Second-look laparotomy after modified posterior exenteration: patterns of persistence and recurrence in patients with stage III and stage IV ovarian cancer.

OBJECTIVE: The purpose of this study was to determine patterns of persistence and recurrence in patients with advanced ovarian cancer (stage IIIC and stage IV) after modified posterior exenteration. STUDY DESIGN: Retrospective chart review was used to determine patterns of persistence and recurrence of disease in patients undergoing modified posterior exenteration. From January 1, 1987, to September 15, 1998, 151 of 212 (71.2%) patients undergoing modified posterior exenteration in addition to other cytoreductive surgical procedures for stage IIIC and stage IV ovarian cancer underwent second-look laparotomy. The average age of the patients was 60.3 years (range, 20.3-86.3). A total of 207 of the 212 (97.6%) had grade 2 or 3 disease. Papillary serous carcinoma (113/212; 53.3%) and adenocarcinoma (75/212; 35.4%) were the most frequent cell types encountered. After initial cytoreductive surgery, minimal disease (<5 mm) was present in 206 of the 212 (96.2%) patients with 153 of 212 (72.2%) having no visible residual disease. There were 4 (1.9%) postoperative deaths. In 13 patients (6.1%) progressive disease was noted. Second-look laparotomy was not undertaken in 61 of the 212 (28%) patients. Fluid for cytologic testing was obtained from all four intra-abdominal quadrants, and biopsies of previously noted sites of disease were performed, in addition to random biopsies of diaphragmatic peritoneum, colonic gutters, and pelvic peritoneum. If present, the retroperitoneal lymph nodes were resected; biopsy specimens of these sites were obtained if there was no evidence of intraperitoneal disease. RESULTS: Findings at second-look laparotomy were negative for cancer in 85 of 151 (56.3%) and positive for cancer in 66 of 151 (43.7%). Only 8 of 151 (5.3%) patients had persistent disease in the pelvis. In the remainder (58/151; 38.4%) disease was found either in the upper abdomen or in the bowel mesentery. Recurrence was documented in the upper abdomen only (71/212; 33.5%), upper abdomen and pelvis (18/212; 8.5%), multiple sites excluding the pelvis (22/212; 10.4%), pelvis only (2/212; 0. 9%), chest alone (5/212; 2.4%), head alone (4/212; 1.9%), or groin alone (2/212; 0.9%). Median survival in the overall group was 51.1 months, with estimated 5- and 10-year survival rates of 44.2% and 32. 9%, respectively. CONCLUSIONS: Modified posterior exenteration is an effective surgical means of eliminating pelvic disease in patients with advanced ovarian cancer. Results of second-look laparotomy confirmed that only 8 of 151 (5.3%) had persistent disease in the pelvis.

Flow cytometric analysis of lymph node metastases in advanced ovarian cancer: clinical and biologic significance.

OBJECTIVE: This study was undertaken to evaluate the deoxyribonucleic acid content and S-phase fraction in advanced epithelial ovarian carcinomas to determine whether lymph node metastases are biologically distinct from peritoneal sites of metastases. STUDY DESIGN: Thirty-five patients with stage III or IV epithelial ovarian cancer who had undergone complete pelvic and paraaortic lymphadenectomy had representative samples from the primary ovarian tumor, peritoneal metastases, and lymph node metastases analyzed by flow cytometry for deoxyribonucleic acid nuclear content and S-phase fraction. RESULTS: Diploid cell lines are found in metastatic lymph nodes (52%) significantly more frequently than in peritoneal metastases (25%, p < 0.02) or in primary ovarian tumors (26%, p < 0.001). The ploidy category frequency distribution of peritoneal metastases mirrors that found in the primary tumor, and both are significantly different from the ploidy category frequency distribution found in metastatic lymph nodes. Heterogeneity among sites is common, being identified in 54% of patients. Peritoneal metastases are more likely to be concordant with the primary tumor (69%) than are lymph node metastases (39%, p < 0.001). Mean S-phase fraction did not differ overall by site but was significantly different between diploid and aneuploid samples by site. Diploid lymph node metastases were found to have the lowest mean S-phase fraction (7.2% +/- 3.3%), and aneuploid lymph node metastases had the highest mean S-phase fraction (22.3% +/- 10.2%). Diploidy of the primary tumor is a positive predictor of long-term survival. Tumoral heterogeneity and lymph node metastases are not related to survival in this group of patients who underwent therapeutic pelvic and aortic lymphadenectomy. CONCLUSIONS: A high proportion of tumor deposits found in metastatic lymph nodes are diploid with a low S-phase fraction. Therapeutic pelvic and aortic lymph node dissection removes disease that, on the basis of flow cytometric characteristics, may be predicted to be resistant to chemotherapy and radiation therapy.

Laparoscopic radical hysterectomy (type III) with aortic and pelvic lymphadenectomy.

OBJECTIVE: The purpose of this study was to incorporate a wide range of operative laparoscopic techniques to complete a type III radical hysterectomy with aortic and pelvic lymphadenectomy. STUDY DESIGN: A type III radical hysterectomy with bilateral aortic and pelvic lymph node dissection was separated into eight component parts: (1) right and left aortic lymphadenectomy, (2) right and left pelvic lymphadenectomy, (3) development of the paravesical and pararectal spaces, (4) ureteral dissection, (5) ligation and dissection of the uterine artery, (6) development of the vesicouterine and rectovaginal spaces, (7) resection of the parametria, and (8) resection of the upper vagina. The adequacy of the component parts was determined and documented on video. RESULTS: Complete aortic and pelvic lymphadenectomy and a type III radical hysterectomy were performed by operative laparoscopy. Argon beam coagulation and countertraction facilitated pelvic and aortic lymph node dissection, including removal of nodal tissue lateral to the iliac vessels. Ureteral dissection with resection of the cervicovesical fascia ("the tunnel") was completed with right-angle dissectors, vascular clips, and argon-beam coagulation. Resection of the cardinal and ureterosacral ligaments was successful by use of Endo-GIA stapling instruments (United States Surgical Corporation, Norwalk, Ct.). CONCLUSION: A complete pelvic and aortic lymphadenectomy and type III radical hysterectomy were performed laparoscopically. This approach could potentially decrease morbidity historically associated with radical hysterectomy and lymphadenectomy performed either abdominally or vaginally. Only prospective randomized trails will allow for the evaluation of potential benefits associated with this surgical technique.

Cost and quality-of-life analyses of surgery for early endometrial cancer: laparotomy versus laparoscopy.

OBJECTIVE: The purpose of this study was to determine whether the cost or quality of life associated with surgical treatment of presumed early-stage endometrial cancer differed on the basis of the surgical approach. STUDY DESIGN: A retrospective analysis was performed on a consecutive series of women with presumed early-stage endometrial cancer treated at the Women's Cancer Center of Northern California. The senior author was the surgeon, cosurgeon, or assistant on all cases. The women comprise two groups with different surgical approaches. The first group of 17 women underwent exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic and aortic lymphadenectomy. The second group of 13 women underwent the same surgery by laparoscopy. The two groups were compared with a two-tailed Student t test. Variables analyzed included age, height, weight, Quetelet index, and predisposing medical problems. Lymph node counts were compiled. Hospital costs were broken down into four cost categories: (1) operating room, (2) hospital bed, (3) pharmacy, and (4) anesthesia. A two-tailed Student t test was also used in this analysis. Issues examined regarding quality of life included (1) average hospital stay, (2) complications, and (3) time to return to normal activity. RESULTS: The patient population differed significantly (p < 0.05) with regard to weight and Quetelet index. The laparotomy group required significantly longer hospitalization than the laparoscopy group (6.3 vs 2.4 days, p < 0.001), resulting in higher overall hospital costs ($19,158 vs $13,988, p < 0.05). Similarly, patients undergoing laparotomy took longer to return to normal activity (5.3 weeks vs 2.4 weeks, p < 0.0001). CONCLUSION: Laparoscopic management of endometrial cancer may result in significant cost savings and improved quality of life as demonstrated by shortened hospital stays and an earlier return to normal activity.

Cytoreductive surgery in advanced epithelial cancer of the ovary: the impact of aortic and pelvic lymphadenectomy.

Beginning in July 1988, a planned program was undertaken to assess the role of aortic and pelvic lymphadenectomy in patients with advanced epithelial cancer of the ovary (Stages IIIa-IVa) undergoing cytoreductive surgery. Our intent was to perform a complete aortic and pelvic lymphadenectomy in all patients in whom we could surgically remove all intra- or retroperitoneal disease measuring 1 cm or greater. Accordingly, 56/77 patients (73%) underwent complete aortic and pelvic lymphadenectomy. The remaining 21/77 patients (27%) did not, either because the lymphadenectomy would not have impacted on the patient's cytoreductive status or because intraoperative conditions precluded it. Positive lymph nodes were found in 36/56 patients (64%). Of these, 23/36 (64%) were macroscopically positive, and if left in situ would have affected the patient's cytoreductive status. Thirteen of 36 (36%) were positive microscopically. Reassessment laparotomy was performed in 44/56 (79%) of the patients having had a lymphadenectomy and is correlated to disease status. Median follow-up is 30 months (range 2-64 months). Survival analysis reveals: 10/20 patients (50%) with negative lymph nodes; 6/13 patients (46%) with microscopically positive lymph nodes; 10/23 patients (43%) with macroscopically positive, but surgically removed lymph nodes; and only 2/21 patients (10%) with residual disease measuring at least 1 cm in diameter are alive without evidence of disease. These preliminary findings suggest that the removal of macroscopically negative lymph nodes offers little benefit to the patient with advanced epithelial cancer and minimal residual (less than 1 cm) disease. However, the concept of cytoreductive surgery, whether it be intra- or retroperitoneal, appears to be validated by the fact that the patients undergoing removal of macroscopically positive lymph nodes have approximately the same chance of survival as those with microscopically positive and/or negative lymph nodes.

Critical reassessment of second-look exploratory laparotomy for epithelial ovarian carcinoma. Minimal diagnostic and therapeutic value in patients with persistent cancer.

From 1979 to 1984, 88 women with epithelial ovarian cancer were treated with surgery and chemotherapy, achieved a clinical complete response, and then had "second-look" exploratory laparotomy to assess the pathologic status of their disease. Persistent cancer was found in 50 (57%) patients: 34 of 50 (68%) had gross tumor, which was larger than 2 cm in 12 (24%) and smaller than 2 cm in 22 (44%), and 16 (32%) had microscopic disease. Salvage therapy was as follows for these patients: whole abdominal irradiation, 29 (58%); chemotherapy, 17 (34%); intraperitoneal chromic phosphate, 1 (2%); and no further therapy, 3 (6%). With a follow-up time of 4 to 8 years, 7 (14%) patients are alive without evidence of cancer, 7 (14%) are alive with disease, 35 (70%) are dead of disease, and 1 (2%) has died of treatment complications. At 5 years, the relapse-free rate was 18% and the survival rate was 25%. Seventy-two parameters of suspected prognostic significance and 64 potential sites of tumor involvement were correlated with survival in a univariate analysis. The factors favorably affecting survival included the following: lower grade; microscopic tumor versus gross disease at second-look laparotomy; removal of the uterus; removal of the omentum; pelvic and paraaortic lymph node biopsy; negative results of a right diaphragm biopsy; and radiation therapy at Stanford University Medical Center, Stanford, California. There was no survival advantage for whole abdomen irradiation compared with chemotherapy or for the patients who had their disease successfully debulked at second-look laparotomy. The above factors and others were evaluated by multivariate regression. The best model (P = 0.000004) for predicting survival included largest tumor mass (P = 0.0002), operative blood loss (P = 0.002), perioperative blood transfusion (P = 0.003), and grade (P = 0.004). The detection of persistent ovarian cancer by second-look exploratory laparotomy should identify a subgroup of patients whose conditions can be salvaged by a second-line therapy. Unfortunately, that subgroup is small (8%) and an effective salvage therapy remains to be identified.

Ovarian fibrosarcoma associated with Maffucci's syndrome.

Maffucci's syndrome, a congenital condition of generalized mesodermal dysplasia, is most often associated with multiple enchondromas and soft tissue hemangiomas or lymphangiomas. This case report describes the development of an unusual ovarian fibrosarcoma and subsequent ovarian adenofibroma in a young woman with the syndrome. The importance of aggressive surveillance in this and similar orthopedic syndromes is stressed.

Epithelial ovarian cancer and the ability to conceive.

Relationships between ovarian cancer and ability to conceive were explored in a case-control study of 188 women with histologically confirmed epithelial ovarian cancer and 539 control women in the San Francisco Bay Area. Control women consisted of two groups: those hospitalized without cancer, matched to cases by age, race, and hospital of diagnosis (n = 280); and those selected from the general population by random digital dialing, matched to cases by age, race, and telephone prefix (n = 259). Ovarian cancer risk among nulliparous (but not parous) women was positively associated with a history of unsuccessful attempts to conceive, of physician-diagnosed infertility, and of doubts about ability to conceive. Among all women, risk increased with increasing years of unprotected intercourse (P value for trend = 0.02). Risk among women having 10 or more yr of unprotected intercourse was 1.8 relative to that among women having less than 2 such yr (P = 0.01). This association was independent of parity, oral contraceptive use, and estimated years of ovulation, each associated with ovarian cancer. Further, duration of unprotected intercourse combined multiplicatively with each of these latter characteristics in increasing ovarian cancer risk. For example, while cancer risk exhibited a 2-fold range from lowest to highest years of unprotected intercourse and a 4-fold range from lowest to highest years of ovulation, risk among women in the highest joint category of these characteristics was 8 times that of women in the lowest category. We believe that some abnormality of ovulation that reduces the likelihood of conception plays a role in epithelial ovarian cancer.

Personal and environmental characteristics related to epithelial ovarian cancer. I. Reproductive and menstrual events and oral contraceptive use.

In two case-control studies conducted in the six-county San Francisco Bay Area, 111 women diagnosed with epithelial ovarian carcinoma in 1974-1977 and 188 women diagnosed in 1983-1985 were interviewed concerning their menstrual, sexual, and reproductive histories. For comparison, interviews were conducted with 752 control women admitted to the same hospitals within six months of the cases; for cases diagnosed in the later period, interviews were also conducted with an additional 259 population-based controls selected by random digit dialing. Controls were matched to cases by age and race. Qualitative and quantitative findings were similar for the two studies. In the combined data, cases were more likely than their matched controls to have been nulliparous, to have undergone menarche at an early age, and to have refrained from using oral contraceptives. Menopause occurred slightly later for cases than for controls, but the differences were not statistically significant. Neither age at first term pregnancy (20 or more weeks gestation) nor number of term pregnancies was predictive of ovarian cancer risk. The protection afforded by oral contraceptive use was independent of parity, and it increased with increasing duration of use. There were no trends in risk with time since last oral contraceptive use or with time since first use, after adjustment for duration of use. These observations suggest that oral contraceptive use decreases risk for ovarian cancer, rather than merely indicates fertility, which may itself decrease risk of developing the disease. The authors combined reproductive characteristics and oral contraceptive use to estimate a woman's total duration of ovulation, which was positively associated with ovarian cancer risk (p less than 0.001 for trend). These observations support the concept that the greater the duration of ovulation or accompanying endocrinologic phenomena, the greater a woman's risk for ovarian cancer.

Personal and environmental characteristics related to epithelial ovarian cancer. II. Exposures to talcum powder, tobacco, alcohol, and coffee.

Vaginal exposures to talc and other particulates may play an etiologic role in epithelial ovarian cancer. Surgical sterilization may protect against ovarian cancer by blocking entry of such particulates into the peritoneal cavity. The authors assessed histories of talcum powder use, tubal sterilization, and hysterectomy with ovarian conservation in 188 women in the San Francisco Bay Area with epithelial ovarian cancers diagnosed in 1983-1985 and in 539 control women. To investigate the roles of blood-borne environmental exposures on ovarian cancer risk, they assessed lifetime consumption of coffee, tobacco, and alcohol in these women. Of the 539 controls, 280 were hospitalized women without overt cancer, and 259 were chosen from the general population by random digit telephone dialing. Ninety-seven (52%) of the cancer patients habitually used talcum powder on the perineum, compared with 247 (46%) of the controls. Adjusted for parity, the relative risk (RR) = 1.40, p = 0.06. There were no statistically significant trends with increasing frequency or duration of talc use, and patients did not differ from controls in use of talc on sanitary pads and/or contraceptive diaphragms. Fewer ovarian cancer patients (7%) than controls (13%) reported prior fallopian tube ligation (RR, adjusted for parity, = 0.56, p = 0.06), and fewer patients (20%) than controls (28%) reported prior hysterectomy (RR = 0.66, p = 0.05). The protective effect of hysterectomy was confined to those who underwent this surgery 10 or more years prior to interview and to those who had not undergone prior tubal sterilization. Consumption of cigarettes and alcohol did not differ between cases and controls. By contrast, 11 (6%) cases never regularly consumed coffee, compared with 31 (11%) hospital controls and 26 (10%) population controls (RR, adjusted for smoking, = 2.2, p = 0.03, for the comparison using all controls). Overall, ovarian cancer risk among women who had drunk coffee for more than 40 years was 3.4 times that of women who had never regularly consumed coffee (p less than 0.01). However, the data exhibited no clear trends in risk with increasing consumption. Although risk ratios relating duration of coffee drinking to ovarian cancer were unaffected by adjustment for several characteristics, further study is needed to exclude potential confounding by other unmeasured characteristics.

Advanced epithelial ovarian cancer: salvage whole abdominal irradiation for patients with recurrent or persistent disease after combination chemotherapy.

Between 1979 and 1984, 53 patients received whole abdominal irradiation in a curative salvage effort for residual (32 patients) or recurrent (21 patients) epithelial ovarian cancer after combination chemotherapy (cisplatin-based in 48 patients). Residual cancer less than or equal to 2 cm in diameter was confirmed at operation in all patients before irradiation consisting of 2,550 to 3,000 rad to the whole abdomen with partial liver/kidney shielding and boosting of the dose to the diaphragmatic/paraaortic nodal regions and pelvis to approximately 4,000 and 5,000 rad, respectively. Twelve patients (23%) did not complete therapy as a result of hematologic intolerance. Actuarial overall and disease-free survival at 3 years are 35% and 30%, respectively, with follow-up for disease-free patients ranging from 30 to 79 months (median, 43 months). Twenty-seven of 36 relapses (75%) occurred within the irradiated abdomen alone. At 3 years, 70% of patients with well- or moderately-differentiated tumors were disease-free v 10% of those with poorly differentiated tumors (P less than .001). Among prognostic factors evaluated, including grade, initial residual disease before chemotherapy, residual disease at time of irradiation, age, chemotherapy response v progression, and completion of irradiation, only grade and initial residual disease before chemotherapy were statistically significant in multivariate analysis (both P less than .01). Patients with the combination of high-grade tumor, initial residual disease greater than 2 cm before chemotherapy, and macroscopic disease after "second-look" laparotomy do not benefit from irradiation. Eleven patients (21%) developed an apparent treatment-related bowel obstruction after completion of irradiation. Selected subsets of patients do well; however, the role of irradiation in this setting can be confirmed only with randomized clinical study.

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.

Therapeutic approaches to uterine papillary serous carcinoma: a preliminary report.

Uterine papillary serous carcinoma (UPSC) is a recently identified and characterized unique histopathologic subtype of endometrial cancer. Unlike the more common types of endometrial cancer, UPSC has a high likelihood of transperitoneal seeding and upper abdominal recurrence. Since our initial report of 26 patients with UPSC, an additional 10 patients with FIGO stage I disease have been diagnosed, operatively staged, and managed by an individualized approach. Operative staging revealed 5 of the 10 patients to have more advanced disease than had been determined clinically. Adjuvant postoperative abdominopelvic radiation was administered to 6 patients, 4 of whom remain free of disease within the treated area. Two patients received adjunctive hormonal and chemotherapy; neither has recurred. Two patients received no adjunctive therapy. One of these failed initially in the vagina with subsequent recurrence in the lungs and supraclavicular nodes. The value of operative staging and selection of appropriate adjunctive therapy awaits additional patient accrual and follow-up.

High-dose megestrol acetate therapy of ovarian carcinoma: a phase II study by the Northern California Oncology Group.

The activity of high-dose megestrol acetate was studied in 47 patients with epithelial ovarian cancers after failure of initial chemotherapy. The dose of megestrol acetate was 800 mg/d orally (PO) for 4 weeks and then 400 mg/d until tumor progression. Patients generally had far-advanced disease. Prior therapy included cisplatin, doxorubicin, and cyclophosphamide (PAC) or other cisplatin-containing regimens in 37, other combinations in eight, and single agents in only two patients. Seventeen patients (36%) developed intestinal obstructions within the first 2 months on study. Tumor histology was serous in 37, endometrioid in six, and clear-cell in two. Two thirds of the tumors were histologic grade 3, and the others were grade 2. Complete remission was obtained in one patient, with time to progression of 4 months. There were three partial remissions, with times to progression of 4, 5, and 18 months. The overall response rate (complete and partial) was 8%. Three additional patients had minor remissions (3, 5, and 8 months), and five had stable disease, for 3, 4, 5, 6, and 9 months. There was no correlation of response with grade, histologic type, or site of disease, but responding patients had a longer survival from diagnosis to protocol entry and from protocol failure to death than did nonresponding patients. The major side effect of megestrol acetate was increased appetite, which caused one patient to withdraw from the study, and resulted in a 10- to 20-kg weight gain in five patients. Plasma levels of megestrol acetate averaged 600 ng/mL in the first month of therapy and decreased to approximately 400 ng/mL at 8 and 12 weeks, after the drug dosage had been reduced. Serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were markedly lower during megestrol therapy compared with pretreatment values. Megestrol acetate at 1 microgram/mL in vitro inhibited soft agar colony formation from one of 17 specimens of ovarian carcinomas. We conclude that megestrol acetate in high doses has modest, but definite, palliative effects in some patients with advanced ovarian carcinoma in whom chemotherapy has failed. A controlled trial of megestrol plus combination chemotherapy as first-line treatment of advanced ovarian carcinoma should be considered.

Ovarian epithelial tumors of borderline malignancy. A clinical and pathologic study of 109 cases.

One hundred nine cases of ovarian tumors of low malignant potential (borderline tumors) diagnosed at Stanford University Medical Center from 1958 to 1982 were reviewed. The patients ranged in age from 10 to 79 years (mean, 40.5 years). The histologic types and corresponding stages of these neoplasms were 73 serous (Stage IA: 35 patients; Stage IB+C: 16 patients; stage II: 8 patients; Stage III: 14 patients), 30 mucinous (Stage IA: 27 patients; Stage IB+C: 3 patients), and 6 mixed seromucinous (all Stage IA). Borderline endometrioid, clear cell, and Brenner tumors were excluded. Follow-up information from 3 to 27 years from the time of initial diagnosis (mean, 7.6 years; median, 7.1 years) revealed that 89 patients are alive without further evidence of neoplasm, and three patients died of unrelated disease without recurrent tumor. Seventeen patients have developed persistent or recurrent neoplasms in the contralateral ovary (six patients) and/or elsewhere within the peritoneal cavity (15 patients) at 5 to 226 months (mean, 61 months) after the initial excision. All of the second neoplasms were borderline serous or seromucinous tumors histologically identical to the original tumor; none of the borderline mucinous tumors recurred. Patients who initially had Stage III borderline serous tumors developed persistent or recurrent neoplasms more commonly (64%) than did patients with lower stage tumors (12%). No correlation was found between the development of a subsequent serous neoplasm and patient age, the primary tumor size, or any single histologic feature. Following treatment of the subsequent neoplasms, 13 patients are free of neoplasm, one patient is alive with tumor, one patient has died of intercurrent disease with tumor, and two patients have died with widespread abdominal tumor 53 and 232 months after their initial diagnosis. These findings confirm the excellent prognosis for patients with borderline serous tumors, despite involvement of the peritoneal cavity and the development of recrudescent tumor, although long-term follow-up is indicated. Mucinous borderline tumors, as defined by published criteria, almost invariably present as localized (low-stage) tumors and, in our experience, do not recur when confined to the ovary.

Epithelial ovarian carcinoma in patients with intersex disorders: the role of pituitary gonadotropins in ovarian tumorigenesis.

The common epithelial tumors of the human ovary have rarely been found in the gonads of intersex patients with gonadal dysgenesis or true hermaphroditism. This report describes a patient with ovarian serous cystadenocarcinoma and mixed gonadal dysgenesis (45,X/46,XY) and reviews other reported cases. Intersex patients require early evaluation with treatment based on the karyotypic risk of malignant gonadal transformation. Epithelial ovarian tumors arising in dysgenetic gonads, which lack ova and are incapable of ovulating, provide a unique model for understanding the role of pituitary gonadotropins in ovarian epithelial tumorigenesis.

Advanced epithelial ovarian cancer: toxicity of whole abdominal irradiation after operation, combination chemotherapy, and reoperation.

Thirty-five patients with advanced ovarian cancer have received, as salvage therapy, irradiation consisting of 30 Gy to the entire abdominal contents with partial liver/kidney shielding and boosts to 42 and 51 Gy for the paraaortic/diaphragmatic and pelvic regions, respectively. These patients had received 6 to 25 cycles (median, 11 cycles) of prior combination chemotherapy (included cisplatin in 30), with "second-look" laparotomy performed in 33; 24 (68%) had three or more laparotomies. Acute gastrointestinal toxicity was generally mild. Significant hematologic toxicity (leukocytes less than 2000/mm3; or platelets less than 100,000/mm3) was seen in 19 (54%); platelet suppression occurred in 18 of these 19. Nine patients failed to complete the prescribed course of therapy; in seven, this was secondary to hematologic toxicity. Amount of prior chemotherapy and advanced age correlated with degree of hematologic toxicity. Five patients without evidence of disease (laparotomy confirmed) have developed treatment-related bowel obstruction. No other chronic toxicity of clinical significance has been observed. Seven patients have developed bowel obstruction associated with progressive neoplasm. Irradiation was well tolerated symptomatically, but hematologic toxicity associated with prior chemotherapy prevented its completion in 20% of patients. Clinical manifestations of radiation bowel toxicity have been moderate to date and should be interpreted in the context of the aggressive combined modality program.

A critical reassessment of second-look laparotomy in epithelial ovarian carcinoma.

Eighty-eight women with epithelial ovarian carcinoma, treated by first-line chemotherapy, achieved a complete clinical response and underwent second-look laparotomy to assess the true pathologic status of their disease. Persistent tumor was found in 50 patients (57%). Thirty-two of these (36%) had obvious gross tumor, whereas, 16 (18%) had microscopic disease. Thirty-eight patients (43%) had no pathologic evidence of persistent ovarian carcinoma. With a follow-up of 6 to 60 months, 30 of these patients (79%) remain without evidence of recurrence. Multivariate logistic regression analysis revealed three covariates that were independently significant in predicting continued disease-free status. These included: the greatest diameter of the largest residual tumor left at the primary operation; histologic features of the tumor; and the diameter of the largest tumor aggregate found at initial operation. A mathematical model based on the most significant covariates was designed to assess the relative risk of any patient having persistent tumor at second-look laparotomy. A comparison of the predicted to actual outcome revealed a sensitivity of the model of 88%, a specificity of 71%, and an accuracy of 77%. Second-look laparotomy represents the basis on which potentially curative second-line salvage therapy can be initiated. With an increasing period of follow-up and with greater numbers of patients, it can potentially document a complete pathologic response to first-line therapy administered with curative intent, and identify patients for additional, adjunctive therapy, who are at risk of recurrence.

Conservative treatment of borderline ovarian tumors.

Of 61 patients with stage IA borderline ovarian tumors, 41 were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy, and 20 were treated by a variety of more limited operations, including cystectomy with (one patient) and without (three patients) a contralateral ovarian wedge biopsy, and unilateral salpingo-oophorectomy with (six patients) and without (ten patients) a contralateral wedge biopsy. In the group treated conservatively, there were 11 serous, seven mucinous, and two mixed seromucinous borderline tumors, whereas in the total abdominal hysterectomy and bilateral salpingo-oophorectomy treatment group there were 26 serious, 12 mucinous, and three mixed seromucinous borderline tumors. After a mean follow-up of 89 months (range 36 to 244 months), subsequent borderline neoplasms had developed in three patients (15%) with serious borderline tumors initially treated conservatively and in two patients (5%) with serous or mixed seromucinous borderline tumors initially treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. No patient with a mucinous borderline tumor treated either conservatively or with total abdominal hysterectomy and bilateral salpingo-oophorectomy developed a subsequent neoplasm. All 61 patients in the study group are alive and free of disease, including those who developed recurrent neoplasm.