Upper abdominal cytoreduction and thoracoscopy for advanced epithelial ovarian cancer: unanswered questions and the impact on treatment.

Gynaecological oncologists, by conducting Phase II and III chemotherapy trials, have sought to improve survival in women with epithelial ovarian cancer. The greatest impact on survival has been the use of intraperitoneal chemotherapy in women who have had all visible disease removed. No change in drug regimen has had an impact on survival equivalent to that associated with complete cytoreduction or the use of intraperitoneal chemotherapy. Interestingly, these two treatment modalities (complete cytoreduction and intraperitoneal chemotherapy) have not been universally adopted. Most often it is the inability to achieve optimal cytoreduction in the upper abdomen that defines the limit of the cytoreductive effort, and ultimately the integration of intraperitoneal chemotherapy. The importance of identifying disease outside the abdominal cavity, along with achieving complete cytoreduction, is paramount, if the use of intraperitoneal chemotherapy is to be logically integrated in treatment algorithms for women with advanced-stage epithelial ovarian cancer. This report summarises pertinent literature on upper abdominal cytoreduction, discusses surgical techniques and introduces new data on women with epithelial ovarian cancer undergoing thoracoscopy, suggesting consideration of its incorporation into the surgical management of advanced epithelial ovarian cancer.

Carbonic anhydrase IX (CA-IX) and high-risk human papillomavirus (H-HPV) as diagnostic biomarkers of cervical dysplasia/neoplasia in Japanese women with a cytologic diagnosis of atypical glandular cells (AGC): a Gynecologic Oncology Group (GOG) Study.

BACKGROUND: High-risk human papillomavirus (H-HPV) infection is linked to cervical neoplasia but its role in detecting cervical glandular lesions (GLs) is unclear. Carbonic anhydrase IX (CA-IX) is a hypoxic biomarker that is highly expressed in neoplastic cervical GLs. The diagnostic utility of these biomarkers was evaluated by the Gynecologic Oncology Group in Japanese women with a cytological diagnosis of atypical glandular cells. METHODS: Immunostaining was used to detect CA-IX in a conventional Pap smear. Immunoreactivity of CA-IX was interpreted by a panel of pathologists blinded to the histological diagnosis. Polymerase chain reaction was used to detect H-HPV in a liquid-based cytology specimen. RESULTS: Significant cervical lesions (SCLs), defined as cervical intraepithelial neoplasia (CIN2, CIN3), adenocarcinoma in situ or invasive carcinoma, were observed in 37/88 (42%) of women. CA-IX testing alone (n=88) had a sensitivity of 89, 100 or 73% for SCLs, GLs or significant squamous lesions (SLs), respectively, with a false negative rate (FNR) of 14%. Testing for H-HPV (n=84) had a sensitivity of 65, 53 or 80% for SCLs, GLs or SLs, respectively, with a FNR of 22%. The combination of CA-IX and H-HPV testing had a sensitivity of 97, 100 or 93% for SCLs, GLs or SLs, respectively, with a FNR of 5%. Among eight H-HPV-negative GLs, six (75%) had a diagnosis of lobular endocervical glandular hyperplasia (LEGH). CONCLUSION: The combination of CA-IX and HPV testing improved the diagnostic accuracy. The low rate of H-HPV positivity in the GLs was associated with coexisting LEGH independent of H-HPV.

Tumor heterogeneity in ovarian cancer as demonstrated by in vitro chemoresistance assays.

OBJECTIVE: Tumor heterogeneity has been demonstrated in solid tumors. In vitro assays were developed in an effort to predict in vivo tumor response to therapy. We compare the in vitro assay results from multiple synchronous tumor samples in primary and recurrent ovarian cancers. METHODS: 38 patients underwent surgery for primary (18) or recurrent (20) ovarian cancer. Two (22) or three (16) samples were obtained per patient and tested using the EDR assay (Oncotech, Inc.). The percentage of Extreme (E), Intermediate (I) and Low (L) drug resistance for each chemotherapy was compared between synchronous specimens. RESULTS: A total of 92 samples were collected and 787 drug assays were performed. Tumor heterogeneity was seen in 22.4% of all cases, including 18.6% primary and 26.1% recurrent diseases (p=0.01). Two category differences (L vs. E) were seen in 4.1% primary and 11.3% recurrent cases (7.8% of all cases). Overall, an increased frequency in EDR was seen in recurrent disease as compared to primary for all agents tested (22.9% primary vs. 31.6% recurrent, p=0.006). Marked heterogeneity of the drug resistance profiles was seen with paclitaxel as compared with cisplatin/gemcitabine (p=0.03), taxotere (p=0.04) or topotecan (p=0.04). No association was demonstrated between assay results and clinicopathologic parameters collected in this cohort. CONCLUSIONS: Treatment failure is often attributed to the development of chemoresistance. These results suggest that tumor heterogeneity may play an equally important role in treatment failure. Recurrent lesions exhibit greater heterogeneity and more frequent EDR. These data can influence therapeutic strategy i.e., multiple samples, sequential, or consolidation therapy.

Phase II trial of intraperitoneal paclitaxel in carcinoma of the ovary, tube, and peritoneum: a Gynecologic Oncology Group Study.

PURPOSE: To determine the response rate of intraperitoneal (i.p.) paclitaxel in patients with small-volume residual carcinomas of the ovary, fallopian tube, or peritoneum. PATIENTS AND METHODS: Eligibility criteria included patients with one of the cancers noted above, with the largest residual disease 0.5 cm or less in maximum diameter at the end of second-look surgery, and prior treatment with systemic paclitaxel was permitted. The treatment plan was paclitaxel 60 mg/m2 i.p. weekly for 16 weeks, followed by surgical evaluation in patients without evidence of disease progression. RESULTS: Of 80 patients entered onto the study, 76 were eligible, of whom 86% were considered to be potentially cisplatin-sensitive. Although five patients (7%) did not complete the first course of therapy because of catheter leakage or blockade, 53 patients (70%) received all 16 planned courses. Only 14 patients (18%) received fewer than 11 courses. Treatment was well tolerated, which included only moderate abdominal pain (grade 2, 12 patients; grade 3, one patient) and minimal neutropenia (grade 2, three patients; grade 3, one patient). Of 28 assessable patients with microscopic disease at the start of i.p. therapy, 17 patients (61%) achieved a surgically defined complete response (CR). Only one of 31 patients (3%) with any macroscopic disease achieved a CR. Of the eligible patients, 18 of 76 (24%) achieved a CR. CONCLUSION: Salvage i.p. paclitaxel is tolerable and active in patients with microscopic residual disease. The impact of this treatment strategy on survival remains to be assessed in a phase III trial.

Whole abdominal radiotherapy versus combination chemotherapy with doxorubicin and cisplatin in advanced endometrial carcinoma (phase III): Gynecologic Oncology Group Study No. 122.

Although localized endometrial cancer is effectively treated with surgery and radiation therapy, the treatment of advanced disease remains problematic. With increasing utilization of primary surgical staging and therapy, the early identification of patients with tumor spread beyond the uterus is becoming routine. The impact of adjuvant radiotherapy and/or chemotherapy in these patients remains to be demonstrated. In several institutions, whole abdominal radiation therapy has been used with some success as adjuvant treatment in selected patients with advanced disease. The Gynecologic Oncology Group (GOG) has completed a phase II trial of the whole abdominal radiotherapy in this patient population. Although data analysis is not complete, the regimen employed appears to be tolerable and shows some evidence of efficacy. In previous GOG trials, cisplatin and doxorubicin have shown single-agent activity in patients with measurable, advanced endometrial cancer. Subsequently, the response rate with the combination of cisplatin and doxorubicin was found to be superior to that with doxorubicin alone. Because approximately 30%-50% of patients with extrauterine disease have systemic failure, the evaluation of combination chemotherapy with doxorubicin and cisplatin in the adjuvant setting seemed warranted. The current ongoing prospective, randomized trial (GOG No. 122) compares the survival and the progression-free interval and treatment failure patterns in patients with endometrial carcinoma of stage III or IV with up to 2 cm of residual disease when treated with either whole abdominal radiotherapy or a combination of doxorubicin and cisplatin. The incidence and type of acute and late adverse events observed with the two treatment regimens were determined and compared.

Chemotherapy, early surgical reassessment, and hyperfractionated abdominal radiotherapy in stage III ovarian cancer: results of a gynecologic oncology group study.

PURPOSE: To determine outcomes and treatment toxicities in patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma treated with three courses of cisplatin-cyclophosphamide, surgical reassessment (SRA), and hyperfractionated whole abdominal irradiation (WAI). METHODS AND MATERIALS: Forty-two eligible patients entered this prospective Phase II study conducted by the Gynecologic Oncology Group (GOG). Disease characteristics were as follows: age range, 32-76 years (median 58); Stage IIIA (n = 1, 2%), IIIB (n = 2, 5%), IIIC (n = 39, 93%); histology-serous papillary (n = 21, 50%); other (n = 21, 50%); Grade 1 (n = 1, 2%); 2 (n = 14, 33%); 3 (n = 27, 54%); residual disease after initial surgery (present: n = 23, 55%; absent: n = 19, 45%). Five patients progressed while on chemotherapy, could not be effectively cytoreduced, and were not eligible for WAI. Of the remaining 37 patients, 35 received WAI. Surgical reassessment was not performed in five patients. RESULTS: Of 37 patients with known SRA status after chemotherapy, 21 (57%) were grossly positive, 4 (11%) were microscopically positive, and 12 (32%) were negative. Based on measurements recorded following initial laparotomy and surgical reassessment, progression during chemotherapy was noted in 40%, stage disease in 37%, and objective response in 23%. Toxicity during hyperfractionated WAI was limited and reversible. No patient beginning WAI failed to complete or required a significant treatment break. Following WAI, six patients underwent laparotomies for abdominal symptoms; five had recurrent disease. Five additional patients were managed conservatively for small bowel obstruction (SBO) or malabsorption, of whom three subsequently developed recurrence. Twenty-two patients having pelvic boosts were significantly more likely to require management for gastrointestinal morbidity (p = 0.0021). Considering all eligible patients, median disease-free and overall survivals were 18.5 and 39 months, respectively. Considering patients completing chemotherapy and WAI, median disease-free and overall survivals were 24 and 46 months, respectively. CONCLUSIONS: (a) Disease progression occurred within three cycles of cisplatin and cyclophosphamide chemotherapy in 40% of patients with optimal (< or = 1 cm residual) Stage III ovarian carcinoma. (b) Following limited chemotherapy, hyper-fractionated WAI was acutely well tolerated. (c) Late radiation-related toxicity was observed in only three patients (8.6%) in the absence of recurrent disease. Late gastrointestinal morbidity was significantly associated with the administration of a pelvic radiotherapy (RT) boost. (d) Short duration chemotherapy followed by SRA and hyperfractionated WAI without a pelvic boost is a promising management option for patients with optimal Stage III ovarian cancer. A Phase III trial will be necessary to determine how this treatment strategy compares with chemotherapy or RT alone in this patient population.

Laparoscopic staging of the patient with incompletely staged early adenocarcinoma of the endometrium.

OBJECTIVE: To determine the feasibility of laparoscopic staging in patients with presumed early stage but incompletely surgically staged adenocarcinoma of the endometrium. METHODS: Thirteen patients with incompletely staged adenocarcinoma of the endometrium underwent laparoscopic staging. The women ranged in age from 36-74 years (mean age 64) and weighed 132-201 lb (mean 147.5). The interval between hysterectomy and laparoscopic staging ranged from 14-63 days, for an average of 47. All patients underwent inspection of the entire intraperitoneal cavity, procurement of pelvic washings, and/or pelvic or para-aortic lymphadenectomy, and two patients had remaining ovaries removed. RESULTS: Extrauterine disease was found in three patients: One had intraperitoneal washings positive for adenocarcinoma, and two had pelvic lymph nodes positive for microscopic carcinoma. The average number of lymph nodes removed was 17.5. There were no intraoperative complications. Estimated blood loss averaged less than 50 mL, and the mean hospital stay was 1.5 days. CONCLUSION: Our initial experience indicates that this is a safe, effective procedure that offers a short hospital stay. We consider laparoscopic staging an attractive option for some patients with incompletely staged early adenocarcinoma of the endometrium.

Resumption of ovulation after ectopic pregnancy.

Forty-four patients with ectopic pregnancies were followed with serial serum progesterone determinations for up to 40 days after surgery. Seven patients (16%) failed to show luteal function during the study. Thirty-seven (84%) demonstrated luteal activity (serum progesterone at least 3 ng/mL): in six patients by days 17-19, in 50% by day 24, and in 72% by day 30. Because hormonal contraception delayed until the first postoperative office visit would miss the onset of folliculogenesis in approximately three-quarters of ectopic pregnancies, contraception should be begun immediately after surgery.

Sarcoid-like lesions associated with epithelial ovarian adenocarcinoma.

A woman with poorly differentiated endometrioid adenocarcinoma of the ovary had sarcoid-like lesions in the bone marrow. Sarcoid-like lesions may be misinterpreted as metastatic disease, resulting in inappropriate modification of therapy.

A critical evaluation of the endocervical curettage.

A prospective study was undertaken to critically evaluate the endocervical curettage. The study group consisted of 261 patients with colposcopically identifiable cervical lesions that had not been previously biopsied and were not macroscopically suspicious for invasive cancer. In 210 patients, the entire lesion, transformation zone, and squamocolumnar junction were visible (satisfactory colposcopy), and in 51 patients, the full extent of the lesion was not visualized colposcopically (unsatisfactory colposcopy). We used a method of examination not previously described. Colposcopy was performed before and after the endocervical curettage, but before the ectocervical biopsy. This method of examination allowed us to identify potentially contaminated endocervical curettages and to test the null hypothesis that a positive endocervical curettage in patients with satisfactory colposcopy is not the result of contamination. Twenty of 210 endocervical curettages in patients with satisfactory colposcopy were potentially contaminated, as suggested by an ectocervical lesion disrupted by the endocervical curettage. No patient with a positive endocervical curettage had an intact ectocervical lesion. Therefore, the null hypothesis was rejected (P less than .005). Of the 51 patients with unsatisfactory colposcopy, 39 (76%) underwent cone biopsy. Invasive cancer was diagnosed by cone biopsy in two patients when both ectocervical biopsy and endocervical curettage demonstrated only dysplasia. We also confirmed that patients with unsatisfactory colposcopy occasionally benefit from having an endocervical curettage. However, basing the treatment plan for any lesion short of invasive cancer solely on the results of colposcopy, ectocervical biopsy, and/or endocervical curettage could lead to significant undertreatment of some patients.

The clinical significance of blood transfusion at the time of radical hysterectomy.

A retrospective review was conducted to evaluate the clinical implications of perioperative blood transfusion in the surgical management of stage IB cervical cancer. The investigation focused on 126 patients treated with radical hysterectomy and retroperitoneal lymph node dissection who were found to have clear surgical margins, negative retroperitoneal lymph nodes, and no lymph-vascular space involvement in the hysterectomy specimen, and who had no perioperative radiation therapy, no history of immunosuppression with medication, and at least 18 months of follow-up. The distributions of age, weight, operative time, nodal yields, mean lesion diameters, median depths of invasion, and histologic subtypes were not statistically different between the transfused and untransfused groups. The average estimated blood loss among the transfused patients was 1104 mL, compared with 764 mL among the untransfused patients (P = .015). Among the 68 who received blood perioperatively, there were ten recurrences (14.7%), compared with two (3.4%) among the 58 patients who did not receive blood (P = .035). In this select population of patients, in which perioperative transfusion was isolated as a variable, transfusion adversely affected the outcome of surgical therapy.

Lithokelyphos. A case report and literature review.

Retained abdominal pregnancy is an extremely rare complication of pregnancy. A patient presented with an intraabdominal pregnancy that had been retained for 29 years.

Efficacy and safety of single-dose ceftizoxime vs. multiple-dose cefoxitin in preventing infection after vaginal hysterectomy.

The efficacy, safety and effect of a single, 1-g dose of ceftizoxime on the return of vaginal flora were compared to those of the standard regimen of three 2-g doses of cefoxitin for prophylaxis in 99 randomized women undergoing vaginal hysterectomy. Thirty-four were studied in Dallas and 65 in Los Angeles. Surgical procedures were comparable for all the antibiotic groups, although proportionately more simple hysterectomies were performed in Dallas. The patients received a povidone-iodine vaginal preparation immediately before surgery; vaginal packs, when used, contained no antimicrobial agents. Primary prophylactic failure (operative site infection) occurred in 1 of 52 (1.9%) and 4 of 47 (8.5%) of the ceftizoxime- and cefoxitin-treated patients, respectively, for a nonsignificant difference. All five primary prophylactic failures occurred in the Los Angeles patients. One patient in each antibiotic group developed a urinary tract infection and was classified as a secondary prophylactic failure. Febrile morbidity, length of hospital stay and incidence of adverse effects did not differ by antibiotic. The enterococcus was commonly found in the postoperative vaginal flora and was of no value in predicting operative-site infection. Enterobacter species and Pseudomonas aeruginosa were isolated more commonly in patients who received cefoxitin. Diphtheroids, Staphylococcus epidermidis and Peptostreptococcus species were isolated more commonly in patients treated with ceftizoxime.(ABSTRACT TRUNCATED AT 250 WORDS)

The relative importance of surgical training and laboratory research in a gynecologic oncology fellowship.

The objective was to determine trends of surgical skill acquisition during fellowships, and the consensus amongst gynecologic oncologists about the relative importance of surgical training and laboratory research in fellowships. A survey addressing surgical capability at the time of fellowship completion, and relative priorities that should be given to surgical training and laboratory research was mailed to gynecologic oncologists and fellows in the Society of Gynecologic Oncologists directory. Of 820 surveyed, 454 (55.4%) of provided utilizable data, of whom 56 (12.5%) were fellows, and 398 (87.5%) in practice (49.5% university-based and 50.5% community hospital-based). Relative to past graduates, recent ones report and current fellows anticipate a lower probability of being able to independently perform some procedures applicable to cervical and ovarian cancer, as well as others necessary to manage complications at the time of fellowship completion. 69.8% of all respondents think that greater emphasis should be placed on surgical training at the expense of doing less laboratory research. There is wide variation of opinion among respondents concerning the value of and most appropriate length of time that should be dedicated to laboratory research in a fellowship. There is an indication of a trend for more recent fellows to graduate having acquired less surgical skill and a prevalent opinion that surgical training should be more heavily emphasized in fellowships.

The use of vascular clips to minimize blood loss in colpourethropexy.

A serious intraoperative and postoperative complication associated with colpourethropexy as described by Burch and Tanagho and others is hemorrhage. We performed the Tanagho modification of the Burch procedure in 13 patients, as the sole procedure in the treatment of genuine stress incontinence. Vascular clips were used to circumscribe the fat overlying the anterior part of the vaginal wall, thereby allowing en bloc resection of the vascular fat pad. Suspensory sutures of 1-0 Vicryl (polyglactin 910) were placed; no retroperitoneal drains were used. The blood loss was estimated to be less than 50 milliliters in ten instances and less than 75 milliliters in three. The average hospital stay was 4.2 days. All of the patients were given antibiotic prophylaxis and were discharged home with suprapubic drainage of the bladder. There were no intraoperative or postoperative complications. Thus, one of the serious complications of colpourethropexy can be avoided by using vascular clips to facilitate the removal of the periurethral and paravesical fat from the anterior part of the vaginal wall.

Needle catheter jejunostomy: a controlled, prospective, randomized trial in patients with gynecologic malignancy.

Sixty patients with gynecologic cancer entered a prospective, randomized study of immediate postoperative feeding. Thirty-three women in the study group received an elemental diet (Vivonex HN) delivered through a needle catheter jejunostomy. Twenty-seven patients in the control group were given standard 5% dextrose and electrolyte solutions. Patients in both groups were stratified according to nutritional status as determined by anthropometric evaluation and levels of serum albumin, total protein, and transferrin. These parameters also were measured at intervals throughout the study. Only one catheter-related complication occurred. Patients in the study group received significantly more calories (p = 0.01) and were better able to maintain serum levels of transferrin (p = 0.05) than those in the control group. An elemental diet administered through the needle catheter jejunostomy effectively maintains postoperative nutrition and is associated with few complications.