Paraneoplastic cerebellar degeneration in ovarian carcinoma: case report with review of immune modulation.

Paraneoplastic cerebellar degeneration (PCD) is a rare nonmetastatic complication of a carcinoma. It is typically mediated by antibodies generated against tumor antigens. These antigens are the same proteins as expressed on Purkinje cells within the cerebellum; immune activation in the central nervous system (CNS) results in the syndrome. A 56-year-old woman with stage IIIC serous ovarian carcinoma diagnosed 3 years prior developed progressive limb ataxia. Serum anti-Yo antibodies were positive, confirming the diagnosis of PCD. Treatment with plasmaphoresis, intravenous immune globulin, and immune modulation with corticosteroids and tacrolimus was unsuccessful. Although the syndrome can be debilitating and treatment options are limited, it may also be an example of a successful host immune response in certain cases.

Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish ovarian cancer patients.

OBJECTIVE: The purpose of this study was to describe the incidence of the three Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected, consecutive group of Ashkenazi Jewish ovarian cancer patients. MATERIALS AND METHODS: From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with histologically confirmed epithelial ovarian cancer had surgery. All of these patients had DNA extracted from 5-microm sections of their paraffin-embedded surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A multiplex (triplex) polymerase chain reaction was performed to amplify fragments for the 185delAG, 5382insC, and 6174delT mutations. The products were hybridized with normal and mutant probes for each of the three mutations. All clinical data were collected retrospectively and statistical significance was evaluated using the chi(2) test or a two-tailed Fisher's exact test, depending on the sample size. RESULTS: There were 23 patients positive for one of the three founder BRCA mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients were positive for the 5382insC mutation, and 7 patients were positive for the 6174 delT mutation (61, 9, and 30%, respectively). This represented a 25% incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our 92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive for more than one mutation. There was no statistically significant difference in parity, histology, grade, or stage between the BRCA founder mutation positive and negative patients. The difference between the percentage of mutation carriers among patients with one affected first-degree relative (13/22 or 59%) compared to those without at least one affected first-degree relative (10/70 or 14%) was highly significant (P = 0.001). CONCLUSIONS: Ashkenazi Jewish ovarian cancer patients represent a group with a high likelihood of being carriers of BRCA 1 and 2 genetic mutations, regardless of family history. As a result, all ovarian cancer patients who are of Ashkenazi Jewish descent should be counseled regarding BRCA 1 and 2 genetic screening, as well as the potential implications of these results for the patient as well as her relatives in terms of prognosis, screening, chemoprevention, and consideration of prophylactic surgical procedures.

Laparoscopic lymphadenectomy for gynecologic malignancies.

OBJECTIVE: The purpose of our study was to detail our 5-year experience with laparoscopic lymphadenectomy for gynecologic malignancies. METHODS: From 11/5/92 to 3/9/98, we performed laparoscopic lymphadenectomies on 94 patients with various gynecologic malignancies. Pelvic, paraaortic, and combinations of both pelvic and paraaortic lymphadenectomies were performed depending on the primary site of disease and indication for lymph node dissection. Data were prospectively collected on all patients. RESULTS: From 11/5/92 to 3/9/98 we performed 94 laparoscopic lymphadenectomies for gynecologic malignancies. The distribution included 64 patients with cervical cancer, 14 with ovarian cancer, 12 with endometrial cancer, 2 with fallopian tube cancer, 1 with a uterine malignant mixed mesodermal tumor, and 1 with a metastatic neuroendocrine tumor. Fifty-five patients had only pelvic lymph node dissections, 9 patients had paraaortic dissections only, and 30 had both pelvic and paraaortic dissections performed. Among 30 patients having laparoscopic lymphadenectomy only, the mean hospital stay was 3.6 days. Included in this group were 19 patients who received postoperative neoadjuvant chemotherapy for cervical cancer as inpatients prior to ambulatory radiation therapy. The mean length of stay for this group was 4.6 days versus 1.7 days for the 11 patients who did not receive postoperative chemotherapy (P = 0.0025). The mean number of pelvic nodes was 11.9 (range 0-57), with a mean of 4. 5 between 11/5/92 and 12/31/95 and a mean of 19.1 from 1/1/96 to 3/9/98. The mean number of paraaortic nodes obtained was 3.7 (range 0-14), with a mean of 3.4 from 11/5/92 to 12/31/95 and a mean of 4.1 from 1/1/96 to 3/9/98. A total of 3 patients required conversions to laparotomy. One was for a vascular injury to the vena cava, 1 for a large tumor extending to both sidewalls, and the third for removal of densely matted lymph nodes. CONCLUSIONS: Laparoscopic lymphadenectomy is a technically feasible procedure for patients with gynecologic malignancies requiring lymph node dissections, with an acceptable safety profile and nodal yield. The number of nodes obtained increased in direct proportion to operator experience. In addition, patients may benefit from a decrease in hospital stay compared to conventional lymphadenectomy via laparotomy.

Laparoscopic management of adnexal masses in premenopausal and postmenopausal women.

OBJECTIVE: To evaluate the feasibility and safety of laparoscopic adnexal mass removal in patients without preselection for benign pathology and assess the operative complications and findings. METHODS: All patients presenting to the gynecologic oncology service between April 1992 and April 1996 with adnexal masses were candidates for laparoscopic management. Patients underwent preoperative radiological studies and office pelvic examination. Laparoscopic management was attempted on patients without evidence of gross metastatic disease or masses that extended above the umbilicus. Laparotomy was performed if indicated by pathologic findings or technical difficulty. All removed adnexal masses were sent for immediate pathologic diagnosis. The type of procedure, intraoperative findings, and complications were all recorded at the time of procedure. RESULTS: One hundred sixty patients underwent laparoscopic evaluation for an adnexal mass. Benign pathology was discovered in 139 (87%, 95% confidence interval [CI] 84, 90) patients, and 141 (88%, 95% CI 86, 91) patients were managed laparoscopically. Reasons for laparotomy included technical difficulty, operative complications, or malignancy. Frozen section diagnosis was concordant with the final pathology reports in all but five patients (97% concordance), and no discrepancies resulted in treatment delays. CONCLUSION: Laparoscopic management of adnexal masses can be successful in a gynecologic oncology population if there is expertise in operative laparoscopy, availability of immediate accurate pathologic examination, and appropriate further treatment where indicated.

Pelvic exenteration in gynecologic oncology: Experience at the Mount Sinai Center, 1975-1992.

Thirty-nine patients underwent pelvic exenteration for gynecologic malignancies at The Mount Sinai Medical Center between 1975 and 1992. Surgical techniques, morbidity, survival, and other variables for patients so treated in two periods, 1975-1984 and 1985-1992, were compared. The primary cancer included squamous cell carcinoma of the cervix, 27; adenocarcinoma of the cervix, 1; squamous cell carcinoma of the vagina, 4; adenocarcinoma of the endometrium, 4; squamous cell carcinoma of the vulva, 2; and adenocarcinoma of the rectum, 1. Median survival was 23.1 months, with a median follow-up of 18 months. Survival was significantly related to status of the lymph nodes (p 0.0004) and surgical margins (p 0.0038). There were two postoperative mortalities, one due to pulmonary embolus and another to myocardial infarction. The ability in the second period analyzed, 1985-1992, to integrate a continent urinary reservoir and supralevator exenteration without colostomy yet not induce increased morbidity or decreased survival, has not been previously reported.

Manchester procedure vs. vaginal hysterectomy for uterine prolapse. A comparison.

The Manchester procedure (MP) was compared with vaginal hysterectomy (VH) to determine whether any differences regarding patient demographics or operative or postoperative outcome could be found between the two techniques. A retrospective chart analysis was done comparing data from 88 consecutive MP to 105 randomly selected VH patients. All the operations were performed for uterine prolapse at Mount Sinai Hospital between 1984 and 1988. MP patients, when compared to VH patients, were more likely to be older and postmenopausal at the time of surgery and to have a private physician. MP patients were less likely to have significant medical illnesses than were VH patients. Statistically significant differences between MP and VH were found for operative time (100 vs 130 minutes, respectively) and blood loss (200 vs. 300 mL, respectively) (P < .001). This difference was not dependent on the performance of anterior or posterior repair. MP was associated with shorter operative time and less blood loss when compared to VH. This, coupled with apparently similar operative outcomes, suggests the use of MP as an alternative to VH in the absence of uterine pathology in appropriate candidates with uterine prolapse. Prospective, controlled, long-term studies comparing the operative results of these two procedures are needed.

The stapled continent ileocecal urinary reservoir in the surgical management of gynecologic malignancy.

Total cystectomy at the time of radical pelvic surgery for gynecologic malignancies is not uncommon. Many techniques have been developed for urinary diversion including the continent ileocecal urinary reservoir. Twenty-nine patients underwent construction of a continent ileocecal urinary reservoir during the reconstructive phase of an exenterative procedure or for the relief of urinary tract fistula between 1990 and 1993. All procedures were performed using the mechanical stapling devices using metal staples. The right and proximal transverse colon were mobilized to a length of 24 cm. The ileum was divided 8 cm proximal to the ileocecal valve and plicated using the stapling technique. The colonic segment was opened on its antimesenteric border and the reservoir was created by stapling in a fashion to reapproximate the distal ends to each other. The ureters were stented and implanted without tunneling. A large Malecot drain was placed in all the pouches for irrigation of the colonic mucosa in the postoperative period. The ileal stoma was fixed to the anterior abdominal wall as was the anterior surface of the pouch. Operative time ranged from 50 to 150 min for the pouch construction. All patients underwent retrograde contrast study of the pouch 7-10 days postoperatively to verify lack of anastomatic leaks. After recovery, all patients successfully self-catheterized the pouch three to five times daily without difficulty. Of the 29 patients, 17 (59%) had received prior radiation as part of therapy. All patients remained continent at the end of observation. One developed a fistula to the perineum after intraoperative placement of 125I seeds on the pelvic wall. One patient developed pouch stones; endoscopic evaluation of this pouch revealed no evidence of stones at the staple lines and metabolic workup demonstrated hypocitremia as the etiology for the stones. Mean reservoir volume was 550 ml. Mean follow-up is 15.8 months; 5 have expired due to recurrent disease and 19 (83%) remain alive. Only two patients have been admitted for urosepsis due to reflux pyelonephritis. The stapled continent ileocecal reservoir offers benefits to patients undergoing total cystectomy. Using the mechanical stapling devices decreases the operative time and has not resulted in stone formation or pouch leakage. The complications of the procedure are acceptable.

Growth factor expression in normal peritoneum of patients with gynecologic carcinoma.

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.

The application of operative laparoscopy to gynecologic oncology.

The application of operative laparoscopy to patients with gynecologic malignancy is in its infancy, but promising findings have been demonstrated for surgical end staging after cytotoxic therapy for ovarian cancer, laparoscopic lymph node sampling for cervical cancer, and laparoscopic staging, vaginal hysterectomy and adnexectomy for corpus cancer. The most significant difficulty in integrating operative laparoscopy with gynecologic oncology, at this time, is the lack of controlled studies to demonstrate the ability of endoscopy to improve the contemporary management of these diseases. Further study will be necessary by subspecialists in gynecologic oncology to demonstrate the proper application of these new techniques.

Phase II trial of etoposide, carboplatin, and ifosfamide as salvage therapy in advanced ovarian carcinoma.

A phase II study combining etoposide with carboplatin and ifosfamide as salvage therapy in advanced ovarian cancer was undertaken. Objective responses were achieved in 37.5% of 16 evaluable patients with a mean progression-free interval of 8.6 months. Stable disease was present in 25% of patients; in 37.5% of patients the disease progressed on salvage. Based on original response to front-line therapy, patients were classified as being platinum-sensitive (group I) or platinum-refractory (group II). Clinical response to salvage therapy was seen in 44.5% of group I patients, but in only 28.6% of group II patients. This difference was not statistically significant. When a more precise definition of platinum sensitivity was applied, clinical responses were seen in 54.5% of group I patients, but no responses were noted among group II patients (p < 0.05). Platinum sensitivity appeared to be an important factor in achieving a response with this regimen. This combination was well tolerated, myelotoxicity being the dose-limiting toxicity encountered. No life-threatening, nonhematologic toxicities were seen. One death occurred secondary to nadir sepsis. The combination of etoposide, carboplatin, and ifosfamide is an active salvage regimen in patients with advanced ovarian carcinoma; however, severe myelotoxicities and inability to produce long-term responses underscore the need for continued trials to find a more durable salvage regimen.

Screening for human immunodeficiency virus and sexually transmitted diseases in an inner-city colposcopy clinic.

Among patients attending an inner-city colposcopy clinic, the prevalence of Chlamydia trachomatis was 22/375 (5.0%), Neisseria gonorrhoeae, 3/375 (0.8%), and seropositivity for syphilis, 10/375 (2.7%). In addition, 13/261 (5.0%) of asymptomatic women agreeing to voluntary human immunodeficiency virus (HIV-1) antibody screening were HIV-1 seropositive. Our data support incorporating screening for and education on sexually transmitted diseases and HIV into the work of our colposcopy clinic.

Secondary cytoreduction for ovarian cancer following cisplatin therapy.

PURPOSE: This study was undertaken to evaluate the efficacy of secondary surgical cytoreduction in the management of ovarian cancer. PATIENTS AND METHODS: The cases of 100 patients with recurrent or progressive epithelial ovarian cancer whose initial treatment had been cytoreduction followed by cytotoxic therapy with a cisplatin-based regimen were reviewed. All 100 patients underwent surgery, after recurrence or progression was documented preoperatively, by gynecologic oncologists at the Mount Sinai Medical Center, New York, NY, between 1980 and 1991 with the intention of performing radical tumor reduction. RESULTS: Sixty-one patients had a secondary cytoreduction that left residual disease less than 2 cm in diameter. The median survival, determined from the date of the secondary cytoreduction to the date of death or last follow-up, is 27.1 months in the optimally treated group and 9.0 months for the 39 patients whose surgery was suboptimal (P = .0001). Other variables associated with statistically significant longer survival, and a significantly higher probability of achieving a successful secondary cytoreduction, included age < or = 55 years at the time of secondary cytoreduction, interval from initial diagnosis to secondary cytoreduction of more than 12 months, residual disease at initial staging laparotomy of less than 2 cm, and a complete clinical response to a cisplatin-based front-line regimen. Multivariate analysis confirms the survival benefit provided by a successful secondary cytoreduction when adjusted for the above variables. There was one postoperative mortality. Ten percent of the successfully cytoreduced patients and 18% of the unsuccessfully cytoreduced patients experienced some degree of postoperative morbidity. CONCLUSION: These data justify the performance of secondary cytoreductive surgery for patients who develop gross recurrent or progressive ovarian cancer following cisplatin therapy.

Feasibility of intraoperative administration of chemotherapy for gynecologic malignancies: assessment of acute postoperative morbidity.

In order to assess the acute effects of the intraoperative administration of intraperitoneal (IP) carboplatin with and without intravenous (IV) doxorubicin in patients with gynecologic malignancies, 25 patients were treated at the conclusion of their surgical procedure. Twenty-three had epithelial ovarian cancer and 2 had advanced endometrial cancer. Twelve patients received IP carboplatin and IV doxorubicin at the conclusion of their primary cytoreduction. The remaining 13 received IP carboplatin alone and consisted of 4 reassessment laparotomies for ovarian cancer, 7 secondary cytoreductions, 1 minilaparotomy for the placement of an IP catheter, and 1 second-look laparoscopy. The median age of the 25 patients was 59 years. Eight patients underwent bowel resections with anastomoses; 2 had ureteral resections and ureteroneocystostomies, 1 required a splenectomy, and 1 underwent a partial hepatic resection. There were no mortalities. Three of the 13 patients who received the IP carboplatin alone had postoperative fevers with no infectious source, which did not delay discharge. No other morbidity was noted in this group. However, 7 patients who received IV doxorubicin along with the IP carboplatin developed severe leukopenia requiring antimicrobial and colony-stimulating factor support. One patient required reexploration for postoperative hemorrhage and also developed a pulmonary embolus. One woman developed postoperative pneumonia. The median hospital stay for the 25 patients was 9 days. Intraoperative chemotherapy can be administered with tolerable immediate adverse effects.

Tamoxifen and endometrial cancer.

Tamoxifen is a nonsteroidal antiestrogen employed frequently in the treatment of breast cancer. An association between this drug and endometrial neoplasia has been reported. We report on 11 postmenopausal women with breast cancer who developed endometrial cancer while undergoing tamoxifen therapy and recommend aggressive investigation of vaginal bleeding in all women being treated with this agent.

A phase II trial of adjuvant cisplatin and doxorubicin in stage I epithelial ovarian cancer.

We have treated 26 patients with Stage I ovarian cancer with platinum-based chemotherapy. Patients received 50 mg/m2 cisplatin and 50 mg/m2 doxorubicin every 21 days for six cycles. Eighteen patients had complete surgical staging defined as total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and aortic node sampling, omentectomy, and cytology. Eight patients had all of the above with the exception of node sampling. The overall median follow-up for the group is 43+ months. Three patients had grade 1 tumors with positive washings or capsule invasion and are disease free with a median follow-up of 53+ months. Of 23 patients with grade 2-3 tumors, 22 are alive and free of disease with a median follow-up of 42+ months. There has been 1 recurrence, at 18 months, in a patient who had complete staging and a grade 2 tumor. The patient recurred with carcinomatosis, documented by laparoscopy. There was no significant hematologic, neurologic, or renal toxicity encountered in any patient. Adjuvant combination chemotherapy is beneficial for selected patients with early-stage ovarian cancer who are at high risk for failure after surgical treatment alone.

Recurrent cervical squamous cell carcinoma in an ovary following ovarian conservation and radical hysterectomy.

This is the second reported case of an ovarian recurrence of Stage I squamous cell carcinoma of the cervix. It occurs following radical hysterectomy, chemotherapy, and radiotherapy. The issue of ovarian conservation is addressed.

Induction chemotherapy followed by radical surgery in cervical cancer.

To evaluate the therapeutic potential of cytotoxic therapy in patients with squamous cell carcinoma of the cervix, 28 patients with disease clinically localized to the pelvis were treated with chemotherapy followed by radical pelvic surgery. Treatment consisted of cis-platinum 50 mg/m2, mitomycin C 10 mg/m2, vincristine 1.0 mg/m2, and bleomycin 10 U IM given as a course (over 21 days) of induction chemotherapy followed by radical hysterectomy and pelvic and aortic lymphadenectomy in 26 patients and total pelvic exenteration in 2 patients. The stage distribution of the patients in the study was 4 stage IB, 6 stage IIA, 7 stage IIB, 1 stage IIIA, 11 stage IIIB, and 1 stage IVA. Two patients with stage IIIB cancer were found, at the time of laparotomy, to have carcinomatosis and were excluded from the final evaluation in this study. All patients achieved a clinical and histologic response to chemotherapy. There were 35% complete and 65% partial responses. After chemotherapy, at the time of surgery, 4 patients were found to be histologically free of disease, and the incidence of surgically documented nodal disease after chemotherapy was found to be 32%. There was no significant hematologic or pulmonary toxicity. Induction chemotherapy is well tolerated and may be beneficial in the management of some patients with cervical cancer who are at high risk for failure with conventional treatment.