[Metastatic mechanisms of uterine malignancies and therapeutic consequences]. / Metastasierung von Malignomen des Uterus und therapeutische Konsequenzen.

Malignancies of the uterus metastasize by direct invasion of neighboring structures, lymphatically or hematogenously. Endometrial and cervical cancers lymphatically spread to the pelvic and para-aortic lymph nodes. For endometrial cancer the depth of myometrial invasion, lymphosvascular space involvement (LVSI) and a microcystic, elongated and fragmented (MELF) glandular invasion pattern are predictors for lymph node metastases. Metastases to the pelvic lymph nodes occur in approximately 10 % of endometrial cancer patients and in 30 % of these cases the para-aortic lymph nodes are also involved. Sentinel lymph node biopsy is possible for clinical stage I endometrial cancer and early stages of cervical cancer but is not yet routine. The presence of LVSI is considered to be the strongest predictor of distant metastases, particularly if assessed by immunohistochemistry with antibodies against factor VIII-related antigen or CD31. Endometrioid and clear cell carcinomas can hematogenously metastasize to the lungs, bones, liver and brain and can rarely be manifested as a solitary metastasis. In contrast, serous carcinomas can show extensive peritoneal spread. To date molecular biomarkers cannot predict the occurrence of distant metastasis. Overexpression of P53, p16 and L1CAM have been identified as negative prognostic factors and are associated with the prognostically unfavorable serous tumor type. The metastatic spread of squamous cell cervical cancer is strongly associated with tumor volume. Microinvasive carcinomas have a very low rate of parametrial and lymph node involvement and do not require radical hysterectomy. In contrast, lymph node metastases occur in up to 50 % of bulky stages IB and II cervical cancers. Distant metastases can occur in the lungs, liver, bones and brain. Molecular biomarkers have not been shown to predict metastatic spread. In well-differentiated adenocarcinoma of the cervix the pattern of invasion is strongly predictive for the presence of lymph node metastases, irrespective of tumor size and depth of invasion.

Recurrence in a Schuchardt incision after Schauta-Amreich radical vaginal hysterectomy for cervical cancer.

A Schuchardt incision is frequently performed to facilitate access to the parametrium during radical vaginal hysterectomy for cervical cancer. We report an adenocarcinoma recurrence in a Schuchardt incision 12 months after radical vaginal hysterectomy for FIGO stage IB1 cervical cancer. Histology of the primary tumor had shown a well-differentiated adenocarcinoma and poorly differentiated squamous cell carcinoma of the cervix 2.6 cm in maximum diameter. After further surgical therapy and adjuvant radiotherapy, the patient died of disease 51 months after the initial operation. Cervical cancers can implant and recur in perineal incisions. Thus, it appears prudent to avoid such incisions or, if they are made, to irrigate them copiously before closing them.

Tension-free vaginal tape operation: results of the Austrian registry.

OBJECTIVE: To assess the use of and perioperative complications associated with the tension-free vaginal tape operation with a central registry. METHODS: Fifty-five gynecology units completed questionnaires on patients undergoing the tension-free vaginal tape operation. Information was collected on patient, surgical, and postoperative data. RESULTS: A total of 2795 patients were entered. Overall, 773 patients (28%) had undergone previous surgery for incontinence or prolapse; 1640 (59%) tension-free vaginal tapes were performed as isolated operations, and 1155 (41%) were done in combination with other procedures. The median operating time for tension-free vaginal tapes alone was 30 minutes (range 10-120). Of the isolated tension-free vaginal tapes, 727 (44%) were performed with local, 711 (43%) with regional, and 193 (12%) with general anesthesia. In patients undergoing tension-free vaginal tape only, postoperative bladder drainage was obtained with intermittent catheterization in 389 (24%) patients, an indwelling urethral catheter in 1032 (63%), and a suprapubic catheter in 143 (9%). The bladder perforation rate was 2.7% overall (n = 75) and higher in patients with than in those without previous surgery (4.4% compared with 2.0%, P =.01). There were four bladder perforations (3.3%) among the 120 patients with previous colposuspension. Most patients undergoing tension-free vaginal tape only were able to void the next day (range 0 to over 64). A total of 68 patients (2.4%) required reoperation for reasons related to the tape (39 to loosen, remove, or cut the tape, or to place a suprapubic catheter, 19 for hematoma, one for bowel injury). CONCLUSION: The tension-free vaginal tape has become a frequently performed operation in Austria. There are considerable variations in clinical practice. The risk of bladder perforation was increased in patients with previous surgery. Severe complications were rare.

Pretreatment hemoglobin, platelet count, and prognosis in endometrial carcinoma.

We analyzed whether a low pretreatment hemoglobin level is a prognostic factor in endometrial cancer and whether it is associated with thrombocytosis. Two hundred and twelve patients with endometrial cancer treated with surgery were reviewed. Data were analyzed with Pearson's chi-squared test, Fisher's exact test in contingency tables, the Mann-Whitney U-test, the Student's t-test, and Kaplan-Meier estimates. Multivariate analysis was performed with the log-rank test and the Cox proportional hazard model. Thirty-nine patients (18%) had a pretreatment hemoglobin value of < 12.0 g/dL. These 39 patients had significantly higher rates of nonendometrioid histology, high-grade tumors, myometrial invasion of > 50%, adnexal involvement, lymph-vascular space involvement, and advanced FIGO stage than patients with hemoglobin > or = 12.0 g/dL. The rate of thrombocytosis was significantly higher in patients with a low hemoglobin level (36% vs. 8%, P < 0.01). The overall 5-year survival rate of patients with low pretreatment hemoglobin was 59% compared with 89% for those with hemoglobin > or = 12 g/dL (P < 0.01). In the multivariate analysis age, thrombocytosis, nonendometrioid histology, high-grade histology, and advanced FIGO stage were significantly associated with a poor prognosis whereas adnexal involvement, lymph-vascular space involvement, low hemoglobin and myometrial invasion were not. These data indicate that low pretreatment hemoglobin is a prognostic factor in patients with endometrial cancer and that it is associated with thrombocytosis. Low hemoglobin was strongly associated with other unfavorable prognostic factors so that it was significant in the univariate but not the multivariate analysis.

Effect of fetal hyperinsulinism on oral glucose tolerance test results in patients with gestational diabetes mellitus.

OBJECTIVE: This study was undertaken to evaluate the impact of the fetoplacental glucose steal phenomenon on the results of oral glucose tolerance testing in pregnancies complicated by gestational diabetes mellitus with fetal hyperinsulinism. STUDY DESIGN: This was an analysis of the cases of 34 patients with two consecutive abnormal oral glucose tolerance test results and amniotic fluid insulin measurement before institution of insulin therapy. Patients were divided into groups on the basis of normal versus elevated amniotic fluid insulin concentrations. RESULTS: Oral glucose tolerance tests were done at a mean (+/-SD) of 24.9 +/- 5.7 and 30.7 +/- 3.2 weeks' gestation, and amniotic fluid insulin measurements were done at 31.1 +/- 3.2 weeks' gestation. In 13 women with gestational diabetes mellitus with normal amniotic fluid insulin concentration, maternal postload blood glucose levels at 1 hour increased by 12 mg/dL (168 vs 180 mg/dL; 9.3 vs 10.0 mmol/L; P = .0006) during the course of 6 weeks. In contrast, in 21 women with gestational diabetes mellitus with elevated amniotic fluid insulin levels (>7 microU/mL; >42 pmol/L), 1-hour postload blood glucose levels decreased by 22 mg/dL (201 vs 179 mg/dL; 11.2 vs 9.9 mmol/L; P = .002) during the same period. The higher the amniotic fluid insulin level, the larger the decrease (R = 0.504; P =.02). Although low amniotic fluid insulin levels were correlated significantly with 1-hour glucose levels of the first and second oral glucose tolerance tests, high insulin levels were no longer correlated with the second oral glucose tolerance test. CONCLUSION: Exaggerated fetal glucose siphoning may provide misleading oral glucose tolerance test results in pregnancies complicated by fetal hyperinsulinism by blunting maternal postload glucose peaks. Consequently, oral glucose tolerance test results in a pregnancy complicated by gestational diabetes mellitus with a fetus that already has hyperinsulinemia may erroneously be considered normal.

Gastrointestinal surgery in patients with ovarian cancer.

OBJECTIVES: The objectives were to assess indications for and outcome and morbidity of gastrointestinal surgery in patients with ovarian cancer. METHODS: We reviewed 364 patients with ovarian cancer who underwent a total of 491 operations including a gastrointestinal procedure over a 10-year period. The 491 operations comprised 180 primary surgical procedures (37%), 44 second-look laparotomies (9%), and 267 procedures for recurrence or palliation (54%). RESULTS: Debulking of disease was the indication for bowel surgery for 87, 45, and 62% of cases in the three groups, respectively. Bowel obstruction was an indication in 14% of patients at primary surgery and in 34% at secondary surgery (P < 0.05). Rectosigmoid resection was the most common bowel operation overall, particularly in the primary surgery group (65%). Colostomy was performed in 30% of the cases of rectosigmoid resection at primary surgery. Small-bowel resection was most common in the surgery for recurrence or palliation group. The blood transfusion rate was 79%. Febrile morbidity was the most common complication overall (29%), with no significant differences among groups. Four patients (0.8%) required reoperation for an abscess or anastomotic leak. Nineteen operations (3.9%) were followed by death within 30 days, with no significant differences among groups. A weighted Cox model estimated that 21, 42, and 11% of patients would be alive 5 years after primary surgery, second-look laparotomy, and surgery for recurrence or palliation, respectively (P = 0.01). CONCLUSION: Gastrointestinal surgery is frequently indicated during operations for ovarian cancer. Gynecologic cancer surgeons should be trained accordingly. Patients with possibly malignant ovarian masses should receive preoperative bowel preparation and be counseled that bowel surgery may be needed but colostomy is not frequently required.

Long-term follow-up of infants of mothers with type 1 diabetes: evidence for hereditary and nonhereditary transmission of diabetes and precursors.

OBJECTIVE: To estimate the impact of type 1 diabetes during pregnancy on transgenerational genetically caused and/or fuel-mediated amplification of types 1 and 2 diabetes and to estimate the impact of elevated amniotic fluid insulin levels. RESEARCH DESIGN AND METHODS: A total of 75 white offspring of type 1 diabetic mothers and 49 control subjects of similar age and pubertal stage were examined at 5-15 years of age. All offspring had an oral glucose tolerance test. Glucose, insulin, and C-peptide were measured at 0, 30, 60, and 120 min after loading. Lipids and autoimmune antibodies were measured in fasting plasma. RESULTS: Of the 75 offspring, 4 (5.3%) had overt diabetes, and 16 of 71 (22.5%) had autoimmune antibodies. Offspring of diabetic mothers had significantly higher BMI; symmetry indexes; cholesterol, glucose, insulin, and C-peptide levels; and insulin resistance than control subjects. With the exception of cholesterol, these values were significantly elevated in offspring who had elevated amniotic fluid insulin levels (>8 microU/ml, >48 pmol/l) during pregnancy compared with normoinsulinemic offspring and control subjects. CONCLUSIONS: Offspring of type 1 diabetic mothers have an increased risk for diabetes later in life. The relative risk for type 1 and type 2 diabetes is 71.6 and 3.2, respectively. Type 2 diabetes-associated risk factors, such as high BMI; elevated glucose, insulin, and C-peptide levels; and insulin resistance, are related to the fetal metabolic experience in utero, as reflected by amniotic fluid insulin concentration.

Intra-abdominal desmoplastic small round cell tumor in a 68-year-old female.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) of the peritoneum typically occurs in young adults. The mean age of females with DSRCT is 20 years. We describe a DSRCT with an unusual age of presentation mimicking a metastatic ovarian neoplasm. CASE: A 68-year-old para 4 female presented with abdominal enlargement. Laparatomy showed multiple tumor nodules attached to the peritoneal surface. The tumor was debulked. The histological findings were characteristic for DSRCT. Adjuvantly the patient received cytotoxic chemotherapy but died of recurrent disease 3 months after initial diagnosis. CONCLUSION: DSRCT should be added to the differential diagnosis of unusual gynecologic malignancies in elderly as well as younger females. Identification of DSRCT is important because it can be confused with primary ovarian neoplasms.

Parametrial spread in patients with endometrial carcinoma undergoing radical hysterectomy.

The objective of this paper is to study parametrial involvement in patients with endometrial carcinoma undergoing radical hysterectomy. We reviewed indications for surgery, pathology findings, and outcome of a series of 24 patients with endometrial carcinoma who underwent radical hysterectomy. The uterus, cervix and parametrial tissue were processed as step-serial sections. Histologically, 16 patients (67%) had carcinoma involving the cervix. Two of these patients (8%) had frank histologic parametrial involvement and four (17%) had disease extending to the transitional zone of the cervix. Parametrial involvement was continuous and seen only in patients with involvement of the cervical stroma. Six patients (25%) had pelvic node metastases. With a median follow-up of 53 months (range 2-140), four patients (17%) developed recurrences (all within 24 months). Twelve patients (50%), including one of the two with parametrial invasion, were free of disease for 5 years or longer. We conclude that direct parametrial extension can occur in locally advanced endometrial cancer. Radical hysterectomy with lymphadenectomy can be an adequate operation for such patients.

Long-term survival of a patient with fallopian tube cancer presenting with a supraclavicular mass.

BACKGROUND: Five-year survival of patients with stage IV cancer of the fallopian tube is poor. Furthermore, patients with gynecological cancers presenting with a supraclavicular mass generally have an unfavorable prognosis. CASE REPORT: We describe a 70-year-old patient who presented with a left supraclavicular mass. The mass was removed and histology showed metastatic papillary adenocarcinoma strongly suggestive of papillary serous carcinoma. Abdominal hysterectomy and salpingo-oophorectomy showed a primary carcinoma of the fallopian tube. Postoperatively the patient received six cycles of carboplatin-based chemotherapy and is alive and well with no evidence of disease 5 years and 10 months after the primary diagnosis. CONCLUSION: Surgery and adjuvant carboplatin-based chemotherapy seem justified even in older patients with fallopian tube cancer and distant metastasis at the time of diagnosis.

Five-year results after anti-incontinence operations.

OBJECTIVE: This study was undertaken to evaluate continence rates 5 years after anterior colporrhaphy, anterior colporrhaphy with needle suspension of the bladder neck, and Burch colposuspension. STUDY DESIGN: Among 544 women with stress incontinence who were operated on between 1989 and 1993, 327 women (60%) underwent clinical and urodynamic reevaluation 5 years after the operation. Choice of surgical procedure was made on the basis of clinical and urodynamic findings and of physician preference. Continence was defined as no loss of urine during cystometry or during coughing with the bladder filled to 300 mL. RESULTS: The 327 patients underwent a total of 334 operations. The objective overall continence rates at 5 years were 61% (65/107) after anterior repair, 49% (59/121) after anterior repair with needle suspension, and 79% (84/106) after Burch colposuspension. Continence rates after anterior colporrhaphy were 82% (32/39) among patients with mild stress incontinence but 49% (33/68) among those with moderate or severe incontinence (P <.02). Continence rates among patients with moderate or severe incontinence were 49% (59/121) after anterior repair with needle suspension and 79% (84/106) after the Burch operation (P <.02). CONCLUSION: Anterior colporrhaphy can cure mild stress incontinence but is inadequate to correct severe incontinence. Additional needle suspension may be of benefit for patients with moderate to severe incontinence. Abdominal colposuspension is superior to the vaginal operations for long-term cure of stress incontinence.

Inguinal lymph node metastasis as the only manifestation of lymphatic spread in ovarian cancer: A case report.

OBJECTIVE: Inguinal metastasis is a rare manifestation of ovarian cancer. Autopsy studies have reported inguinal metastasis in 0-3% of patients with advanced disease. CASE REPORT: We describe a 43-year-old patient with ovarian cancer limited to the adnexa who had an isolated metastasis in an enlarged inguinal lymph node. The patient underwent total abdominal hysterectomy, omentectomy, pelvic and paraaortic lymphadenectomy, and excision of the enlarged inguinal lymph node. All 78 pelvic and 40 paraaortic lymph nodes were negative. CONCLUSION: This case demonstrates that early isolated distant lymph node metastasis, although rare, can occur in patients with ovarian cancer and may be a presenting symptom.

Ureteral complications with operative gynecologic laparoscopy.

OBJECTIVE: The study assessed the incidence, diagnosis, management, and causes of ureteral injuries during major laparoscopic operations at our department in a 6-year period. STUDY DESIGN: The study was a chart review of 790 consecutive major laparoscopic procedures in 711 patients (mean age 37.4 +/- 11.6 years, mean weight 64.3 +/- 29.1 kg). RESULTS: There were four ureteral complications in three patients during or after laparoscopic operations: three of 711 patients (0.42%) and four of 790 procedures (0.38%). All three ureteral complications (one transection and a total of three ureterovaginal fistulas in two patients) occurred during laparoscopically assisted vaginal hysterectomies, for an incidence of 4.3%. There were no ureteral injuries in 291 salpingo-oophorectomies, 414 ovarian cystectomies, and 15 colposuspensions. Both delayed ureteral complications occurred in the lower segment of the ureter after laparoscopic bipolar coagulation and division of the cardinal ligament. CONCLUSION: We conclude that in laparoscopic surgery the ureter is most at risk when the cardinal ligament is dissected and divided below the uterine vessels.