The risk of hydrosalpinx formation and adnexectomy following tubal ligation and subsequent hysterectomy: a historical cohort study.

OBJECTIVE: The objective of the study was to further investigate a previous finding that tubal sterilization followed by hysterectomy was associated with hydrosalpinx formation. STUDY DESIGN: The Rochester Epidemiology Project (Rochester, MN) was used to identify three cohorts: women who had undergone tubal sterilization and subsequent hysterectomy, women who had undergone tubal sterilization alone, and women who had undergone hysterectomy alone. Four hundred seventy-three charts were reviewed and 337 met inclusion criteria. Patient histories were analyzed prospectively, looking for subsequent adnexal surgery. RESULTS: There was no increased risk of hydrosalpinx formation in patients who had undergone tubal sterilization and hysterectomy, compared with tubal sterilization alone. The proportion of subjects undergoing later adnexectomy for any reason was significantly higher in the hysterectomy groups, compared with the sterilization only group (relative risk 3.5, 95% confidence interval 1.3-9.4). CONCLUSION: This prospective study does not support the previously reported case-control data suggesting that tubal sterilization followed by hysterectomy resulted in an increased risk of hydrosalpinx formation, compared with tubal sterilization alone.

Long-term survival and disease recurrence in patients with primary squamous cell carcinoma of the vulva.

OBJECTIVES: To assess time to failure and sites of failure with extended follow-up of patients with squamous cell carcinoma (SCC) of the vulva. METHODS: A retrospective analysis of 330 patients with primary SCC of the vulva treated at Mayo Clinic between 1955 and 1990 was conducted. The main outcome measures were the rates of treatment failure. The Kaplan-Meier method and the log-rank test were used to estimate the rates of overall survival, disease-free survival, and recurrence. The Cox proportional hazards model was used to assess independent variables as prognostic factors for treatment failure. RESULTS: All 330 patients in the cohort underwent lymphadenectomy; 113 patients (34.2%) had involvement of the inguinofemoral nodes and 88 patients (26.7%) had treatment failure. Treatment failures occurred more frequently in patients who presented with inguinal metastasis at the primary surgery and during the first 2 years of follow-up. After 2 years, both groups, with or without positive inguinal nodes, had similar treatment failure rates. Most patients with disease recurrence in the groin died within the first 2 years of follow-up. Involvement of the inguinal nodes was the main independent predictive factor for survival, disease recurrence, and metastasis. CONCLUSIONS: Most treatment failures occurred during the 2 years after initial surgical management. However, in 35% of patients, disease reoccurred 5 years or more after diagnosis, which demonstrates the need for long-term follow-up. Complete ipsilateral or bilateral inguinofemoral lymph node dissection ensures a thorough evaluation and treatment of the groin.

Surgical treatment for local control of female urethral carcinoma.

We reviewed 53 patients (mean age 63 years) who underwent partial urethrectomy (n = 26) or radical extirpation (n = 27) for primary female urethral cancer from 1948 through 1999. Clinical stage, histology, high pathologic stage (3 or 4) and grade, tumor location, nodal status, surgery type, adjuvant therapy, and treatment decade were candidate outcome predictors. The predominant carcinomas were squamous cell (n = 21), transitional cell (TCC) (n = 15), and adenocarcinoma (n = 14). For adjuvant therapy, 20 patients had radiation (8 preoperatively), 2 had radiation + chemotherapy, and 1 had chemotherapy alone. During mean follow-up of 12.8 years, 27 patients had recurrence; 15 local only, 2 distant only and 10 local + distant. Of patients undergoing partial urethrectomy for pT1-3 tumors, 6/27 (22%) had urethral recurrence. Overall, there were no bladder recurrences. Recurrence-free survival +/- standard error (SE) at 10 years was 45 + 8%. Those who recurred had a cancer mortality rate of 71% at 5 years postrecurrence. The estimated 10-year cancer-specific survival (CSS) and crude survival (CS) rates were 60 +/- 8% and 42 +/- 7%, respectively. Pathologic stage was predictive for local recurrence (P = 0.02) and CSS (P = 0.01). Positive nodes on pathology were related to local and distant recurrence and CSS (P = 0.01). Upon review, partial urethrectomy resulted in a high urethral recurrence rate (22%) with no bladder recurrences. These patients may be better served with radical urethrectomy and creation of continent catheterizable stoma.

Carcinoid heart disease associated with primary ovarian carcinoid tumor.

Because the venous drainage of the ovary bypasses the portal circulation, carcinoid heart disease in patients with primary ovarian carcinoid tumors may develop in the absence of liver metastasis. We describe 4 patients who presented with symptomatic carcinoid heart disease in association with primary ovarian carcinoid tumor.

Endometrial carcinoma: paraaortic dissemination.

OBJECTIVE: The objective of our study was to identify pathologic factors predictive of tumor dissemination to paraaortic lymph nodes (LNs) in endometrial carcinoma. The identification of the risk factors may potentially facilitate selection of patients for radical surgery or radiotherapy directed to the paraaortic area (PAA). METHODS: The study population was a cohort from 612 consecutive patients with endometrial cancer surgically managed at our institution over a 10-year period. Tumor dissemination to the PAA was identified by selecting those patients who had either paraaortic LNs positive for disease at the time of primary surgery or those who subsequently experienced paraaortic failure or both (n=41; the "PA mets" subgroup). Therefore, patients for whom no information was available about the status of paraaortic LNs but who had received adjuvant irradiation to the PAA and those for whom information was not available about sites of recurrent disease were excluded from the analysis, leaving 566 patients to compose the study population. RESULTS: On the basis of univariate analysis, numerous pathologic variables were significantly (P< or =0.01) associated with PA mets. However, logistic regression analysis identified only two independent factors predictive of PA mets: positive pelvic LNs (P<0.001, OR=5.00) and lymphovascular invasion (LVI) (P=0.01, OR=1.99). Notably, only 2% of patients with negative pelvic LNs had PA mets compared with 47% of those with positive pelvic LNs (P<0.001). When both pelvic LNs and LVI were negative, only 0.8% of the patients had PA mets compared with 31% of patients for whom at least one of the two variables was positive (P<0.001). CONCLUSION: Positive pelvic LNs and LVI identify a subgroup of high-risk patients (approximately one sixth of the overall population) who potentially may benefit from formal lymphadenectomy or adjuvant therapy or both directed to the PAA. Furthermore, with 47% of patients with positive pelvic LNs having PA mets, unstaged patients at risk for pelvic LN involvement should be considered candidates for both pelvic and paraaortic external beam radiotherapy or surgical restaging.

Outcome of surgical treatment for primary malignant melanoma of the female urethra.

PURPOSE: We evaluate tumor characteristics, recurrence and survival following surgical treatment for female urethral melanoma. MATERIALS AND METHODS: A review of the records of all female patients with primary localized urethral melanoma (11, mean age 68 years) who underwent partial urethrectomy or radical extirpation from 1950 to 1999 was performed to determine disease specific survival and/or tumor characteristics correlating with survival. Clinical and pathological stage, tumor location, nodal status, adjuvant therapy and tumor pathological components including depth, width, necrosis and vascular/lymphatic invasion, were evaluated. Overall disease recurrence, crude and disease specific survival rates were calculated using the Kaplan-Meier method. RESULTS: Malignant melanoma occurred in the distal urethra in all 11 cases with local extension into the vagina (T3) in 7. Mean depth of invasion was 6.1 mm and mean tumor width was 2.0 cm. No vascular/lymphatic invasion or tumor necrosis was seen pathologically. No patient had received adjuvant therapy at the time of initial surgery. There were 7 recurrences (6 of 7 within 1 year postoperatively). Of the 7 cases of partial urethrectomy, urethral recurrence (1 with concurrent lung metastasis) developed in 5 and none had bladder recurrence. Those who underwent radical surgery had recurrence in the pelvis and lungs and inguinal lymph nodes. Crude and disease specific survival +/- standard error at 3 years was 27 +/- 15% and 38 +/- 19%, respectively. CONCLUSIONS: Primary female urethral melanoma is associated with a rapid and high local recurrence rate (60% at 1 year). Overall and cancer specific survival at 3 years is 27% and 38%, respectively. Local failure may in part be due to inadequate resection.

Cytokeratin staining of resected lymph nodes may improve the sensitivity of surgical staging for endometrial cancer.

OBJECTIVE: The presence of metastases to regional lymph nodes (LN) is the single most important risk factor in endometrial cancer. Advances in molecular biology have provided more sensitive methods for detecting micrometastasis. This was a pilot study to determine whether cytokeratin staining of LN from endometrial cancer patients is more sensitive than traditional histopathologic evaluation for the detection of micrometastasis. METHODS: The inclusion criteria included patients with surgical stage I-II endometrial cancer having >50% myometrial invasion, lesions >2 cm, and negative LN together with one of the following: FIGO grade 3 or cervical or lymph-vascular involvement. A matched control group included patients with LN metastasis. The evaluation of the LN at the time of initial surgery consisted of a frozen section and a reevaluation on permanent sections with H&E. In the study, lymphadenectomy specimens were cut, stained again with H&E and with cytokeratin, and examined. Cytokeratin staining was performed with AE1/AE3 antibodies. There were 16 LN-negative cases and 9 LN-positive controls. RESULTS: There was complete agreement between the LN assessment at time of surgery and the study H&E review prior to the staining for cytokeratin. However, 2 LN-negative cases (12.5%) had micrometastasis by cytokeratin staining. One of these patients developed recurrent disease in the para-aortic LN and died of disease at 2.8 years. CONCLUSION: Cytokeratin staining may improve the sensitivity for detection of metastasis compared to traditional evaluation. This study strongly suggests that these micrometastasis are clinically significant. An approach incorporating cytokeratin analysis could improve the risk assessment of specific patients.

Molecular and histopathologic predictors of distant failure in endometrial cancer.

A case-cohort study was designed to correlate various histopathologic and molecular variables with distant failure in endometrial cancer by analyzing phenotypic and molecular indices in hysterectomy specimens. From an overall population of 283 patients with endometrial cancer, we selected a cohort including all 49 patients who experienced any recurrence and 76 randomly chosen patients without recurrence. Expression of nuclear proliferating cell nuclear antigen (PCNA), MIB-1 (a marker of cell proliferation), and p53 was determined with digital image analysis, and cell membrane HER-2/neu and bcl-2 were quantitated visually. Ploidy and DNA indices were determined with flow cytometry. Overall, 6 immunohistochemical and 11 flow cytometric cases were eliminated because of technical inadequacies. Distant failures were defined as primary recurrences that developed outside the pelvis or vagina. Median follow-up was 91 months. Distant failures occurred in 13% of the patients. Cervical stromal invasion, positive adnexae, myometrial invasion >50%, positive lymph nodes, positive peritoneal cytology, lymphovascular invasion, grade 3 histology, nonendometrioid subtype, p53 >33%, strong HER-2/neu membranous staining, aneuploidy, S-phase fraction > or =9%, proliferative index > or =14%, and DNA index > or =1.5 significantly (P<0.05) predicted distant failures. However, a logistic regression model identified only p53 (OR=43.73; P<0.005), lymphovascular invasion (OR=11.59; P<0.001), and cervical stromal invasion (OR=11.29; P=0.001) as cogent predictors of distant failures. Only 3% of patients without any of these three predictors developed distant failures compared with 36% of those with at least one of the three (P<0.01). Thus, locoregional therapy may be insufficient when at least one of these predictors is present.

Distribution of estrogen receptors alpha and beta mRNA in mouse urogenital tissues and their expression after oophorectomy and estrogen replacement.

Estrogen receptors are present in the urogenital tract. However, little is known about the quantitative distribution of the traditional estrogen receptor (ERalpha) mRNA and the recently identified ERbeta mRNA. By quantitative reverse transcription polymerase chain reaction analysis, the distributions of ERalpha and ERbeta mRNA in mouse urogenital tissues and their expression in selected urogenital tissues after oophorectomy, with or without estrogen replacement, were evaluated. ERalpha mRNA concentrations were higher in the ovary, oviduct, uterus and vagina than in the kidney, ureter or bladder ( P<0.05); ERbeta transcripts were highest in the ovary, oviduct and bladder ( P<0.05). After oophorectomy and estrogen replacement, significant changes were identified in ERalpha and ERbeta mRNA expression. ERalpha and ERbeta mRNA are differentially expressed in mouse urogenital tissues. Oophorectomy and estrogen replacement affect estrogen receptors differently in the bladder, vagina and uterus. These results may explain some tissue-specific responses to estrogen and selective estrogen receptor modulators. The mRNA distributions of estrogen receptors alpha and beta and their expression after oophorectomy, with or without estrogen replacement, differ in mouse urogenital tissues.

Endometrial cancer: predictors of peritoneal failure.

OBJECTIVE: To assess determinants of peritoneal failure in endometrial cancer patients after definitive primary treatment. METHODS: Of 599 patients with endometrial cancer who had primary surgery at our institution during the decade before 1994, 131 had relapse. We defined "peritoneal failure" as relapse when it occurred in the upper abdomen or involved the pelvic peritoneum (or both). Mean follow-up was 72.8 months. RESULTS: Peritoneal failure was detected in 37 of 599 (6%) patients and represented 28% of identified failures. Stage IV disease, cervical stromal invasion, adnexal involvement, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, lymph node metastasis, histologic grade 3, nonendometrioid histologic subtype, absence of associated hyperplasia, and lymphovascular invasion correlated significantly (P < 0.01) with peritoneal failure. However, on regression analysis, only stage IV disease (P < 0.001, relative risk [RR] = 7.53), nonendometrioid histologic subtype (P = 0.02, RR = 3.01), and cervical stromal invasion (P = 0.04, RR = 2.83) were independent predictors of peritoneal failure. Because 22 of 37 (59%) peritoneal failures were in patients with stage IV disease, we considered separately the 545 patients with stage I-III disease. On regression analysis, nonendometrioid histologic subtype (P < 0.001, RR = 11.58), positive peritoneal cytology (P = 0.009, RR = 6.72), lymph node metastasis (P = 0.02, RR = 5.10), and cervical stromal invasion (P = 0.04, RR = 3.10) were independent predictors of peritoneal failure. Of the 38 patients in whom at least two of these four predictors were positive, 26% had peritoneal failure at 5 years, compared with 1% of the 507 patients who had none or only 1 predictor (P < 0.001). CONCLUSION: Patients with stage IV disease and those with stage I-III disease and at least two of the four independent predictors (nonendometrioid histology, positive peritoneal cytology, cervical stromal invasion, and lymph node metastasis) would be candidates for new therapeutic trials incorporating surgical and adjuvant treatment targeting the entire abdominal cavity.

Surgical stage I endometrial cancer: predictors of distant failure and death.

OBJECTIVES: The objective was to analyze the effect of various histopathologic characteristics on prognosis in surgical stage I (node-negative) endometrial carcinoma. METHODS: During a 10-year period, 229 patients with stage I epithelial (all subtypes) endometrial cancer had hysterectomy and node dissection. Mean number of nodes harvested was 16.2 pelvic and 5.7 paraaortic. Median follow-up was 83 months. Sixty-seven patients (29%) received adjuvant radiotherapy. RESULTS: Five-year disease-related survival (DRS) was 95%, and 5-year relapse-free survival (RFS) 91%. We observed 7 (3%) isolated vaginal recurrences, 14 (6%) distant failures, and 1 (0.4%) simultaneous recurrence at both regional (pelvic sidewall) and distant sites. Only 1 of 7 patients (14%) with vaginal failure died of the disease (median follow-up of censored patients after failure was 110 months), compared with 10 of the 15 patients (67%) with distant failure. By univariate analysis, myometrial invasion (MI) >or= 66%, nonendometrioid histology, lymphovascular invasion, absence of associated hyperplasia, and tumor diameter >2 cm were significant predictors of poor prognosis with distant failure (P or= 66% as the only independent predictor of DRS (P < 0.001, relative risk [RR] = 12.44), RFS (P < 0.001, RR = 8.67), and distant failure (P < 0.001, RR = 24.89). Only 2% of patients with MI < 66% had distant failure and died of the disease at 5 years, compared with a 29% 5-year distant failure rate and a 22% 5-year death rate among patients with MI >or= 66%. CONCLUSION: Stage I (negative nodes) endometrial cancer patients with MI >or= 66% are at significant risk for distant failure and death and should be considered candidates for new randomized trials of adjuvant systemic therapy.

Stage IIIC endometrioid corpus cancer includes distinct subgroups.

OBJECTIVE: Because stage IIIC corpus cancer is a heterogeneous substage, the outcomes of patients with stage IIIC disease were assessed according to the extent of extrauterine disease. METHODS: From 1984 through 1993, 51 patients with surgical stage IIIC corpus cancer were treated at our institution; 5 patients had tumors with nonendometrioid histologic features and were excluded from the analyses. Of the 46 patients with endometrioid carcinoma, 22 had lymph nodes as the only site of extrauterine disease (stage IIIC(0)) and 24 also had peritoneal cytologic, uterine serosal, adnexal, or vaginal involvement or a combination of these (stage IIIC(ab)). The mean number of lymph nodes removed was 18 pelvic and 8 aortic nodes. Median follow-up for surviving patients was 84 months. RESULTS: Patients with stage IIIC(0) cancer had a 5-year cause-specific survival (CSS) of 72% and a 5-year recurrence-free survival (RFS) of 68%, and those with stage IIIC(ab) had a CSS of 33% and an RFS of 25% (P < 0.01). Of the 22 patients with stage IIIC(0) endometrioid cancer, 21 had adjuvant radiotherapy (1 also received chemotherapy) and 1 was not treated. Relapse occurred in 7 (32%) patients, with only 1 having an initial failure component outside the node-bearing areas (lung). Of the 24 patients with stage IIIC(ab) cancer, 16 received adjuvant radiotherapy (1 had concomitant chemotherapy), 2 had chemotherapy, 4 had hormonal therapy, and 2 were not treated. We observed 16 recurrences (67%). Of the 14 patients with known initial sites of failure, 9 had an extranodal failure component. CONCLUSION: Assessment of CSS, RFS, and sites of relapse suggests that FIGO surgical stage IIIC endometrioid corpus cancer includes two distinct and readily separable subgroups: (1) stage IIIC(0), nodal involvement only, and (2) stage IIIC(ab), nodal plus cytologic, uterine serosal, adnexal, or vaginal involvement, or a combination of these. Our results also suggest that different treatment strategies are needed for these subgroups.

Factors that are associated with clinically overt postpartum urinary retention after vaginal delivery.

OBJECTIVE: This study was undertaken to determine the incidence of clinically overt postpartum urinary retention after vaginal delivery and to examine what maternal, fetal, and obstetric factors are associated with this problem. STUDY DESIGN: This was a retrospective case-controlled study of women who had overt postpartum urinary retention after vaginal delivery from August 1992 through April 2000. RESULTS: Fifty-one of 11,332 (0.45%) vaginal deliveries were complicated by clinically overt postpartum urinary retention. In most cases (80.4%), the problem had resolved before hospital dismissal. Persons with urinary retention were more likely than control subjects to be primiparous (66.7% vs 40.0%; P <.001), to have had an instrument-assisted delivery (47.1% vs 12.4%; P <.001), to have received regional analgesia (98.0% vs 68.8%; P <.001), and to have had a mediolateral episiotomy (39.2% vs 12.5%; P <.001). On multivariate logistic regression analysis, of these 4 variables, only instrument-assisted delivery and regional analgesia were significant independent risk factors. CONCLUSION: Clinically overt postpartum urinary retention complicates approximately 1 in 200 vaginal deliveries, with most resolving before hospital dismissal. Factors that are independently associated with its occurrence include instrument-assisted delivery and regional analgesia.

Laparoscopy versus laparotomy in the management of benign unilateral adnexal masses.

STUDY OBJECTIVE: To compare operative characteristics and charges of laparoscopy and laparotomy for women with a benign unilateral adnexal mass 7 cm or less in greatest diameter. DESIGN: Historical cohort study (Canadian Task Force classification II-2). SETTING: Clinic department of obstetrics and gynecology. PATIENTS: One hundred six women. INTERVENTION: Unilateral oophorectomy or unilateral salpingo-oophorectomy performed by laparoscopy or laparotomy. MEASUREMENTS AND MAIN RESULTS: When patients were compared on an intent to treat basis, no differences in greatest mass diameter (4.2 vs 4.5 cm), patient age (49.2 vs 46.4 yrs), or body mass index (26.0 vs 27.0 kg/m(2)) were found between 62 laparoscopies and 44 laparotomies. Laparoscopy was associated with longer operating times (94 vs 63 min, p <0.001), shorter hospital stay (1.6 vs 2.5 days, p <0.001), higher sterile supply charges ($1031 vs $40, p <0.001), and lower hospital room charges ($672 vs $1351, p <0.0001). No significant differences in total hospital charges, febrile morbidity, or transfusion rates were identified. CONCLUSION: Patient charges and early operative morbidity are similar for laparoscopy and laparotomy. Therefore, patient and surgeon preference should be a primary consideration when deciding on operative approach in carefully selected women with a unilateral adnexal mass.

Assessment of prognostic factors in stage IIIA endometrial cancer.

OBJECTIVE: The objective of this study was the assessment of prognostic factors in stage IIIA endometrial cancer. METHODS: Between 1984 and 1993, 51 patients with stage IIIA endometrial cancer received definitive treatment at our institution. Thirty-seven patients had positive peritoneal cytologic findings only (stage IIIA1), and 14 had adnexal or uterine serosal involvement (USI) (stage IIIA2). Median follow-up of surviving patients was 82.5 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 88 and 73%, respectively. RFS was 79% in patients with stage IIIA1 disease, compared with 57% in patients with stage IIIA2 disease (P = 0.04). However, DRS did not significantly differ between stages IIIA1 and IIIA2. In the 37 patients with stage IIIA1 tumors, histologic grade 3, nonendometrioid histologic subtype, and lymphovascular invasion (LVI) significantly predicted a poor prognosis, with extraabdominal sites of failure (P < 0.05). Of the 22 patients who had stage IIIA1 disease with endometrioid histologic subtype and without LVI, none had recurrence [17 had whole abdominal irradiation (WAR) or intraperitoneal injection of (32)P, 2 had pelvic external radiotherapy (PRT)]. By contrast, of the 15 patients with either nonendometrioid histologic subtype or LVI, 9 (60%) had recurrence and 7 (47%) died of disease (12 had WAR or (32)P). An extraabdominal component was present in 7 of the 9 recurrences observed in this subgroup. Among the 14 patients with stage IIIA2 tumors (6 had WAR, 6 had PRT), those with USI had a 5-year DRS of 83% and a rate of extraabdominal failure of 83%, compared with 100 and 12.5% in patients without USI (P < 0.05). CONCLUSION: Patients with stage IIIA endometrial cancer who have endometrioid tumors, no LVI, and positive peritoneal cytologic findings as the only sign of extrauterine disease have an excellent prognosis. Nonendometrioid histologic subtype, LVI, and USI are strong predictors of distant failures and poor prognosis. Patients with either of these histologic factors should be considered candidates for systemic adjuvant therapy.

Two cases of coincident carcinomas of the head and neck and the uterine cervix.

BACKGROUND: Human papillomavirus (HPV) is an independent risk factor for select head and neck carcinomas and most uterine cervix carcinomas. We report two patients with synchronous diagnoses of cervical cancer and HPV-related head and neck cancer. CASE: One patient was a 53-year-old woman with regionally metastatic tonsillar carcinoma treated surgically and with adjuvant radiation. Abnormal vaginal bleeding developed. Gynecologic examination showed advanced cervical carcinoma. The other patient was a 78-year-old woman surgically treated for carcinoma of the left anterior nose. Five months later, symptoms of recurrent nasal carcinoma and concurrent vaginal bleeding developed. Gynecologic examination showed advanced cervical carcinoma. CONCLUSIONS: These cases of coincident tumors demonstrate possible systemic susceptibility to the carcinogenic effects of HPV. The common association of HPV with both uterine cervix cancers and select head and neck cancers should prompt early evaluation of gynecologic or upper aerodigestive tract symptoms for patients with known HPV-related cancers.

Predictors of lymphatic failure in endometrial cancer.

OBJECTIVE: The aim of this study was to identify determinants of lymphatic failure in patients with endometrial cancer after definitive primary treatment. METHODS: We observed 142 relapses in endometrial cancer patients who had primary surgery at our institution during the decade before 1994. We defined lymphatic failure as a relapse occurring on the pelvic sidewall (PSW), para-aortic area (PAA), or other node-bearing area (i.e., groin, axilla, supraclavicular, mediastinal). Mean follow-up was 72.8 months. RESULTS: We observed 44 instances of lymphatic failure--6 on the PSW only, 16 in the PAA only, 12 concomitantly in the PAA and on the PSW, and 10 confined in other node-bearing areas. By univariate analysis, body mass index > or = 30 kg/m(2), para-aortic lymph node biopsy, cervical stromal invasion (CSI), positive adnexa, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, positive lymph nodes (pelvic and/or para-aortic), radiotherapy, grade 3 tumor, nonendometrioid histology, and lymph--vascular invasion (LVI) significantly (P < or = 0.05) correlated with lymphatic failure. However, on Cox regression analysis, only LVI (P < 0.01, relative risk [RR] = 4.27), nodal involvement (P = 0.02, RR = 3.43), and CSI (P = 0.049, RR = 2.26) were independent predictors of lymphatic failure. Moreover, lymph node metastases (P = 0.01, RR = 19.82) and CSI (P = 0.050, RR = 3.57) independently predicted failure on the PSW, and only lymph node involvement (P < 0.01, RR = 10.15) predicted relapse in the PAA. CONCLUSION: LVI, positive lymph nodes, and CSI were the strongest predictors of lymphatic failure in endometrial cancer (31% of patients with at least one of the above three variables had a failure at 5 years). Patients with none of the above three factors had an extremely low (<1%) risk of lymphatic failure.