Gestational Trophoblastic Disorders: An Update in 2015.

Gestational trophoblastic diseases (GTD) are a group of pregnancy-related disorders representing rare human tumours. They encompass premalignant disorders including complete (CHM), partial hydatidiform mole (PHM), exaggerated placental site (EPS), and placental-site nodule (PSN) as well as malignant disorders (also known as "gestational trophoblastic neoplasia [GTN]") including invasive mole, choriocarcinoma (CC), placenta-site trophoblastic tumour (PSTT), and epitheloid trophoblastic tumours (ETT) (Fig. 1). Originally, GTD develop from abnormal proliferation of trophoblastic tissue and form botryoid arranged vesicles. Premalignant moles are usually treated by suction curettage while persistent and recurrent moles and malignant forms require systemic therapy with methotrexate or combination chemotherapy consisting of etoposide, actimomycin D, methotrexate, vincristine, and cyclophosphamide (EMA-CO). ß-human chorion gonadotropin (ß-hCG) plays a crucial role in diagnosis and monitoring therapeutic effects. Since the definitive diagnosis cannot be obtained by histology in most cases, persistent or recurrent disease is diagnosed by elevated or persistent serum levels of ß-hCG. While curing rates are described to be as high as 98 %, GTD may initially present, recur, or end up as a metastasising systemic disease. This underlines the importance of a regular and consistent follow-up after treatment.

The Prevention of Positioning Injuries during Gynecologic Operations. Guideline of DGGG (S1-Level, AWMF Registry No. 015/077, February 2015).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.

Macrophage capping protein CapG is a putative oncogene involved in migration and invasiveness in ovarian carcinoma.

The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

Feasibility and first long-term results after laparoscopic rectal segment resection and vaginal specimen retrieval for deep infiltrating endometriosis.

INTRODUCTION: Radical resection of deep infiltrating endometriosis (DIE), including bladder and bowel resection, provides relief from pain in symptomatic patients. The laparoscopic approach to treatment is well established for bowel resection but normally requires additional abdominal incisions for specimen retrieval. Here we describe our technique of laparoscopically assisted rectal resection and transvaginal specimen retrieval (LARRT) and provide follow-up information on pain scores and complications. MATERIALS AND METHODS: Retrospective observational monocentric study on all DIE patients with rectal infiltration treated between 2008 and 2010 with LATRR at our department. Follow-up was obtained for at least 3 years, including baseline 1-year and 3-year pain scores. RESULTS: We identified four patients undergoing LARRT available for follow-up. DIE was confirmed by histology in all cases. There were no intraoperative complications. Two patients had transient postoperative urinary retention, one patient developed recto-vaginal fistula and required transient colostomy. One patient suffered from persistent vaginal dryness. All patients, however, reported persistent pain relief, including at the end of follow-up period. CONCLUSION: LARRT is a feasible variation of laparoscopic bowel resection for DIE with rectal infiltration. In our study it has promising results with respect to pain control. Larger studies will, however, be required to determine the safety of this procedure.

Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) carrying an imbalance in the native ratio of the two PR isoforms A and B (PR-A and PR-B) through the expression of additional A form and examined their uterine phenotype under different hormonal regimens, using various criteria. Uterine epithelial cell proliferation was augmented in PR-A transgenics and was abolished by PR antagonists. In particular, proliferative response to progesterone, independent of signaling through estrogen, was enhanced. Upon continuous exposure to estradiol and progesterone, the uteri in PR-A transgenics displayed gross enlargement, endometrial hyperplasia including atypical lesions, endometritis and pelvic inflammatory disease. Imbalanced expression of the two isoforms of PR in a transgenic model reveals multiple derangements in the regulation of uterine physiology, resulting in various pathologies including hyperplasias.

Intrauterine fetal death after multiple umbilical cord torsion-complication of a twin pregnancy following assisted reproduction.

BACKGROUND: Patients requiring assisted reproductive techniques may have a higher rate of congenital malformations. Some rare complications of pregnancy might be related to such abnormalities. Torsions of the umbilical cord resulting in fetal death have previously been described exclusively in pregnancies following spontaneous conception. CASE: The case of 37 year old gravida I, para O woman with a twin pregnancy after intracytoplasmatic sperm injection and intrauterine death of one twin at approximately 30 weeks' gestation is presented. The surviving twin was delivered by cesarean section at 31 weeks after spontaneous onset of labor and recurrent fetal bradycardia. The intraoperative situs showed that the demised twin had suffered from multiple umbilical cord torsions leading to intrauterine hypoperfusion. CONCLUSION: Umbilical torsion leading to fetal death might represent a previously unrecognized complication in women requiring assisted reproductive techniques, but this problem is known to occur in pregnancies achieved by natural methods.

Placenta percreta leading to spontaneous complete uterine rupture in the second trimester. Example of a fatal complication of abnormal placentation following uterine scarring.

A 30-year-old gravida 2 para 1 was admitted to hospital 2 years after cesarean section at 20 weeks' gestation with acute onset of abdominal pain and hypovolaemic shock. Emergency laparotomy revealed a uterine rupture located in the anterior uterine wall caused by a placenta percreta and supracervical hysterectomy was performed. This site of invasion and finally rupture was in projection of the previous lower-segment cesarean section. This report illustrates the dramatic consequences of abnormal placentation after prior uterine surgery, which can already occur early during pregnancy and prior to the onset of labour.

Predictors for long-term survival after interdisciplinary salvage surgery for advanced or recurrent gynecologic cancers.

BACKGROUND AND OBJECTIVES: We wanted to identify factors which allow predicting long-term survival after pelvic exenteration (PE) for locally advanced or recurrent gynecologic malignancies. METHODS: All patients undergoing PE at our institution from 1983 to 2002 were screened. In 203 cases data were obtainable and analyzed with respect to factors predicting outcome considering morbidity, mortality, and survival. Follow-up data and data concerning late complications not documented in our records were obtained by telephone interviews. RESULTS: Mean age was 55 (22-77) years. PE was performed for locally advanced (36%) or recurrent (64%) cervical (n = 133), endometrial (n = 26), vaginal (n = 23), vulvar (n = 10), and ovarian cancer (n = 11, cases with rectum and/or bladder resections). In 13.4% (n = 26) the intent of the procedure was palliation in the remaining cure. Procedures performed were anterior (n = 91), posterior (45), or total (n = 67) PE. 53% of patients underwent preoperative radio-chemotherapy, 11.8% as a neoadjuvant treatment. Mean OR time was 8.1 hr, an average of 5.6 units of packed red blood cells were perioperatively transfused. Microscopically complete resection was achievable in n = 69 patients. Perioperative mortality was 1% (n = 2). Seventy-one percent (n = 144) of patients were available for follow-up. Five-year overall survival in patients treated with a curative intent was 21%, 5-year survival in those patients with complete resection was 32%. Forty-two percent of patients with a complete resection without lymph node involvement, age 30-50, curative intention, and the absence of a pelvic sidewall infiltration survived 5 years or longer. CONCLUSION: In our series a 5-year survival rate of over 40% could be achieved for nodal-negative patients without pelvic sidewall infiltration when treated with curative intent and after complete resection.

[Interdisciplinary aspects of surgery of the pelvis minor and retroperitoneum]. / Operative Interdisziplinarität-Kleines Becken und Retroperitoneum.

Surgery of diseases of the pelvis minor and retroperitoneum such as inflammatory disease, malignant tumours, or trauma of pelvic organs need the close interdisciplinary collaboration of visceral surgeons, gynaecologists, and urologists. This collaboration begins in planning diagnostic and therapeutic procedures. It has to be clear who performs which operative step and when. Excellent long-term results in malignant disease show that the greater effort is worthwhile. The rate of postoperative morbidity after these multivisceral resections is high also in specialised centers, but mortality is below 5%. Because of the growing number of long-term survivors, preservation of quality of life becomes more and more important.

Influence of uremia on cell viability and cytokine release of human peritoneal mesothelial cells.

INTRODUCTION: There is still no evidence whether human peritoneal mesothelial cells (HPMC) from patients with end-stage renal failure are altered in cell viability or show a different pattern of the release of proinflammatory cytokines. Also the serum of patients with uremia may contain substances stimulating the cytokine release of HPMC. STUDY DESIGN: The IL-1beta-induced IL-6/IL-8 release of HPMC from healthy donors and from patients with end-stage renal disease (ESRD) were measured before the start of chronic peritoneal dialysis (PD) and during PD therapy. Additionally the influence of uremic and non-uremic serum on IL-6 and IL-8 release of normal HPMC was studied. Cell viability was assessed by MTT assay and by the measurement of intracellular ATP (chemoluminescence assay). HPMC were obtained from the following patient groups: (1) non-uremic control patients (n = 7); (2) patients with ESRD undergoing PD catheter implantation for the first time (n = 7), and (3) patients on PD undergoing catheter exchange for noninfectious reasons (n = 6). Pooled human serum from PD patients and normal controls were used for stimulation experiments. HPMC from different donors were grown to confluence (second passage) and then stimulated with IL-1beta (1,000 pg/ml in M199) for 24 h. IL-6 and IL-8 concentrations were measured in the supernatant by ELISA. Additionally uremic and non-uremic sera were incubated with HPMC from normal donors for 24 h with a subsequent 24-hour IL-1beta stimulation. Mesothelial cell protein mass was determined by the Bradford reagent. RESULTS: Non-uremic patients and ESRD patients did not differ with regard to the global cell viability of HPMC according to MTT assay activity or the intracellular ATP concentration. However, HPMC from uremic patients produced more IL-8 on IL-1beta stimulation than the non-uremic controls (group 2, 53.5 +/- 15.7 pg/microg; group 3, 70.5 +/- 27.3 pg/microg vs. group 1, 24.0 +/- 11.8 pg/microg). HPMC from patients on chronic PD additionally released significantly more IL-6 (30.5 +/- 13.8 pg/microg) on IL-1beta stimulation than uremic patients before the onset of PD (6.2 +/- 2.6 pg/microg; p < 0.01). Incubation of normal HPMC with the serum from uremic donors produced an enhanced stimulated IL-8 release compared to the exposition with normal control serum (50.6 +/- 6.1 vs. 20.8 +/- 2.9 pg/microg; p < 0.01). CONCLUSION: HPMC from uremic patients more readily release IL-8 on stimulation with IL-1beta. On chronic PD treatment IL-6 release was further enhanced. Not further classified serum components in uremia also enhance IL-6 and IL-8 release of HPMC.

[Jejunum interposition as replacement of the pars descendens duodeni in extensive tubulovillous adenoma]. / Jejunuminterponat als Ersatz der Pars descendens duodeni bei ausgedehntem tubulovillösen Adenom.

Reconstruction after partial duodenectomy with resection of the ampulla of Vater is often troublesome. We report the case of a 70-year-old patient with endoscopically non-resectable tubulo-villous adenoma of the descending duodenum including the ampulla of Vater in which subsequent biopsies revealed dysplastic areas. A partial resection of the descending duodenum including the ampulla of Vater was performed. Reconstruction was achieved by the interposition of a jejunal limb in which the ampulla could be reinserted to the posterior wall. The postoperative course was uneventful; a carcinoma was not found within the specimen. In cases of widespread adenomas of the ampulla of Vater, duodenum-preserving resection by interposition of a jejunal limb with reinsertion of the ampulla into the posterior wall may be used as an alternative to Roux-Y reconstruction and to Whipple's procedure.

Eosinophilic pneumonia and respiratory failure associated with venlafaxine treatment.

Drugs are well known causes of eosinophilic lung disease. In many patients, symptoms increase slowly, pulmonary infiltrates and eosinophilia progress over weeks, and resolve upon withdrawal of the offending agent. Rarely, the disease presents like acute eosinophilic pneumonia with acute onset of symptoms and rapidly progressing infiltrates which may be associated with respiratory failure. This report describe a case of venlafaxine-induced acute eosinophilic pneumonia causing respiratory insufficiency that rapidly resolved upon institution of corticosteroid treatment. This 5-hydroxytryptamine and noradrenaline reuptake inhibitor was previously not known to cause lung or peripheral blood eosinophilia. Considering the increasing use of this class of medication physicians have to be aware of this life-threatening and fully reversible complication.