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Abstract Objective Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. Methods Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. Results A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. Conclusion Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM. Highlights • Unexpected uterine malignancies after hysterectomy were rare with an incidence of 44/10.765 (0.42%). • Most unexpected uterine malignancies were endometrial carcinomas (0.31%), with only few uterine sarcomas (0.11%). • Outcome of patients with unexpected uterine malignancies is favorable, particularly for unexpected endometrial carcinomas. • So far no patient treated with intraoperative power morcellation has had an locoregional relapse. • Thorough preoperative workup and expert pathology are important for optimal patient treatment. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To preclinical assess the feasibility of combining oncolytic measles vaccine virus (MeV) with suicide gene therapy for ovarian cancer treatment. Methods: We genetically engineered a recombinant MeV armed with a yeast-derived bifunctional suicide gene that encodes for cytosine deaminase and uracil phosphoribosyltransferase (MeV-SCD). From this suicide gene, a chimeric protein is produced that converts the non-toxic prodrug 5-fluorocytosine (5-FC) into highly cytotoxic 5-fluorouracil (5-FU) and directly into 5-fluorouridine monophosphate (5-FUMP) thereby bypassing an important mechanism of chemoresistance to 5-FU. Results: MeV-SCD was demonstrated to infect, replicate in and effectively lyse not only human ovarian cancer cell lines, but also primary tumor cells (albeit at lower efficiencies) that were derived from malignant ascites of ovarian cancer patients. Addition of the prodrug 5-FC significantly enhanced cell killing. Importantly, precision-cut tumor slices of human ovarian cancer patient specimens were efficiently infected with MeV-SCD. The prodrug-converting enzyme SCD was expressed by all infected tumor slices, thereby ensuring provision of the suicide gene arming function in patient-derived materials. Conclusions: With respect to safety and therapeutic impact, arming of oncolytic measles vaccine virus warrants further clinical investigation for ovarian cancer treatment. [Copyright &y& Elsevier]

Abstract: Objective: Since 2003, multiple cases of bisphosphonate-induced osteonecrosis of the jaw (ONJ) were reported. The aim of this study was to describe the incidence and risk factors of ONJ in patients with breast cancer or gynecological malignancies receiving bisphosphonates (BP). Methods: ONJ was recorded for all patients with breast cancer or gynecological malignancies treated with intravenous bisphosphonates at the Department of Gynecology and Obstetrics, University Hospital Tuebingen during April, 1999 and May, 2006. Results: 10 of 345 (2.9%) patients with breast cancer or gynecological malignancies developed ONJ while receiving bisphosphonate therapy. Six patients with ONJ had a history of recent dental procedures. All patients had received zoledronic acid as part of their bisphosphonate regimen. Time of exposure to bisphosphonates and the number of treatment cycles were significant risk factors for the development of ONJ (p <0.001). In patients diagnosed with ONJ the mean number of treatment cycles was 27±18 cycles. However, the mean number of treatment cycles in patients without manifestation of ONJ was 12±12 cycles. Conclusion: Length of exposure to BPs and the cumulative dose of given BPs seem to be the most important risk factors for the development of ONJ followed by dental procedures. [Copyright &y& Elsevier]

Abstract: Objectives. : The presence of disseminated tumor cells (DTC) in breast cancer patients is associated with poor prognosis. However, there are limited data about the prevalence and prognostic impact of DTC in patients with gynecological tumors. The aim of this study was to evaluate the presence of DTC in the bone marrow (BM) of patients with gynecological cancers and to correlate their presence with established prognostic factors. Methods. : BM aspirates of 201 patients with primary ovarian (n =69), cervical (n =54) and endometrial cancer (n =78), undergoing surgery at the Department of Gynecology and Obstetrics, University Hospital, Tuebingen, Germany between 1/2002 and 01/2006, were included into the study. Cytokeratin (CK)-positive cells were identified by immunocytochemistry using the pancytokeratin antibody A45B/B3. Results. : The bone marrow positivity rate was 36% in ovarian, 26% in cervical and 17% in endometrial cancer, respectively. Presence of DTC was significantly correlated with FIGO (International Federation of Gynecology and Obstetrics) tumor stage (p <0.05). The recurrence rate was 14% in patients with CK-positive cells compared to 8% in CK-negative patients (p =0.2). There was no correlation between DTC and other established prognostic factors including nodal status or grading except for cervical cancer. Patients with positive lymph node status were more likely to be bone marrow positive compared to those with negative lymph node status (p <0.05). Conclusions. : Disseminated tumor cells seem to be a general phenomenon in epithelial tumors even though their clinical impact remains to be evaluated. The hypothesis that bone marrow is the homing site of disseminated tumor cells is further supported by these data since gynecological tumors only rarely metastasize to the skeletal system. [Copyright &y& Elsevier]

Objectives. We performed a phase I–II study in patients with ovarian and other gynecological cancers to determine the dose-limiting toxicities, maximum tolerated dose (MTD) and efficacy of docetaxel/carboplatin.Methods. Thirty patients were treated in three cohorts with carboplatin (AUC 5) and escalating docetaxel (60, 75 and 90 mg/m2), administered intravenously on day 1, repeated every 3 weeks. Premedication consisted of 16 mg dexamethasone per os on day −1, and +1 and 4 mg intravenously before docetaxel.Results. A total of 6, 11 and 12 patients were eligible and treated on dose levels 1, 2 and 3, respectively. At docetaxel 90 mg/m2, febrile and prolonged neutropenia were dose-limiting, and 75 mg/m2 with carboplatin AUC 5 was considered the MTD. Prolonged neutropenia occurred in two, four and nine patients of dose levels 1–3, respectively, and febrile neutropenia in 2, 1, and 2 patients of dose level 1–3. Thrombocytopenia grade 4 was observed in one patient of dose level 1. Non-hematological toxicity including neuropathy was usually mild across all dose levels. Overall response rate was 73%. Median time to progression was 18.0 months, and median overall survival will exceed 24.4 months.Conclusions. Docetaxel/carboplatin can be safely administered to patients with gynecological cancer despite substantial myelotoxicity and appears to be active in the treatment of ovarian cancer. Low neurotoxicity offers an option for comparison with paclitaxel-containing regimens. [Copyright &y& Elsevier]

Case. A 33-year-old woman presenting with endometrial cancer stage FIGO Ic. After hysterectomy, bilateral oophorectomy and lymph node dissection, combined radiotherapy was indicated. Computer tomography scan was performed to plan radiotherapy and large bowel adhesions were found. To prevent bowel complications during radiation therapy, laparoscopic enterolysis of the adhesions was performed. We were able to start and apply radiation therapy only 22 days after initial laparotomy. Our patient had a history of deep vein thrombosis as a result of oral contraceptive medication. The endoscopic treatment enabled us to shorten the time of immobilization and bed rest substantially.Conclusion. Laparoscopy is an appropriate method to prevent complications due to radiotherapy. [Copyright &y& Elsevier]

Abstract: Background: Primary carcinoma of the Bartholin''s gland is rare, consequently standard management is not clear. Although the sentinel concept has gained popularity for other malignancies of the female reproductive tract, the literature lacks reports of this approach for carcinomas of the Bartholin''s gland. Case: We present a patient with stage I adenocarcinoma of the Bartholin''s gland. She was managed with wide excision and inguinal and laparoscopic pelvic sentinel lymphadenectomy followed by complete pelvic lymphadenectomy. We discuss the rationale for the sentinel concept. Conclusion: As for other gynaecological malignancies the sentinel lymphadenectomy seems to be an appropriate and feasible surgical approach for early stage carcinomas of the Bartholin''s gland. [Copyright &y& Elsevier]