P.J. DiSaia

A prospective surgical pathological study of stage I squamous carcinoma of the cervix: A Gynecologic Oncology Group study

Thirty-three institutions collaborating in the Gynecologic Oncology Group gathered surgical and pathological data on 1125 patients with primary, previously untreated, histologically confirmed stage I cervical carcinoma with more than 3 mm of invasion who were selected to undergo radical hysterectomy and paraaortic and pelvic lymphadenectomy. Of the 940 eligible, evaluable patients, 732 had squamous carcinoma. Of the study group, 87 (12%) did not undergo radical hysterectomy because of gross disease beyond the uterus or microscopic aortic node involvement documented at exploratory laparotomy. Among the 645 patients undergoing pelvic and paraaortic lymphadenectomy and radical hysterectomy, five risk factors were significantly associated with microscopic pelvic lymph node metastasis: depth of invasion (P = 0.0001), parametrial involvement (P = 0.0001), capillary-lymphatic space invasion (P = 0.0001), tumor grade (P = 0.01), and gross versus occult primary tumor (P = 0.009). The factors identified as independent risk factors for pelvic lymph node metastasis by multivariate analysis were capillary-lymphatic space involvement (P less than 0.0001), depth of invasion (P less than 0.0001), parametrial involvement (P = 0.0005), and age (P = 0.02). The model was used to predict the chance of a patient having nodal metastasis for any combination of risk factors.

Conservative management of extramammary Paget's disease of the vulva

Patients with extramammary Pagets disease of the vulva at the University of California--Irvine Medical Center and the Memorial Medical Center of Long Beach Womens Hospital between 1976 and 1986 were treated with nonradical surgery. These 14 patients were analyzed in a retrospective fashion to determine if conservative management was successful in eradicating the disease process while preserving appearance and sexual function. All patients were treated with nonradical surgery: skinning vulvectomy with split-thickness skin graft (86%), hemivulvectomy (7%), and simple vulvectomy (7%). In all cases intraoperative frozen-section analysis of surgical margins was performed to determine the extent of disease and outline the margins of resection. No patients had Pagets disease associated with an underlying adenocarcinoma. Three patients developed recurrent Pagets disease. Two of these patients recurred at the site of a positive margin and thus represent persistent disease. Only one patient (7%) had recurrent disease in the face of negative margins. The median duration of follow-up was 50 months. All patients are presently free of disease. The rationale for this conservative management is discussed.

In vitro cytotoxicity of human recombinant tumor necrosis factor α in association with radiotherapy in a human ovarian carcinoma cell line

It has been speculated that tumor necrosis factor alpha (TNF-alpha) may decrease the cytotoxicity of radiotherapy by increasing the scavenging of toxic superoxide radicals. Because of the possible clinical implications, the cytotoxicity of TNF-alpha in combination with radiotherapy (RT) was compared with that of RT alone in a human ovarian cancer cell line. NIH:OVCAR-3 cells were incubated with TNF-alpha at 10.0, 1.0, 0.1, and 0.01 microgram/ml. Plates were divided into two groups; one received 150 cGy of radiotherapy and the other received no further therapy. Seventy-two hours later, supernatants were aspirated and viable cells were stained with a 1% solution of crystal violet. Survival of cells treated with RT plus TNF-alpha was expressed as a percentage of surviving irradiated controls. Analysis of results revealed minimal additive cell killing effect between TNF-alpha and radiotherapy at all concentrations of tumor necrosis factor, with the greatest difference noted in the group treated with 10 micrograms/ml TNF-alpha. A continued radiotherapy dose-response study with TNF-alpha showed a similar additive, not radioprotective, effect. This may have implication as a potentiator of RT in some human tumors.

Use of a murine model for comparison of intravenous and intraperitoneal cisplatin in the treatment of microscopic ovarian cancer

The most effective method for the delivery of cisplatin chemotherapy in the treatment of epithelial ovarian cancer limited to the presence of microscopic intraperitoneal disease is a controversial issue. The use of intravenous (iv) versus intraperitoneal (ip) cisplatin was evaluated in a murine tumor model of human epithelial ovarian cancer. Using single dose cisplatin therapy for microscopic disease limited to positive cytology of abdominal disease and microscopic peritoneal involvement, ip therapy had significantly greater (P less than 0.001) survival time than iv therapy (28 +/- 1.6 days vs. 23 +/- 1.6 days, respectively). Once ascites and macroscopically evident intraperitoneal tumor became apparent, no difference could be found in survival time based on iv versus ip therapy (16 +/- 3 days for both groups); though both forms of therapy significantly (P less than 0.05) prolonged survival in mice with macroscopic disease when compared to control animals (13 +/- 1.2 days). The evidence presented implies that ip cisplatin therapy is significantly more effective than iv therapy when dealing with microscopic intraperitoneal disease.

Management of endometrial cancer with suspected cervical involvement

The 1989 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer calls for operative assessment of the extent of uterine disease, grade, and sites of metastasis before assigning a stage to the cancer. In the current study, 70 endometrial cancer patients with suspected cervical involvement based on a positive endocervical curettage or punch biopsy were treated with initial surgery followed by tailored radiation or chemotherapy. Only 37% of the patients had operative findings consistent with the preoperative suspicion of stage II disease. Postoperative therapy was determined by the extent of cervical involvement, depth of myometrial invasion, cell type, tumor grade, and the presence and location of extrauterine disease. Based upon these parameters, 21 patients were believed to have low risk for pelvic recurrence and received no adjuvant therapy (90% 5-year survival); 38 patients received postoperative pelvic radiation because of high-risk factors for pelvic recurrence or pelvic nodal involvement (65% 5-year survival); and 11 patients received chemotherapy and/or extended radiation because of extrapelvic disease (no 5-year survivors). The approach outlined supports initial surgery for cases of endometrial cancer with suspected cervical involvement. This approach permits accurate surgical staging under the new FIGO system, avoids radiotherapy in many patients whose disease is less extensive than suspected preoperatively, and can accomplish good local control with limited morbidity.

A perspective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group study

‘Division of Gynecologic Oncology, Georgetown University, Vincent T. Lombardi Cancer Research Center, 3800 Reservoir Road, NW, Washington, DC ’ Roswell Park Memorial Institute, Buffalo, New York 3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514 ’ Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Indiana University Medical Center, Indianapolis, Indiana 46202 ’ Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Miami School of Medicine, Miami, Florida 6 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina ’ Department of Obstetrics and Gynecology, University of Colorado Health Sciences Center, and Gynecology Tumor Service, Denver General Hospital, Denver, Colorado a Department of Obstetrics and Gynecology, University of California, Irvine Cancer Center, Orange, California 9 Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey, Pennsylvania 17033

Extraovarian peritoneal serous papillary carcinoma: A case‐control retrospective comparison to papillary adenocarcinoma of the ovary

Since the establishment of extraovarian peritoneal serous papillary carcinoma (EPSPC) as a clinical entity in 1959, less than 250 cases have been described and its clinicopathologic features remain obscure. The present series is a retrospective, case-controlled study comparing the response and survival to cytoreductive surgery followed by cisplatin-based multiagent chemotherapy of 33 women with confirmed EPSPC versus 33 cases with papillary serous ovarian cancer (PSOC). Each EPSPC case was matched to a PSOC control for extent and distribution of disease prior to and following cytoreductive surgery, tumor grade, patient age, and treatment. Additionally, the new Gynecologic Oncology Group criteria for the diagnosis for EPSPC are discussed. There were no significant differences in tumor response to therapy, disease-free interval, and actuarial survival between cases and controls. These data suggest that EPSPC is clinically similar to PSOC and support the need for a prospective clinical trial to compare these two entities further.

Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy

Schink J.C.; Singh D.K.; Rademaker A.W.; Miller D.S.; Lurain from the anus in the control group; all 7 women with anal HPV J.R. 16 had concomitant cervical infection. The role of anal examiUSA nation in the assessment of women with any focus of genital inOBSTET GYNECOL 1992 80/5 (817-820) traepithelial neoplasia requires further investigation. Objective: To evaluate the efficacy and toxicity of a regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine in patients with metastatic, high-risk gestational trophoblastic tumors. Methods: Twelve women with metastatic gestational choriocarcinoma received 64 treatment cycles. All met the National Cancer Institute criteria for high-risk gestational trophoblastic tumors. Response was evaluated by monitoring serial serum &hCG levels. Toxicity was recorded using standard World Health Organization criteria. Results: There was no life-threatening toxicity. Neutropenia necessitating a l-week delay of treatment occurred with only eight treatment cycles (12.5%) and deferral of vincristine and cyclophosphamide with three cycles. Anemia requiring transfusion complicated only two cycles. Peripheral neuropathy in two patients was treated by discontinuing vincristine. Other toxicities included nausea and vomiting, diarrhea, stomatitis, alopecia, conjunctivitis, thrombocytopenia, and fever. Ten of the 12 subjects experienced a complete response. Two had partial responses and one with an initial complete response had relapse 4 months after completing therapy; all three were successfully salvaged with cisplatin-based chemotherapy. Overall survival was lOO%, and all 12 patients are disease-free with a median follow-up of 26 months. Conclusions: Chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine is well tolerated and highly effective for metastatic, high-risk gestational trophoblastic disease. Bulky stage IB cervical carcinoma managed by primary radical hysterectomy followed by tailored radiotherapy Bloss J.D.; Berman M.L.; Mukhererjee J.; Manetta A.; Emma D.; Ramsanghani N.S.; DiSaia P.J. USA GYNECOL ONCOL 1992 47/l (21-27) The management of bulky, stage IB cervical carcinoma remains controversial. The present study reports the outcome of 84 women treated by radical hysterectomy, in which the surgical specimen revealed a lesion measured to be 4 cm or greater in size following formalin fixation. Of the 84 women, 42 (50%) received postoperative radiotherapy based on additional surgical findings beyond tumor size suggesting a high risk for pelvic recurrence including lymph node metastasis, parametrial spread, and compromised margins. Despite the bulky nature of these lesions, major operative and early postoperative complication rates were low (6%). Delayed complications including fistulas and bowel obstructions occurred in only 2.4% of patients treated with surgery alone and in 14.2% of women treated with combined therapy. Corrected 5-year survival in this series was 70.4% (75.6% in the surgery only group and 65.0% in the surgery plus radiotherapy group). Recurrence and mortality rates were related to lesion size, with most recurrences and deaths occurring in women with lesions measuring 6 cm or greater. Comparison of these data utilizing primary radical hysterectomy followed by tailored radiotherapy with previously published data on similar groups of high-risk patients treated with either radiotherapy alone or with radiotherapy followed by simple hysterectomy suggests comparable survival and morbidity. Anal intraepithelial neoplasia: Part of a multifocal disease process Scholefield J.H.; Hickson W.G.E.; Smith J.H.F.: Rogers K.; Sharp F. GBR LANCET 1992 340/8830 (1271-1273) Invasive carcinomas of the anogenital epithelium share a common etiological factor human papillomavirus (HPV) type 16. Although genital intraepithelial neoplasia may be multifocal, there have been no studies of the prevalence of anal intraepithelial neoplasia in women with intraepithelial neoplasia of the genital tract. We tested the hypothesis that women with high-grade cervical intraepithelial neoplasia are at higher risk of disease in the anus than are control women of similar age with no history of anogenital neoplasia. 29 (19%) of 152 women with cervical intraepithelial neoplasia grade III had histological evidence of anal intraepithelial neoplasia. Of the 29 patients, 11 had grade III anal lesions; 2 of those women had concomitant invasive anal squamous cell carcinomas. Only 7% (8/l 15) women with high-grade lesions of the cervix alone had evidence of anal intraepithelial neoplasia; by contrast, 57% (2 1137) of those with more than one focus of intraepithelial neoplasia (cervix plus vulva, vagina, or both) had anal lesions. HPV 16 DNA was identified in 18 (51%) of 35 anal biopsy samples in the study group. No evidence of anal intraepithelial neoplasia was found in the control group (50 women), although 2 patients had grade I cervical lesions. HPV 16 DNA was identified in 12 (24%) of biopsy samples from the cervix and 7 (14%) Percutaneous nephrostomy and ureteral stenting in gynecologic malignancies Barton D.P.J.; Morse S.S.; Fiorica J.V.; Hoffman M.S.; Roberts W.S.; Cavanagh D. USA OBSTET GYNECOL 1992 8015 (805-811) Objective: To identify the indications, complications, and efficacy of percutaneous nephrostomies and ureteral stents in women with gynecologic cancer. Methods: In a retrospective study, 40 women underwent urinary diversion with percutaneous nephrostomy and ureteral stents. Nine had ureteral stenosis on initial presentation, 18 had persistent or recurrent cancer, nine had no evidence of disease, and four had operative ureteral damage. Of the nine who were without disease, seven had a urinary conduit. Results: Thirty-five patients had ureteral stenosis, which was bilateral in 24, and five had a ureteral Iistula. Sixteen had a unilateral and 22 had bilateral percutaneous nephrostomies, with two cases having stents only. The most common complication was hematuria. Thirteen women were later hospitalized for pyelonephritis. Twenty-nine (72.5%) had ureteral stents, which were bilateral in 12. Renal function was abnormal in 26, but improved in 14 and returned to normal in six. Five Iistulas were managed with ureteral stents alone and

Radical hysterectomy in the elderly patient: Analysis of morbidity

OBJECTIVE This study compares the perioperative morbidity and mortality following radical hysterectomy of patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA. STUDY DESIGN A retrospective analysis of morbidity and mortality for the first 60 postoperative days was conducted. The study population of 45 women greater than 65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women less than 65 years treated similarly. RESULTS In the elderly group, 31 of 45 and 12 of 15 were American Society of Anesthesologists Physical Status II and III respectively; 68/90 and 19/90 were American Society of Anesthesiologists status I and II in the younger age group (p = 0.001). Transfusions of greater than 2 units were required in 14% of the elderly and 35% of younger patients (p = 0.02). No statistical differences were observed between groups for other parameters examined. CONCLUSION Age alone should not be a contraindication for radical hysterectomy in the elderly patient with American Society of Anesthesiologists Physical Status I to III.