enzyme activity. To define the regions of the 72-kDa gelatinase responsible for TIMP-2 binding, a series of NH2- and COOH-terminal deletions of the enzyme were constructed using the polymerase chain reaction technique. The full-length and the truncated enzymes were expressed in a recombinant vaccinia virus mammalian cell expression system (Vac/T7). Two truncated enzymes ending at residues 425 (delta 426-631) and 454 (delta 455-631) were purified. Like the full-length recombinant 72-kDa gelatinase, both COOH-terminally truncated enzymes were activated with organomercurial and digested gelatin and native collagen type IV. In contrast to the full-length enzyme, delta 426-631 and delta 455-631 enzymes were less sensitive to TIMP-2 inhibition requiring 10 mol of TIMP-2/mol of enzyme to achieve maximal inhibition of enzymatic activity. The activated but not the latent forms of the delta 426-631 and delta 455-631 proteins formed a complex with TIMP-2 only when excess molar concentrations of inhibitor were used. We also expressed the 205-amino acid COOH-terminal fragment, delta 1-426, and found that it binds TIMP-2. In addition, a truncated version of the 72-kDa gelatinase lacking the NH2-terminal 78 amino acids (delta 1-78) of the proenzyme retained the ability to bind TIMP-2. These studies demonstrate that 72-kDa gelatinases lacking the COOH-terminal domain retain full enzymatic activity but acquire a reduced sensitivity to TIMP-2 inhibition. These data suggest that both the active site and the COOH-terminal tail of the 72-kDa gelatinase independently and cooperatively participate in TIMP-2 binding.

Base Sequence