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The study aims to compare the difference in treatment and survival between White (W) and African American (AA) patients with vaginal cancer (VC).Patients with a diagnosis of invasive vaginal cancer were identified from Surveillance, Epidemiology, and End Results (SEER) program from 1988 to 2007 and were divided into White (W) and African American (AA) subgroups. Student's t test, Kaplan-Meier survival methods, and Cox regression proportional hazards were performed.A total of 2675 patients met the inclusion criteria, with histologic distribution of squamous cell carcinoma (SCC; 2190, 82%) and adenocarcinoma (AC; 485, 18%); 2294 (85.8%) were W, and 381 (14.2%) were AA. Median age was 69 for W and 65 for AA (p0.001). SCC and AC were equally distributed between W and AA. Advanced stage disease (FIGO III and IV) was more prominent in AA compared with W (30.4% vs. 23.1%, p=0.019). Radiation therapy was utilized equally in both racial groups; however, surgical treatment alone or combined with radiation therapy was more frequent in W compared with AA (27.7% vs. 17.5%, p0.001). The 5-year survival was 45% in W and 38.6% in AA (p=0.008). In multivariate analysis, AA had significantly poorer survival compared with Whites when controlling for age, histology, stage, grade and treatment modality (HR 1.2, 95% CI 1.1-1.4, p=0.007).African American women with vaginal cancer were more likely to present, at a younger age, advanced stage and less likely to receive surgical treatment. Our data suggests that AA race is an independent predictor of poor survival in vaginal cancer.

Objective. To characterize clinical features of vulvar Paget's disease, and examine the quantity of immunosuppressive regulatory T-cells in vulvar Paget's tissue. Methods. Vulvar Paget's cases from 1992 to 2007 from two institutions were identified by pathology database search. Regulatory T-cells were identified with FOXP3 immunohistochemistry and quantified at the dermal–epidermal junction using image analysis software. Thirteen non-neoplastic inflammatory cases were stained for comparison. Results. Cases included 33 women treated for primary vulvar Paget's, and 7 referred at recurrence. Of the 24 primary cases with greater than 5months follow-up, recurrence was documented in 12/24(50%). Eight women (20%) recurred multiple times, but no recurrences were invasive. Significantly more patients with positive margins developed recurrent disease (82% vs 23%, p =0.01). Secondary neoplasms occurred in 10/40(25%). FOXP3+ cells at the dermal–epidermal junction were quantified in 29 primary and 13 recurrent tissue samples. FOXP3+ cells were absent in surrounding normal vulvar skin. FOXP3+ cells averaged 66/HPF in primary vulvar Paget's and 66/HPF in recurrent Paget's, compared to 22/HPF in non-neoplastic inflammatory cases ( p =0.0003, p =0.001). Primary cases with positive surgical margins had more FOXP3+ cells than those with negative margins (85 vs 49, p =0.01). Recurrent cases with positive margins had more FOXP3+ cells than negative cases (84 vs 33, p =0.06). FOXP3 levels in primary specimens were higher in cases which recurred (78 vs 35, p =0.02). Conclusions. Increased regulatory T-cells may be associated with more extensive cases of vulvar Paget's disease that result in positive surgical margins and are associated with recurrence of disease, suggesting immunosuppression as a key factor.

Objective. To determine whether tumor size or morphology is predictive of extrauterine disease and/or recurrence risk in endometrial cancer and therefore guide decisions about the necessity of complete surgical staging and adjuvant therapy. Methods. All women with surgically treated endometrial carcinoma between 1 January 1990 and 1 January 2000 were eligible. 345 patients were eligible for retrospective chart review. Univariate and multivariate logistic regression models were used to determine the predictors of nodal metastasis and recurrence. Results. As tumor size increased, the risk of nodal metastasis increased. However, a risk of nodal metastasis remained even with small lesions less than or equal to 2 cm (6.3% risk). Patients with tumor size greater than 2 cm had a 26.3% incidence of nodal metastasis. In univariate analysis, the odds ratio (OR) for tumor size as a predictor of extrauterine disease was 1.4 (95% CI 1.2–1.6). In multivariate analysis, tumor size was not statistically significant. Only the lesions greater than or equal to 8 cm confer a risk that approaches previously identified well-known predictors. Tumor size was not found to be a statistically significant predictor of recurrence OR 1.3 (1.0–1.8). Conclusions. Tumor size correlates with extrauterine disease, but it is not an independent prognostic variable. Although the risk of extrauterine disease increases with tumor size, the risk of nodal metastases remains even for those patients with very small tumors, underscoring the need for routine complete surgical staging. Tumor size does not appear to be an independent predictor of recurrence.

Objective. Glassy cell carcinoma (GCC) of the cervix has traditionally been characterized as an aggressive histologic subtype with poor outcomes. An earlier series from our institution supported a grim prognostic outlook, demonstrating a survival rate of only 55% in women with stage I disease. We present a comparison of a contemporary series of patients with GCC. Methods. All cases of GCC treated from 1993 to 1999 identified by our tumor registry were reviewed for a variety of clinicopathologic features, treatment strategies, and outcome. Results. A total of 403 cases of invasive cancer of the cervix were identified. There were 22 patients with histologically confirmed GCC, representing only 5.4% of all cervical cancer diagnoses. Patients with GCC had an overall survival of 73% (16/22) and a disease-free survival of 64% (14/22). The incidence of stage I lesions was 64% (14/22). Overall survival of patients with stage I disease was 86% (12/14), with a disease-free survival of 71% (10/14) at a median follow-up of 28.5 months. Seven stage IB lesions were treated with surgery alone, whereas six received adjuvant radiation or chemoradiation following surgery. Two patients in each treatment group recurred, yielding an overall recurrence rate of 29% (4/14). However, of those who recurred with stage I disease, all 4 patients had two or more intermediate risk factors (lymph–vascular space invasion [LVSI], deep tumor invasion, or tumor size greater than 3 cm). Conclusions. Glassy cell carcinoma of the cervix appears to have a better prognosis than previously reported. We observed that intermediate risk histopathologic features identified in squamous cell cohorts are also predictive of a poorer outcome in patients with GCC. Thus, patients with LVSI, deep stromal invasion, and large tumor size are at the highest risk for pelvic relapse and should be candidates for adjuvant treatment.

Little is known about the etiology of in situ or invasive squamous cell cancer of the vagina. It is thought that some vaginal cancers may have the same etiology as cervical cancer. It is also not known whether in situ and invasive vaginal cancer share the same etiologic factors. We conducted a study to evaluate risk factors for in situ and invasive vaginal cancer and their potential relationship to prior exposure to human papillomaviruses (HPV).A population-based case-control study included 156 women with squamous cell in situ or invasive vaginal cancer diagnosed between January 1981 and June 1998 and 2041 control women identified through random-digit dialing in western Washington state. Cases and controls were interviewed in person and provided blood samples; archival tumor tissue was retrieved for cases. Blood samples were tested for antibodies to HPV, and tumor tissue was tested for HPV DNA.Women with vaginal cancer were more likely to have five or more lifetime sexual partners (OR = 3.1, 95% CI 1.9 to 4.9), to have an early age at first intercourse (17 years OR = 2.0, 95% CI 1.2 to 3.5), and to be current smokers at diagnosis (OR = 2.1, 95% CI 1.4 to 3.1) than control women. Approximately 30% of all cases had been treated for a prior anogenital tumor, most often of the cervix. Prior hysterectomy was a risk factor only among women who had no history of prior anogenital cancer (OR = 3.9 95% CI 2.5 to 6.1). Antibodies to HPV16 L1 were strongly related to risk of vaginal cancer (OR = 4.3, 95% CI 3.0 to 6.2). We detected HPV DNA in tumor blocks from over 80% of the patients with in situ and 60% of the patients with invasive cancers.In situ and invasive vaginal neoplasia have many of the same risk factors as cervical cancer, including a strong relationship to HPV infection. Women who have been treated for a prior anogenital cancer, particularly of the cervix, have a high relative risk, although low absolute risk, of being diagnosed with vaginal cancer.

The aim of this study was to evaluate the impact of total radiation dose on residual tumor and the prognostic significance of persistent disease in women with bulky, barrel-shaped cervical carcinoma who received definitive radiation followed by adjuvant hysterectomy.The medical records of 57 patients with bulky endophytic cervical carcinoma treated at the University of Washington between 1976 and 1997 were reviewed. All patients received external beam pelvic radiotherapy supplemented by intracavitary brachytherapy, followed by extrafascial hysterectomy 6 to 8 weeks later.The mean pretreatment tumor diameter was 5.9 cm, with a range of 4-9 cm. Total radiation dose to point A ranged from 5040 to 9700 cGy, and the mean for the group was 7966 cGy. Residual disease was present in 35 (61%) of the hysterectomy specimens. The frequency of cervical tumor sterilization correlated significantly with the mean radiation dose to point A (P = 0.016). Patients without histologic residual disease had a significantly improved outcome, with 95% of patients remaining clinically free of disease at last follow-up, versus 31% of those with residual disease (P0.001). As expected, the pelvic control rate was excellent (100%) in patients with complete tumor eradication compared to the group with residual tumor (44%). Those with no residual disease enjoyed a significantly improved survival compared to those with residual tumor (P0.001). Furthermore, a statistically significant higher survival was realized in patients harboring only microscopic residual compared to those with either macroscopically evident tumor residuum and/or positive surgical margins (P = 0.036).Higher radiation doses are associated with an improved likelihood of tumor eradication in the treatment of bulky, endophytic cervical cancer and complete tumor sterilization at adjuvant hysterectomy is predictive of significantly enhanced survival and pelvic control. The high rate of histologic tumor persistence in our series emphasizes the need for more efficacious therapies in patients with bulky endophytic cervical cancer and argues for escalation of radiation dose even when adjuvant hysterectomy is planned.

Objectives. Surgicopathologic evaluation of the scalene fat pad is considered a critical step in the pretreatment evaluation of patients at our institution with cervical or corpus carcinoma when the periaortic lymph nodes (PAN) are involved. However, enthusiasm for this procedure at other centers has waned, largely due to a wide discrepancy in the reported rates of occult scalene node involvement. In an attempt to clarify the benefit of pretreatment scalene node sampling in gynecologic malignancies, we present our experience over the past 18 years. Materials and methods. We identified 57 patients who underwent scalene node sampling between 1980 and 1998. In 39 of 49 (80%), the decision to proceed with scalene node sampling was based entirely on histologically documented PAN metastases. In the remainder, scalene node sampling was prompted by the presence of suspicious clinical findings. Results. Of the 49 patients included in the study, 33 had carcinoma of the cervix, while 16 had corpus carcinoma. Ninety percent of scalene node sampling was performed at the time of primary diagnosis. Overall, 9 patients (18%) had scalene node metastases. Notably, not a single patient with corpus cancer was found to have scalene node metastases in the absence of clinically evident scalene node enlargement independent of PAN status. In cervix cancer cases, the presence of grossly involved PAN was predictive of a high likelihood of scalene node metastases (44%), while no patient with occult PAN metastases had involvement of the scalene node. Only 1 minor complication was encountered following scalene node sampling. The 40 scalene node-negative patients were treated with either extended field radiation or whole abdominal radiation therapy, and 20% developed a major, RTOG grade ≥3 complication such as fistula formation, bowel obstruction, or ureteral stenosis. Only 1 case of mild radiation enteritis and cellulitis occurred during palliative radiation in the group of patients with scalene node metastases. Conclusions. Scalene node sampling may be of benefit in the pretreatment evaluation of patients with cervical carcinoma when PAN are grossly involved. Given that scalene node involvement satisfies the criteria for distant metastases, identification of such allows the clinician to avoid the morbidity of extended field radiotherapy in a setting without the chance for cure.

Objective: To compare the antimetabolites methotrexate and 6-mercaptopurine as single-agent medical abortifacients using clinical and immunohistochemical analyses. Methods: Twenty-seven women with gestations less than 7 weeks from the last menstrual period (LMP) were randomized to receive intramuscular methotrexate, 50 mg/m2, or oral 6-mercaptopurine, 200 mg. Forty-six additional women received methotrexate after randomization was discontinued. Women returned at 2-week intervals. Those without fetal cardiac activity were followed until complete abortion. Those with fetal cardiac activity were considered failures and underwent suction abortions. Tissue collected at the time of suction abortion was analyzed with the cell-proliferation immunohistochemical assay Ki-67. Results: All 12 women in the 6-mercaptopurine group had fetal cardiac activity at follow-up and underwent suction abortion; therefore, this arm of the study was discontinued. Six of the 61 women who received methotrexate had fetal cardiac activity at follow-up and also underwent suction abortion. Fetal cardiac activity was present after methotrexate in three of 55 women at less than 6 weeks from the LMP and in three of six between 6 and 7 weeks from the LMP (P < .01). Women who aborted after methotrexate started bleeding on day 19 (standard deviation [SD] 7.8), bled for 9 days (SD 4.0), and used minimal pain medications. Tissues exposed to methotrexate showed decreased Ki-67 activity compared with tissues exposed to 6-mercaptopurine (P = .003). Conclusion: In oral doses of 200 mg, 6-mercaptopurine did not induce early abortion. A single intramuscular dose of methotrexate used without prostaglandins induced abortion in most women at gestational ages of less than 6 weeks. Ki-67 activity was lower in a small sample of fetal tissues exposed to methotrexate than in tissues exposed to 6-mercaptopurine.

Objective: To determine if oncogene overexpression in patients with advanced epithelial ovarian cancer correlates with survival. Methods: Twenty-two women with stage III ovarian cancer, observed for a median of 66 (range 48–204) months were compared with 30 with a median survival of 18 (range 2–28) months. Using immunocytochemistry, tumors were immunostained for overexpression of p53, c-erb-B-2, and epidermal growth factor receptor and were evaluated quantitatively for expression of estrogen receptor, progesterone receptor, and Ki-67 antigen, a marker of cellular proliferation. Results: The median age of long-term survivors was 52 (range 30–76) years compared with 55 (range 36–80) years for short-term survivors. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors compared with seven of the 30 short-term survivors, a significant difference (P = .05). The average level of Ki-67 expression was 43% in long-term survivors and 64% in short-term survivors (P = .007). Overexpression of p53 was seen in 54% of long-term survivors and 80% of short-term survivors (P = .05). A combination of Ki-67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term survivors compared with 68% of short-term survivors (P = .005). Epidermal growth factor receptor, c-erb-B-2, estrogen receptor, and progesterone receptor statuses did not differ significantly between the two groups. Conclusion: Markers that did not correlate with survival included the hormone receptors, estrogen receptor and progesterone receptor, and the oncogenes, c-erb-B-2 and epidermal growth factor receptor. Long-term survivors with advanced ovarian cancer were more likely to have had an optimal cytoreduction and lower levels of Ki-67 antigen expression and were less likely to overexpress p53 than were short-term survivors.

OBJECTIVE: We set out to evaluate the prognostic factors in cervical adenocarcinoma metastatic to lymph nodes. STUDY DESIGN: We performed a retrospective review of 40 patients with cervical adenocarcinoma and lymph node metastasis from 1976 to 1996. RESULTS: Thirty-four patients had adenocarcinoma, and six had adenosquamous carcinoma. Median survival was 50 months. The median survival for patients with stage I disease was 69 months. Stage at diagnosis, treatment with radical hysterectomy, and receiving adjuvant therapy were associated with prolonged survival. A trend toward improved survival was noted with the use of concurrent radiation and chemotherapy as an adjuvant therapy. CONCLUSIONS: Adenocarcinoma metastatic to the lymph nodes does not have a uniformly poor prognosis, especially with early-stage disease. Improved survival was observed with the use of adjuvant therapy, specifically the use of combined chemotherapy and radiation after radical hysterectomy. The optimal therapy in this setting is yet to be determined. (Am J Obstet Gynecol 1998;178:1131-7.)

Objective. Earlier studies have demonstrated that the uterine papillary serous carcinoma (UPSC) variant of endometrial carcinoma has a high recurrence rate, even when disease is apparently confined to the uterus. The current study evaluated survival in patients with surgically staged UPSC. Methods. Patients with UPSC were identified from surgical pathology files and charts were retrospectively reviewed. Only patients who had undergone a TAH–BSO, lymph node dissection, and peritoneal cytology were included. Results. The FIGO stages of the 36 patients were 12 Stage I (4 IA, 4 IB, 4 IC), 2 Stage IIB, 13 Stage III (5 IIIA, 8 IIIC), and 9 Stage IV. Of the 14 Stage I/II patients, 6 did not receive adjuvant therapy, 5 received whole pelvic radiation (WPXRT), and 3 received whole abdominal radiation therapy (WART); after a median follow-up interval of 50 months only 2 (14%) of these Stage I/II patients have developed a recurrence. Both of the recurrences were in Stage IC patients who received radiation; 1 recurred in the radiation field. Of the 5 Stage IIIA patients, 3 patients declined therapy and 2 were treated with WART; 3 patients, including the 2 who received radiation therapy, are alive without disease. Of the 8 Stage IIIC patients, 2 declined postoperative therapy, 2 received WART, and 4 received WPXRT with an extended field to include paraaortic nodes. Four of the 6 Stage IIIC patients treated with curative intent are without evidence of disease and 1 died of unrelated causes after a median follow-up interval of 48 months. Both of the Stage IIIC patients who declined treatment recurred. Of the 9 patients with Stage IV disease, 8 have died of disease. Conclusion. Women with UPSC have a good prognosis when surgical staging confirms that disease is confined to the uterus (Stage I/II). Surgical findings can also be used to tailor adjuvant radiation treatments. Further study is required to define the optimal treatment for women with metastatic UPSC.

Objective To evaluate patterns of recurrence for ovarian, fallopian tube, and primary peritoneal cancer patients undergoing extended treatment with bevacizumab (BEV). Methods A retrospective review of patients with primary ovarian, fallopian tube, or peritoneal cancer treated with BEV alone or in combination with other chemotherapy from 2001 to 2011 was performed. Qualified patients were identified by chemotherapy records. Electronic medical records, labs, and imaging reports were reviewed and abstracted. Results Of 108 patients identified, 89 patients met study criteria by having disease progression either during treatment with BEV or after discontinuing BEV without initiating any other treatment. Patients on extended BEV therapy (>12 cycles) were more likely to recur in extra-visceral sites (p=0.04), especially in lymph nodes (p=0.0002), and presented with fewer symptoms at time of recurrence (p=0.02), compared to patients who had received≤12 cycles. CA-125 becomes less reliable for the detection of recurrent disease with extended BEV therapy (p=0.03 for≤12 cycles vs. p=0.08 for >12 cycles). Radiology was superior to CA-125, symptom, and physical exam, in detecting recurrence with extended BEV therapy (all p Conclusions Extended treatment with BEV in ovarian, fallopian tube, and peritoneal cancers results in alterations in the patterns of recurrence. Radiologic imaging is more reliable than CA-125, symptoms, or physical exam, in identifying recurrent disease in patients undergoing BEV treatment. As novel targeted therapies continue to be employed, guidelines for gynecologic cancer surveillance must continue to be reexamined.

Uterine malignant mixed mesodermal tumors (MMMT) are highly malignant tumors containing both malignant glands and stroma, while adenosarcomas (AS) are less aggressive tumors composed of malignant stroma and benign glands. Immunohistochemistry was used to grade overexpression of p53 protein, HER-2/neu protein, epidermal growth factor receptor (EGFR), and Ki-67 antigen in both the glands and stroma of tissue from 20 women with MMMT and 6 women with AS. EGFR was overexpressed in 2 AS and 9 MMMT, and was more commonly found in the sarcomatous component than the carcinomatous component in MMMT (P = 0.03). p53 was not found in any AS samples and was strongly present in 6 MMMT samples with a random distribution between the malignant components. HER-2/neu protein was not overexpressed in any AS or primary MMMT. Ki-67 antigen, a marker of cell proliferation, was found at higher levels in MMMT than AS samples (P = 0.03) and high Ki-67 antigen expression correlated with a decreased survival in patients with MMMT (P = 0.004). Independent characterization of oncogene proteins in the malignant components of these heterogeneous tumors may provide insight into the histogenesis and behavior of these malignancies.

Objective: Our purpose was to evaluate the contribution of intraoperative radiation therapy in the management of recurrent cervical cancer. Study design: Twenty-two patients were treated with electron beam intraoperative radiation therapy for recurrent cervical cancers that were confined to the pelvis but were too extensive to be adequately treated by radical surgery alone. All patients underwent extensive surgical dissection for exposure and maximal tumor resection. Doses of intraoperative radiation therapy ranged from 14 to 27.8 Gy (median 22 Gy). Twelve patients received intraoperative radiation therapy to address gross residual disease, and 10 patients were treated for microscopically positive or close surgical margins. Results: The five-year disease-specific survival and local control rates were 43% and 48%, respectively. There were trends toward better local control and disease-specific survival in patients with microscopic residual disease compared with those with gross residual disease. Seven patients had peripheral neuropathy related to treatment, and four of these cases resolved. Conclusion: In carefully selected cases intraoperative radiation therapy contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall.

Uterine papillary serous carcinoma (UPSC) is a distinct histologic type of endometrial cancer which is associated with a high relapse rate and poor prognosis. Between 1983 and 1993, 50 patients with UPSC of the endometrium were surgically staged. Thirty-three patients had pure UPSC and 17 had UPSC admixed with other histologies. Extrauterine disease was found in 36 women (72%). Lymph node metastases were present in 36% of women without myometrial invasion, 50% with inner one-half invasion, and 40% with outer one-half invasion. Similarly, the presence of intraperitoneal disease or positive washings did not correlate with increasing myometrial invasion. Grade and histology (mixed vs pure) were also not predictive of extrauterine disease. Patients with lymphatic/vascular space invasion (LVSI) were more likely to have extrauterine disease (85%); however, even without LVSI the incidence of extrauterine disease was 58% (P = 0.05). Unlike endometrioid adenocarcinomas, grade and depth of myometrial invasion were not significant predictors for extrauterine disease. This study reinforces the need for complete surgical staging in all patients with UPSC regardless of depth of invasion.

Objective : Our aim was to determine the efficacy and toxicity of paclitaxel in the treatment of refractory and platinum-resistant epithelial ovarian cancer. Study Design : Eligibility required three prior failed chemotherapy regimens and documented platinum resistance. One hundred patients with advanced ovarian cancer received paclitaxel 135 mg/m 2 over 24 hours every 21 days with optional granulocyte colony-stimulating factor support. Results : Paclitaxel was generally well tolerated. In four patients bowel perforation or fistula developed. After three cycles 34% of patients had stable disease and 25% of patients demonstrated a response, either partial or complete. After six cycles 24% of patients continued to respond. To date six patients have achieved a complete response. Conclusion : A 25% response rate in patients with refractory ovarian cancer was observed which was durable to six cycles.

Objective: Much debate exists on the initiation of chemotherapy for women at risk for persistent gestational trophoblastic disease. This is a result of a lack of early Predictors for the development of persistent gestational troPhoblastic disease after evacuation of a complete hydatidiform mole because the only current reliable method of detection and diagnosis lies in persistent or rising Postmolar R-human chorionic 9onadotroPin values. We used immunocytochemical techniques to retrospectively study the expression of the c- erb B-2 onco9ene product in formalin-fixed, paraffin-embedded troPhoblastic tissues as a potential indicator of the development of persistent gestational trophoblastic disease. Study Design: In this retrospective study 56 trophoblastic tumors were examined b means of immunocytochemical techniques to stain for the onco9ene product for evidence of c- erb B-2 expression. Our 56 cases included original tissue from 20 cases of complete mole that progressed to persistent gestational trophoblastic disease, seven cases of choriocarcinoma after term pregnancy or abortion and 29 cases of hYdatidiform mole representing Postevacuation, spontaneously regressing disease (including one partial mole). We also studied 11 cases of first-trimester trophoblast and 15 cases of term placenta as additional controls. Results: Our results showed positive immunostainin9 for c- erb B-2 gene product in one case of persistent gestational troPhoblastic disease, with negative staining in all other cases in the study groups and controls. Conclusion: Analysis for the significance of c- erb B-2 expression in persistent gestational trophoblastic disease showed that this correlation between c-erb B-2 expression and persistent gestational troPhoblastic disease is not significant, suggesting that future efforts should be directed at the involvement of different oncoproteins.

Objective:To compare the survival of patients with bilateral versus unilateral malignant ovarian germ cell tumors (OGCT).Methods:Patients with a diagnosis of OGCT were identified from the Surveillance, Epidemiology, and End Results Program for the period 1988 to 2006 and were divided into bilateral and unilateral subgroups. Only surgically treated patients were included. Histologic types were grouped into dysgerminoma, malignant teratoma, and mixed germ cell tumors with pure nondysgerminoma cell tumors. Statistical analysis using Wilcoxon rank sum test, Kaplan-Meier survival methods, and Cox proportional hazards regression model were performed.Results:In 1529 patients with OGCT, 1463 (95.7%) were unilateral and 66 (4.3%) were bilateral. Bilaterality was more common with dysgerminomas (6.5%) and mixed germ cell tumors with pure nondysgerminoma cell tumors (6.25%) than with immature teratomas (1.7%),P< 0.001. Most OGCT (67.3%) were stage I. Bilateral OGCT were more likely than unilateral tumors to be associated with advanced-stage disease (FIGO III and IV, 41% vs 20%,P< 0.04). Overall 5-year survival was 93.6% for unilateral OGCT and 80.7% in bilateral OGCT,P< 0.001. In multivariate analysis, bilaterality was not an independent predictor of survival when controlling for age, histology, stage, and surgical staging (hazard ratio, 1.3; 95% confidence interval, 0.7-2.5;P= 0.40).Conclusions:Compared with unilateral tumors, bilateral OGCT are more often associated with advanced-stage disease, high-risk histology, and poor survival. When other prognostic factors are accounted for, bilaterality was not an independent prognostic predictor of survival.

Purpose : To determine, in a retrospective single institutional study, the role of concurrent radiotherapy and chemotherapy in the treatment of local-regionally advanced vulvar cancer. Methods and Materials : From 1984 to 1991, 20 patients with locally extensive primary or recurrent carcinoma of the vulva were treated with initial combined radiotherapy and chemotherapy. Seven patients had Federation Internationale de Gynecologie et d'Obstretrique Stage III disease, 10 had Stage IV disease, and three were treated for recurrent disease. None of these patients were considered candidates for primary radical vulvectomy and groin node dissection. Median radiation doses to regions of microscopic disease and gross tumor were 40 Gy (range 30–54 Gy) and 54 Gy (34–70.4 Gy), respectively. All patients received 2 or 3 cycles of 5-Fluorouracil concurrently with radiotherapy. In addition, five patients received Cis-platinum, and one Mitomycin-C. Median at-risk follow-up interval was 37 months. Results : Ten patients had complete resolution of tumor to initial chemoradiotherapy, and eight of these have remained free of tumor relapse. Eight other patients had partial responses, with tumor bulk reduced by > 50%, while the remaining two patients had local-regionally progressive disease. Six of the patients with partial responses had residual tumor successfully resected, although four subsequently recurred. For the entire group of 20 patients, the actuarial 3- and 5-year local control rates were 48% each, and the corresponding disease-specific survival rates were 59% and 49%. There was a suggestion that better local control was obtained in patients who received gross tumor radiation doses ≥ 50 Gy. Skin reaction was the major acute toxicity and responded well to conservative management. Long-term sequalae were limited to skin and subcutaneous atrophy. Conclusion : These results indicate that initial combined radiotherapy and chemotherapy is effective in the management of advanced vulvar cancer.

Objective GOG 172 showed a survival benefit with intraperitoneal (IP) cisplatin for advanced ovarian cancer, but patients tolerated the regimen poorly. We hypothesized that women treated with alternative IP chemotherapy strategies may have less toxicity and improved compliance. Methods We reviewed the records of women with ovarian cancer and optimal surgical debulking who underwent IP chemotherapy at our institution. Primary outcomes analyzed were completion rates and toxicities of IP chemotherapy. Secondary outcomes were progression-free and overall survival. Statistical analysis was performed using STATA 10.0. Results Thirty-nine patients with primary ovarian or peritoneal cancer who underwent IP chemotherapy were identified over a 2 year period. Patients were treated with IV paclitaxel followed by IP cisplatin (64%) or IP carboplatin (36%). Median two cycles of intravenous (IV) taxane and carboplatin were given prior to initiating IP therapy in 77% of patients. Median number of IP chemotherapy cycles was 5 and median total number of cycles was 8. Seventy-four percent (74%) of patients received four or greater cycles of IP chemotherapy. There was a higher rate of completion of intended number of IP cycles in the carboplatin group (92%) versus 60% in the IP cisplatin group ( p =0.05). Grade 3 non-hematologic toxicities were more common in the IP cisplatin group than in the IP carboplatin group (24% and 0%, p =0.046). At median follow-up of 24 months, the median progression-free interval and overall survival have not yet been reached for either group. Conclusion Intraperitoneal chemotherapy regimens using carboplatin or cisplatin and dropping day 8 IP paclitaxel have less toxicity and less discontinuation of therapy.

Apart from choriocarcinoma, involvement of the central nervous system (CNS) by gynecologic malignancy is rare. A 10-year retrospective review at the University of Washington Medical Center (Seattle, WA) and Swedish Hospital and Medical Center Tumor Registry (Seattle, WA) identified 14 patients with cerebral metastases from ovarian carcinoma. Median age at diagnosis of cerebral metastases was 52.5 years. Median interval from the diagnosis of ovarian carcinoma to the diagnosis of CNS metastases was 14.5 months. Seven patients had received cisplatin therapy before CNS relapse. Seven patients underwent second-look procedures before developing CNS metastases; in three, results were negative. Eight patients had evidence of extraperitoneal spread to other sites at the time of CNS relapse. Clinical manifestations included motor weakness, seizures, headache, confusion, and speech disturbance. All lesions were contrast enhancing on computed tomography (CT) scans and were located in the cerebral hemispheres. Nine patients had single lesions, five of whom underwent surgical resection of the lesion with histologic confirmation of metastases from the primary site. Median survival was 2 months in patients receiving radiation therapy alone and 17 months in patients who received surgery and radiation. Median survival of the entire series was 3 months. The presence of multiple cerebral metastases or evidence of extraperitoneal spread elsewhere in the body was adversely associated with survival. The prognosis of patients with cerebral metastases from ovarian carcinoma appears poor. However, early diagnosis by routine CT scanning followed by surgical resection and radiation may improve overall survival in a select group of patients.

Objective. Define the maximum tolerated dose of weekly gemcitabine given concomitantly with standard weekly cisplatin and pelvic radiotherapy for primary treatment of cervical cancer. Methods. Gemcitabine at specified dose levels was given concomitantly with weekly cisplatin at 40 mg/m 2 for six cycles with concurrent radiotherapy in primary therapy of stage IB–IVA cervix cancer. Radiation consisted of 4500–5000 cGy in 25 daily fractions combined with brachytherapy to take point A to ≥8500 cGy. Results. At gemcitabine 100 mg/m 2 , three of six patients demonstrated a dose limiting toxicity (DLT). At gemcitabine 50 mg/m 2 , two of two had DLTs. DLTs consisted of severe fatigue, lymphopenia, diarrhea, and tinnitus. All patients had a clinical complete response; four pathologically confirmed. Two patients recurred outside the radiated field and seven are disease-free (median follow-up 30 months). Following the second DLT at gemcitabine 50 mg/m 2 , the trial was stopped according to predetermined criteria. Conclusions. Adding low dose weekly gemcitabine to cisplatin and pelvic radiotherapy resulted in an excellent response but unacceptable toxicities. Addition of gemcitabine prior to weekly cisplatin with radiation for cervical cancer will likely require reduction of cisplatin doses.

To evaluate the effect of body mass index (BMI) on clinical/pathologic features, surgical morbidity, and outcome in patients with endometrial cancer.All women with surgically treated endometrial cancer at the University of Washington in Seattle, Washington, between 1 January 1990 and 1 January 2000 were eligible; 439 patients were identified and 43 were excluded due to incomplete medical records; 396 patients underwent retrospective chart review. Statistical analysis was performed by SPSS. Median follow-up time was 27 months (range, 1 to 120 mo).Mean BMI was 34 (range, 15 to 69). BMI was30 in 40.7% of patients, 30 to 40 in 32.3%, and40 in 27.0%. Clinically, patients with a BMI of40 were more likely to have hypertension, diabetes, and pulmonary disease. Those patients with a BMI of40 had statistically longer operating times (209 vs. 159 min) and more blood loss (604 vs. 324 ml) than patients with a BMI of30. However, there was no difference between the three groups in number of lymph nodes removed, units of blood transfused, length of hospital stay, number of intensive care unit (ICU) days, or intraoperative complications. Postoperatively, patients with a BMI of40 were more likely to have a wound separation than thinner patients. Pathologically, patients with a BMI of40 were more likely to have endometrioid histology, lower stage disease, and lower grade tumors than women with a BMI of30. However, 11.3% of patients with lymph node sampling and a BMI of40 had positive lymph nodes and 23% were stage II or higher. Forty-two patients (10.6%) recurred. There were no postoperative deaths, and there was no difference in survival between the three groups.Patients with a BMI of40 frequently have favorable stage I endometrial cancers. However, approximately a quarter of these patients have evidence of cervical or extrauterine disease. This study confirms that surgical staging can be performed adequately and safely in morbidly obese patients with no difference in length of hospital stay, number of ICU days, intraoperative or postoperative complications.

Paclitaxel is currently being utilized to treat neoplasms which have a significant incidence of central nervous system metastases. It is, however, unclear as to whether paclitaxel crosses the blood-brain barrier. In this report, the authors describe a patient with refractory epithelial ovarian cancer treated with paclitaxel at 135 mg/m2/24 hr every 21 days. The patient achieved a complete clinical response of all abdominal and pelvic disease, but simultaneously developed central nervous system metastases. Paclitaxel was effective against the patient's abdominal and pelvic disease but was not protective against central nervous system metastasis.

Vulvar and vaginal cancer precursor lesions are predominantly squamous cell neoplasias that contain HPV DNA. Other risk factors that are similar to CIN include current smoking, a history of prior genital warts or anogenital neoplasia, and multiple sexual partners. Unlike cervical cancer, vulvar and vaginal neoplasias are rare, and prevention beyond visual examination is not a part of routine gynecologic care. Women with impaired immunity (e.g., organ transplant recipients, acquired immunodefi- ciency syndrome patients, and patients who are treated with corticosteroids) should be screened periodically. A history of previous HPV-related diseases should be obtained in these women before determining the frequency of cytologic screening.

Objective. The aim of this study was to evaluate the impact of surgical staging in the treatment and outcome of women with locally advanced cervical cancer. Methods. Ninety-eight women with locally advanced cervical cancer treated between 1993 and 1997 were retrospectively reviewed. Survival probabilities were calculated by the Kaplan–Meier product limit method and compared with the log-rank test. Results. Of the 98 women treated over the 5-year period, 86 were surgically staged: 61 by a retroperitoneal approach, 18 by laparoscopy, and 7 by laparotomy. Median blood loss was 120 cc and median length of hospitalization was 3 days. Preoperative CT scans ( n = 55), when compared with surgical findings, missed macroscopic nodal disease in 20% and microscopic disease in 15% and overcalled disease in 10% of cases. Lymph node metastases were found in 45/86 patients (52%): 12 microscopic and 33 macroscopic. The highest level of nodes found to be involved was pelvic in 23, common iliac nodes in 3, para-aortic nodes in 14, and scalene nodes in 5 cases. Of the 86 patients, 49 received pelvic radiation, 27 received extended field radiation, and 10 were identified for palliative treatment only (5 scalene node metastasis, 5 extensive intraperitoneal disease). For node-negative patients, 5-year survival was 74%; for microscopic nodal involvement it was 58%; and for macroscopic involvement it was 39% ( P = 0.007). Five-year survival for women with para-aortic node involvement was 52%. Number of nodes involved was a significant prognostic variable ( P = 0.008). Patients who received chemotherapy had a 5-year survival of 68% compared to 35% for those who did not ( P = 0.06). Factors which did not affect survival included age, histology, type of surgery, stage, and type of radiation (pelvic vs extended). Conclusion. Surgical staging of women with locally advanced cervical cancer can be performed with acceptable morbidity and it provided more accurate information than CT scans and resulted in a modification of the standard pelvic radiation field for 43% of our patients. The information obtained from surgical staging allows better individualization of therapy, which may improve overall clinical outcome.

The Syed template (Alpha-Omega Services, Bellflower, CA) has been established as an advance in interstitial gynecologic brachytherapy. Unfortunately, enthusiasm for the technique is often tempered by certain tumor geometries which require blind insertion of the interstitial needles, potentially risking inaccurate placement of the radioactive sources and viscus perforation. These concerns arise particularly in the management of anterior vaginal tumors where difficulties in negotiating the pubic arch can prevent optimal needle placement. In answer to this problem, a technique utilizing an open retropubic approach for Syed template interstitial implants in anterior vaginal tumors under direct visualization is described. To date, six procedures have been performed. The disease entities include advanced cervical squamous cell carcinoma, clear cell carcinoma of the vagina, recurrent vaginal carcinoma, recurrent endometrial carcinoma, and urethral adenocarcinoma. Complete response was noted in five of six patients but persistent local control of disease was achieved in only one of five complete responses over a relatively short follow-up interval. Complications included paravaginal abscess (n = 1), postoperative deep venous thrombosis (n = 1), abdominal incision cellulitis (n = 1), and radiation enteritis (n = 1). An open retropubic approach allows direct visualization of the bladder and urethra during interstitial implantation of anterior vaginal malignancies and facilitates negotiation of the pubic arch. In our experience, this technique results in improved needle positioning and is thus intuitively likely to aid in avoiding injury to surrounding normal tissues. Additional accrual of a larger cohort will be necessary to arrive at any meaningful objective conclusions regarding the technique's benefit over current modalities.

Seven patients with gastrointestinal necrosis following paclitaxel chemotherapy are reported. Four of seven patients had platinum refractory disease, while 3/7 patients received primary paclitaxel therapy. Complications occurred 5 to 16 days following paclitaxel therapy. The most common clinical presentation was fever (7/7 patients), neutropenia (6/7 patients), and abdominal pain (6/7 patients). All seven patients developed gastrointestinal necrosis following the first cycle of paclitaxel chemotherapy. The exact mechanism by which this complication occurs is poorly understood. We postulate that gastrointestinal necrosis may be the result of a direct drug effect on the gastrointestinal epithelium and might involve a synergistic interaction between compromised bowel and paclitaxel-induced mitotic arrest. We observe that the incidence of gastrointestinal necrosis in patients with platinum refractory disease is 4 of 108 patients (3.7%). The incidence of this complication in patients receiving primary paclitaxel at our institution is 3 of approximately 128 patients (2.3%). Eighteen cases to date have been identified in the literature. A high index of suspicion of this complication should be considered for patients presenting with neutropenic fever and abdominal pain following paclitaxel chemotherapy.

Objective. To determine if immunoreactive inhibin assayed in serum from women with granulosa cell tumors correlated with tumor burden, reflected response to treatment, or predicted recurrent disease. Study design. Serum samples were collected following bilateral oophorectomy (BSO) with or without other indicated surgery in 15 patients with granulosa cell tumors. Inhibin radioimmunoassay (RIA-Inh) was performed on all samples and results were correlated with tumor burden, disease status, and treatment response. Results. Fifteen patients had serum assayed for inhibin with levels ranging from 0 to 7470 U/liter. In 4 patients with measurable recurrent disease, inhibin levels correlated directly with tumor burden ( r 2 = 0.96). Four patients had serum drawn during clinical remission and in all 4 patients elevated inhibin levels predated recurrence by a median interval of 11.5 months (range 7–20). The remaining 7 were treated for primary disease and were in clinical remission with a median follow-up of 33 months (range 9–53). Four of these 7 patients were surgically staged: 2 were FIGO Stage I and inhibin levels fell to 0 U/liter; 2 patients had metastatic disease (Stage IIc and IIIa) and their inhibin levels were found to be elevated following complete resection. The remaining 3 were not surgically staged, and all had elevated inhibin levels while in clinical remission, suggesting occult disease. Of the 15 total patients, 1 who was treated with chemotherapy for recurrent disease was followed with serial inhibin levels. She showed a complete response to therapy with inhibin levels falling from 975 to 0 U/liter with 15 months follow-up. Conclusions. Serum inhibin levels reflect tumor burden and may be valuable in assessing response to chemotherapy or predicting recurrent disease in women with granulosa cell tumors who have had BSO. Serum inhibin level evaluation should be incorporated into large-group trials of therapy for granulosa cell tumors.

OBJECTIVES: A phase II trial of high-dose cyclophosphamide, etoposide, and cisplatin was done. STUDY DESIGN: Forty-eight patients with progressive or persistent disease and previous cisplatin-based chemotherapy and no paclitaxel therapy were entered for treatment on the basis of two cycles of cyclophosphamide (4500 mg/m 2 ), etoposide (750 mg/m 2 ), and cisplatin (120 mg/m 2 ). RESULT: Seventy-four cycles were delivered. Six patients died during treatment (12.5%). Of 28 with measurable disease, there was a 25% response rate and 32% had stable disease. Median time to recurrence and survival were significantly different for minimal versus bulky disease ( p = 0.0089, p = 0.0008, log-rank) and for platinum-sensitive versus platinum-resistant disease ( p = 0.18, p = 0.0012, log-rank). The number of prior regimens was not correlated with time to progression or survival. CONCLUSION: This study shows little advantage for high-dose protocols except for patients with a response to platinating agents and minimal residual disease. (Am J Obstet Gynecol 1996;174:1688-94.)

Between 1982 and 1992, 24 women with Stage III clear cell ovarian cancer were identified from the tumor registry. Thirty-four women with Stage III papillary serous tumors treated between 1987 and 1989 were used as a comparison. All patients underwent cytoreductive surgery followed by conventional platinum-based chemotherapy. In the women with clear cell histology, nine (37.5%) had endometriosis in the surgical specimen compared with one (3%) in the papillary serous group (P = 0.002). Ten women (42%) with clear cell histology experienced a thromboembolic event during the course of treatment, compared to six (18%) in the papillary serous group (P = 0.05). In the group with clear cell histology, overall, 70% of women had progressive disease. Fifty-two percent experienced clinical progression while receiving platinum-based chemotherapy. In addition, four patients were found to have progressive disease at second-look laparotomy. Only two patients had a pathologic complete response. In the group with papillary serous histology, 29% overall had progressive disease while on chemotherapy (P = 0.005). The median survival for the women with clear cell histology was 12 months compared to 22 months for those with papillary serous (P = 0.02). For women with clear cell histology, univariate analysis was used to evaluate prognostic factors. Age less than 50 was a poor prognostic factor (P = 0.045). The presence of endometriosis, thromboembolic event, or optimal cytoreduction were not prognostic factors (P = 0.67, P = 0.34, P = 0.39). Patients with advanced clear cell ovarian cancer have a poor response to conventional platinum-based chemotherapy and overall prognosis is poor.

The purpose of the study was to evaluate the utility of immunocytochemistry in the management of cervical adenocarcinoma. Patterns of reactivity to various immunocytochemical markers were correlated with clinically known risk factors for recurrence.A retrospective evaluation of 55 patients with invasive cervical adenocarcinoma was conducted. Monoclonal antibodies were generated against various human intermediate filament proteins and tested on fixed, paraffin-embedded tissue by the avidin-biotin complex immunoperoxidase method. Dako V9 antivimentin antibodies and two anticytokeratin antibodies, 35 beta H11 and 34 beta E12, were used. Polyclonal antibodies to carcinoembryonic antigen and antibodies to epithelial membrane antigen were used.Of 55 patients, 50 (91%) had positive epithelial membrane antigen antibodies in tumor cells. Tissue from patients with cervical adenocarcinoma demonstrated positivity for 35 beta H11 antibodies in 46 of 53 patients (87%) and positivity for 34 beta E12 antibodies in 15 of 54 patients (28%). Vimentin antibodies were negative in all except one patient. Carcinoembryonic antigen-positive antibodies were detected in 37 of 55 patients (67%). This study also demonstrated consistent negative expression of vimentin in invasive cervical adenocarcinoma. Carcinoembryonic antigen expression rates were 50% and 75% for patients with small tumors (less than or equal to 2 cm) and large tumors (greater than 2 cm), respectively (p less than 0.01). Patients with carcinoembryonic antigen expression are at increased risk for recurrence and also sustain reduced survival potential.Patients with cervical adenocarcinoma and carcinoembryonic antigen expression are at increased risk for recurrence. We speculate that immunocytochemistry may detect lymph node micrometastases otherwise unsuspected by conventional microscopy.

The incidence of bone marrow involvement with epithelial ovarian cancer has been evaluated as a continuation of interest in autologous bone marrow support. Fifty-eight aspirates were obtained on 50 patients and 53 aspirates were evaluable. Immunocytochemistry with the monoclonal cytokeratin antibodies 35 beta H11 and 34 beta E12 was performed. There have been no complications. Twelve (23%) were positive and three were indeterminate. Stage, grade, and CA-125 level were not different in the two groups. No patient had a positive biopsy at the time of initial diagnosis. The majority of patients were drawn from second-look procedures; of these, 7 of 19 were positive. Five of twelve with positive aspirates died from disease versus 5 of 38 with negative aspirates, and patients with a positive aspirate had a longer overall survival time until death from disease. We can confirm the presence of epithelial ovarian cancer in 23% of patients at varying times in the course of their disease. We cannot identify risk factors for the development of this finding nor the viability of those cells when found in this data set.

The International Federation of Gynecology and Obstetrics instituted a change in the classification for carcinoma of the cervix with a new substage IA 2 . The criteria for this substage exceed the generally accepted criteria for microinvasion. Fifty patients with early invasive squamous cell carcinoma of the cervix were treated from 1976 through 1983 with a cone biopsy followed by a radical hysterectomy and pelvic lymph node dissection. These patients were reviewed to evaluate the ability to make the histologic diagnosis and to examine the natural history of the disease with maximal treatment. Histologically positive margins were found at the time of cone biopsy in 66% (33/50) of the patients. Negative margins at the time of cone biopsy were identified in 34% (17/50) of the patients. Residual invasive disease at the time of radical hysterectomy was found in 24% (4/17) of the patients with negative margins. Two of the 50 patients had positive lymph nodes. Three patients had recurrent metastatic disease. This study demonstrates that a preoperative diagnosis of stage IA 2 invasive squamous cell carcinoma of the cervix is a difficult diagnosis to establish and creates a therapeutic dilemma regarding treatment.

An upper abdominal midline incision was used for pelvic surgery in 16 morbidly obese patients (229-401 lb). When this approach is used, a Bookwalter retractor displaces the incision inferiorly and compresses the abdominal wall over the pelvis, and is then secured to the operating-room table. This approach provides adequate exposure of the pelvic organs and avoids an incision in the panniculus with its associated complications. No wound infections, postoperative dehiscences, or other serious postoperative morbidity occurred in these patients.

Whole-pelvis radiation therapy has been traditionally delivered through fields, the dimensions of which have been determined by convention and based largely on textbook anatomic landmarks. Since July 1986, 100 patients have had intraoperative retroperitoneal measurements carried out at the time of radical surgery in an effort to examine this anatomic basis for field dimensions. Structural measurements of the pelvic and paraaortic arterial branches were made in reference to the lumbosacral prominence to correlate with lymphatic pathways. The mean level of the aortic bifurcation was found to be 6.7 cm above the lumbosacral prominence. The mean level of the bifurcation of the common iliac artery was 1.7 cm above this reference point on the right and 1.4 cm above on the left. Both common iliac bifurcations were cephalad to the level of the lumbosacral prominence in 87% of patients. In only three patients were both bifurcations located below this level. Transverse pelvic dimension measurements demonstrated a width of 12.3 cm at the level of the obturator fossa and of 13.0 cm at the most inferior outside width of the external iliac arteries. To establish a simple external reference which could assist in defining radiotherapy field widths, the maximal separation of the femoral arteries at the level of inguinal ligaments was measured and averaged 14.6 cm. These data suggest that conventional fields frequently fail to correspond to true anatomic landmarks and that to optimally cover the lymphatics in radiotherapy, fields should, ideally, be based on intraoperative measurements. If such surgical guides are not available, we would suggest that standard whole-pelvis radiotherapy for cervical cancers should employ anterior and posterior fields with widths of at least 16 cm which will fully include the bifemoral separation. A superior border at the L4-L5 interspace is required to cover lymphatic pathways to the mid-common iliac nodal level. It may also be convincingly pointed out that the attachments of the uterosacral and cardinal ligaments are clearly posterior to the rectosigmoid, mandating lateral fields that shouid encompass the entire anterior sacral silhouette.

The International Federation of Gynecology and Obstetrics instituted a change in the classification for carcinoma of the cervix with a new substage IA 2 . The criteria for this substage exceed the generally accepted criteria for microinvasion. Fifty patients with early invasive squamous cell carcinoma of the cervix were treated from 1976 through 1983 with a cone biopsy followed by a radical hysterectomy and pelvic lymph node dissection. These patients were reviewed to evaluate the ability to make the histologic diagnosis and to examine the natural history of the disease with maximal treatment. Histologically positive margins were found at the time of cone biopsy in 66% (33/50) of the patients. Negative margins at the time of cone biopsy were identified in 34% (17/50) of the patients. Residual invasive disease at the time of radical hysterectomy was found in 24% (4/17) of the patients with negative margins. Two of the 50 patients had positive lymph nodes. Three patients had recurrent metastatic disease. This study demonstrates that a preoperative diagnosis of stage IA 2 invasive squamous cell carcinoma of the cervix is a difficult diagnosis to establish and creates a therapeutic dilemma regarding treatment.

This study was undertaken to evaluate the morbidity and potential benefits of concurrent gracilis myocutaneous graft with exenteration. All patients undergoing exenteration from 1962-1986 were reviewed, of whom 24 had concurrent grafts. The mean operative time, blood loss, and hospital stay were not different in patients with versus without grafts. The rate of fistula formation in the hospital was less in the graft group (P = .004) but was not different when compared with contemporary patients only. The total infection rate (wound and pelvic) was decreased in the graft group (P = .04) when graft infections were excluded. The major problem with the graft was significant necrosis of the flap(s) in nine of the 24 patients. There were no life-threatening complications attributed to concurrent placement of gracilis myocutaneous flaps. Experience with the technique is improving the cosmetic and functional outcome of the neovagina formed with the graft. Patients most likely to benefit from this procedure include those requiring immediate reconstruction or those with potentially poor healing due to high-dose pelvic radiation, including intraoperative radiation.

The timing of treatment for stage I-B cervical carcinoma diagnosed during pregnancy is complicated by conflicting concerns for fetal survival and control of malignancy. There were 11 pregnant women with stage I-B cervical carcinoma diagnosed prior to fetal viability since 1969. Six patients were managed with termination of pregnancy and radical hysterectomy with pelvic lymphadenectomy. In 5 patients, treatment was delayed for 6 to 17 weeks and then delivery was accomplished by cesarean section followed directly by radical hysterectomy and pelvic lymphadenectomy. Two of the infants experienced complicated neonatal courses and would have benefited from additional delay. Benefits that could be achieved by delaying delivery for the fetus were calculated from a review of 600 inborn infants without congenital anomalies admitted to the neonatal intensive care (NICU) during 1984 and 1985. Neonatal mortality decreased from 32.8% at 26–27 weeks to 2.7% at 34–35 weeks gestation. Similar improvements in neonatal morbidity were demonstrated. Although adverse maternal outcomes were not associated with delay, an evaluation of risk cannot be derived from this series. Significant fetal benefit can accrue from relatively short delays in planned delivery dates. When stage I-B cervical carcinoma is diagnosed during pregnancy and when fetal survival is desired, delivery should be delayed to achieve fetal maturity, rather than only potential viability.

One hundred eighty-six radical abdominal hysterectomies are reviewed. Twenty-two instances of clinically recurrent carcinoma following operation were encountered over an 18-year period. In review of these cases it is apparent that patients with adenocarcinoma or adenocystic carcinoma have an increased likelihood of positive lymph node metastases or lymphatic-vascular invasion at the time of surgery. If this occurs, there is an increased probability of recurrent disease. Poor differentiation of the tumor, bulky disease, deep infiltration of tumor, involvement of capillary-like spaces, and lymph node metastases all appear to represent poor prognostic indices in patients operated upon. Patients with adenocarcinoma generally have a longer disease-free interval before recurrence than patients with squamous carcinoma. Postoperative radiation therapy following radical surgery appears to increase significantly the disease-free interval until recurrence and influences the site of recurrent disease but has no demonstrable effect on ultimate survival.

Adenocarcinoma of the cervix represented 12.7% of all cervical carcinomas seen at the University of Washington. The mean age of 66 patients with adenocarinoma of the cervix was not significantly different from the mean age of those with squamous cell carcinoma and was 43.6 (range 15–83). Seventy-six percent of the patients were assigned to Stage I disease. Stage II disease was diagnosed in 15% and Stages III–IV represented 9%. The pathologic diagnosis included adenocarcinoma in 50 patients, adenosquamous carcinoma in 9, clear cell carcinoma in 5, and adenoid cystic carcinoma in 2. The survival rate was directly related to the stage of disease and to the presence or absence of lymph node metastasis. The recurrence rate was significantly higher in adenocarcinoma of the cervix with node metastasis when compared with a similar group of patients with squamous cell carcinoma.

A study of 153 patients with squamous cell carcinoma of the vulva is reviewed. Regional node metastases were present in 20%, and lymphatic spread proved the single most significant prognostic factor in this disease. Recurrent carcinoma developed in 47% of cases with nodal metastases. Lymph node metastases were directly related to stage of disease, tumor differentiation, lesion size, and depth of invasion. Sixty percent of nodal disease was not suspected by clinical examination. No patient developing recurrent disease after identification of positive nodes survived the disease. Surgical staging based only upon size of lesion and presence of nodal metastases appears to offer a clearer prognostic profile than conventional clinical staging. The pattern and frequency of nodal spread suggest that in selected instances modifications of the standard surgical treatment of vulvar cancer may be appropriate.

A technique for high dose (5600-6100 cGy) extended field irradiation to the para-aortic lymph nodes is described. Fourteen patients have been treated with this technique, of whom 10 have had histologic confirmation of para-aortic node metastases. With follow-up ranging from 11 to 78 months, 7 of 14 patients are alive and clinically cancer-free. Acute effects of extended field treatment on patient weight and circulating blood counts are analyzed, and late treatment morbidity assessed. The findings suggest that such treatment, executed with modern equipment and appropriate technique, is not significantly more hazardous than pelvic irradiation, and can result in a substantial probability of disease-free survival.