Outcomes of minimally invasive versus open abdominal hysterectomy in patients with gestational trophoblastic disease.

OBJECTIVE: The aim of this study is to compare surgical and oncologic outcomes for women undergoing MIH or open abdominal hysterectomy (OAH) for management of gestational trophoblastic disease (GTD). METHODS: Patients who underwent hysterectomy for GTD between January 1, 2009 and December 31, 2018 were identified using an institutional database and tumor registry. Patients were stratified based on indication for and mode of hysterectomy. RESULTS: 39 patients underwent hysterectomy for GTD - 22 MIH and 17 OAH. 26 hysterectomies (66.7%) were performed for primary treatment of GTD, 7 (17.9%) for chemoresistance, 2 (5.1%) for uterine hemorrhage, and 4 (10.3%) for other indications. Mean tumor size (4.2 vs 4.6 cm; p = .81) and operative time (136 vs 163 mins; p = .42) were similar in both groups. MIH was associated with significantly less blood loss (71.5 vs 427.3 ml; p = .03) and shorter hospital stay (1.5 vs 3.9 days, p = .02) than OAH. Postoperative histology comprised 12 complete moles (6 invasive), 8 choriocarcinomas, 9 placental site trophoblastic tumors and 9 epithelioid trophoblastic tumors. Median follow-up was 67.2 months (50.2 MIH, 79.3 OAH; range 11.1-131.2) and there was no difference in remission (81.8% MIH vs 76.5% OAH; p = .68). There were 7 recurrences (4 MIH, 3 OAH) and 3 deaths (2 MIH, 1 OAH). Overall survival was 97.3% at 2 years and 88.5% at 5 years. There was no significant difference in 5-year survival by mode of surgery (MIH 90.9%, OAH 83.3%; p = .40). CONCLUSIONS: Patients undergoing MIH at our centers have similar oncologic outcomes, lower surgical blood loss and shorter hospital stay compared to those undergoing OAH. Overall survival is similar regardless of mode of surgery.

Multivariable analysis of association of beta-blocker use and survival in advanced ovarian cancer.

OBJECTIVE: In this study, we sought to evaluate the relationship between survival and beta blocker use in both the primary and interval debulking setting while adjusting for frequently co-administered medications. METHODS: We performed a retrospective cohort study reviewing charts of women who underwent primary or interval cytoreduction for stage IIIC and IV epithelial ovarian cancer. The exposure of interest was beta-blocker use identified at the time of cytoreduction. The outcomes of interest were PFS and OS. We collected demographic/prognostic variables and information about use of aspirin, metformin, and statins. We used the Kaplan-Meier method and Cox proportional hazards models in survival analyses. RESULTS: 534 women who underwent surgery for stage IIIC or IV ovarian cancer were included in the study. The median age at diagnosis was 64 and 84.8% of women had serous carcinoma. We identified 105 women (19.7%) on a beta-blocker of whom 94 (90%) were on a cardioselective beta-blocker. Additionally, 24 women (4.5%) were on metformin, 91 (17%) on aspirin, and 128 (24%) on a statin. In univariable analysis, beta-blocker users had a median overall survival of 29 months vs 35 months among non-users (hazard ratio HR = 1.52, p = 0.007). After adjustment for important demographic, clinical, and histopathologic factors, as well as use of other common medications, beta-blocker use remain associated with an increased hazard of death (adjusted HR 1.57, p = 0.006). CONCLUSION: In this retrospective study, we found that patients identified as being on a beta-blocker at the time of surgery had worse overall survival and greater risk of death when compared to those patients not on betablockers. Importantly, 90% of patients on beta-blockers were identified as being on a cardioselective beta-blocker.

Clinicopathologic characteristics associated with long-term survival in advanced epithelial ovarian cancer: an NRG Oncology/Gynecologic Oncology Group ancillary data study.

OBJECTIVE: To identify clinicopathologic factors associated with 10-year overall survival in epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC), and to develop a predictive model identifying long-term survivors. METHODS: Demographic, surgical, and clinicopathologic data were abstracted from GOG 182 records. The association between clinical variables and long-term survival (LTS) (>10years) was assessed using multivariable regression analysis. Bootstrap methods were used to develop predictive models from known prognostic clinical factors and predictive accuracy was quantified using optimism-adjusted area under the receiver operating characteristic curve (AUC). RESULTS: The analysis dataset included 3010 evaluable patients, of whom 195 survived greater than ten years. These patients were more likely to have better performance status, endometrioid histology, stage III (rather than stage IV) disease, absence of ascites, less extensive preoperative disease distribution, microscopic disease residual following cyoreduction (R0), and decreased complexity of surgery (p<0.01). Multivariable regression analysis revealed that lower CA-125 levels, absence of ascites, stage, and R0 were significant independent predictors of LTS. A predictive model created using these variables had an AUC=0.729, which outperformed any of the individual predictors. CONCLUSIONS: The absence of ascites, a low CA-125, stage, and R0 at the time of cytoreduction are factors associated with LTS when controlling for other confounders. An extensively annotated clinicopathologic prediction model for LTS fell short of clinical utility suggesting that prognostic molecular profiles are needed to better predict which patients are likely to be long-term survivors.

Patient, treatment and discharge factors associated with hospital readmission within 30days after surgery for vulvar cancer.

OBJECTIVES: The majority of hospital readmissions are unexpected and considered adverse events. The goal of this study was to examine the factors associated with unplanned readmission after surgery for vulvar cancer. METHODS: Patient demographic, treatment, and discharge factors were collected on 363 patients with squamous cell carcinoma in situ or invasive cancer who underwent vulvectomy at our institution between January 2001 and June 2014. Clinical variables were correlated using χ2 test and Student's t-test as appropriate for univariate analysis. Multivariate analysis was then performed. RESULTS: Of 363 eligible patients, 35.6% had in situ disease and 64.5% had invasive disease. Radical vulvectomy was performed in 39.1% and 23.4% underwent lymph node assessment. Seventeen patients (4.7%) were readmitted within 30days, with length of stay ranging 2 to 37days and 35% of these patients required a re-operation. On univariate analyses comorbidities, radical vulvectomy, nodal assessment, initial length of stay, and discharge to a post acute care facility (PACF) were associated with hospital readmission. On multivariate analysis, only discharge to a PACF was significantly associated with readmission (OR 6.30, CI 1.12-35.53, P=0.04). Of those who were readmitted within 30days, 29.4% had been at a PACF whereas only 6.6% of the no readmission group had been discharged to PACF (P=0.003). CONCLUSIONS: Readmission affected 4.7% of our population, and was associated with lengthy hospitalization and reoperation. After controlling for patient comorbidities and surgical radicality, multivariate analysis suggested that discharge to a PACF was significantly associated with risk of readmission.

Epithelioid trophoblastic tumor: A single institution case series at the New England Trophoblastic Disease Center.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare form of gestational trophoblastic neoplasm which is distinct based on its development from intermediate trophoblast cells and nodular growth pattern. The aim of this study is to describe a case series from a single institution with a review of the literature to better understand the clinical characteristics and outcomes for patients with ETT. METHODS: A retrospective review was performed using the IRB approved New England Trophoblastic Disease Center (NETDC) database from 1998 to 2014. Eight patients were identified of which seven had complete records. Follow-up data was obtained from the longitudinal medical records. RESULTS: Four (57.1%) patients presented with vaginal bleeding and two (28.6%) patients were asymptomatic at presentation. Three (42.9%) patients had extrauterine disease. All three patients with extrauterine disease who received chemotherapy had stable or progressive disease at follow-up. Only two (29%) patients who presented with non-metastatic disease and underwent hysterectomy were alive with no evidence of disease. The mean interval following antecedent pregnancy was 104months. All patients with an interval >4years demonstrated stable or progressive disease despite intensive chemotherapy. Two patients with non-metastatic disease who declined hysterectomy developed stable or progressive disease despite chemotherapy. CONCLUSIONS: This series highlights several features of ETT including the potential for asymptomatic presentation of extrauterine disease. The series also demonstrates chemoresistance, even with multi-agent therapy and a poor prognosis with extrauterine disease and an interval greater than 4years following the antecedent pregnancy suggesting that surgery remains critical in disease control.

Restorative proctocolectomy impairs fertility and pregnancy outcomes in women with ulcerative colitis.

AIM: The effect of restorative proctocolectomy (RPC) on fertility and pregnancy in women with ulcerative colitis (UC) was evaluated. METHOD: Post-RPC female patients with UC who were attempting to become pregnant filled out questionnaires on fertility and pregnancy. Demographic and pouch data of pregnancies ending with delivery were collected from a prospective database. RESULTS: Forty-one women, 44 ± 10 years of age, completed the questionnaires. The median follow-up period post-RPC was 167 (range, 20-352) months. Before RPC, 26 women had 70 pregnancies and 62 deliveries. After RPC, 17 women had 32 pregnancies and 26 deliveries (P = 0.0035). Post-RPC, 10 (37%) of 27 patients failed to conceive compared with 26/26 successful attempts before RPC (P = 0.0006). The number of offspring per patient was 2.38 ± 1.27 before, and 0.68 ± 0.93 after, RPC (P < 0.0001). A higher number of spontaneous pregnancies occurred before (56/62; 90%) than after (15/25; 60%) RPC (P = 0.0004). The time to conception was longer (5.0 ± 11.6 vs 16.3 ± 25.1 months; P = 0.039) and there were more in-vitro fertilization procedures (three vs six) post-RPC. The gestation period was similar, but after RPC more deliveries were by Caesarean section (12.9% vs 46.2%; P = 0.0007). Babies born before RPC weighed more than those born after RPC (3.16 ± 0.61 kg vs 2.79 ± 0.68 kg, respectively; P = 0.0327). CONCLUSION: RPC is associated with an increased risk of infertility, similar duration of gestation and lower birthweight. Female candidates for RPC who have not finished family planning should be counselled accordingly.

Phase II trial of erlotinib in women with squamous cell carcinoma of the vulva.

OBJECTIVE: To evaluate the efficacy and toxicity of erlotinib in the management of squamous cell carcinoma (SCC) of the vulva. METHODS: Patients with vulvar lesions amenable to surgery or chemoradiation (cohort 1) or those with metastatic measurable disease (cohort 2) received erlotinib 150 mg daily. Patients were monitored for toxicity. Responses were determined by digital photography or RECIST 1.1. Cohort 1 underwent pre and post treatment biopsies. EGFR immunohistochemistry (IHC), fluorescence in-situ hybridization (FISH), and mutational analysis were performed. RESULTS: 41 patients were enrolled: 17 in cohort 1 and 24 in cohort 2. Notable grade 3 or 4 toxicities included allergic reaction (1), diarrhea/electrolyte abnormalities (3), ischemic colitis (1), and renal failure (3) and electrolyte abnormalities (n=2). Mean number of cycles for cohort 2 was 3.3. Overall clinical benefit rate was 67.5% with 11 (27.5%) partial responses (PR), 16 (40.0%) stable disease (SD), and 7 (17.5%) progressive disease. Responses were of short duration. All pre and post treatment biopsies exhibited 2-3+ EGFR staining. 5 of 14 patients (35%) were found to have EGFR amplification (n=3) or high polysomy/trisomy (n=2). These five patients had either a PR (n=3) or SD (n=2). Gain of function mutations were not been identified. CONCLUSIONS: This is the first reported controlled trial evaluating erlotinib for the management of vulvar carcinoma. Toxicities were acceptable given the lack of treatment options for these patients. Given the observed clinical benefits erlotinib may represent one of the most active agents available to treat vulvar SCC.

Impact of bowel obstruction at the time of initial presentation in women with ovarian cancer.

OBJECTIVE: To determine whether the presence of bowel obstruction at the time of initial presentation has any prognostic significance in these women. DESIGN: Retrospective cohort study. SETTING: Dedicated gynaecological oncology service of a large tertiary institution. POPULATION: Women who had a bowel obstruction as part of their initial presentation of ovarian cancer were identified between 1995 and 2007. Each woman was matched with four control women (with disease but no obstruction). METHODS: Women with disease were compared with controls to determine the impact, if any, of bowel obstruction at presentation. Several prognostic variables including bowel obstruction were also evaluated in a Cox proportional hazard model. MAIN OUTCOME MEASURES: Progression-free survival (PFS) and overall survival (OS). RESULTS: Forty-eight women with disease and 192 controls were identified during the study period. The median follow-up period was 19 months among women with disease versus 20 months in controls. No differences were seen in demographics and clinical characteristics of the women. Optimal cytoreduction rate was similar between the two groups (75% versus 78%, P = 0.7). Patients with bowel obstruction had a shorter PFS and OS compared with controls [19 months versus 21 months (P = 0.01) and 22 versus 35 months (P = 0.008)], respectively. Bowel obstruction at presentation was an independent prognostic variable with a hazard ratio of 1.5 (P = 0.009). Other prognostic variables were age, stage and extent of surgical cytoreduction. CONCLUSIONS: Bowel obstruction at the time of initial presentation is an adverse prognostic factor in women with ovarian cancer.

A comparison of outcome in patients with stage 1 clear cell and grade 3 endometrioid adenocarcinoma of the endometrium with and without adjuvant therapy.

OBJECTIVE: To determine the outcomes in patients with Stage I uterine clear cell carcinoma (UCCC) treated with and without adjuvant therapy, and to compare the outcomes in these patients to that of matched controls, patients with Stage I, grade 3, endometrioid adenocarcinoma of the endometrium (EC). METHODS: Patients with FIGO Stage I UCCC who underwent comprehensive surgical staging between January 1996 and January 2007 were identified. Cases (UCCC) were matched by age, stage, adjuvant therapy, and year of diagnosis to controls consisting of patients with grade 3 EC. Recurrence and survival were analyzed using the Kaplan-Meier method. RESULTS: 25 patients with Stage I UCCC were identified of whom 13 (52%) received no adjuvant therapy and 12 (48%) received adjuvant radiation therapy (XRT). The 5-year disease-free survival and overall survival rates for the observation and the XRT groups were 78% and 75%, (p = 0.7) and 85% and 82% (p = 0.1), respectively. When compared to controls, the 5-year disease-free survival rates and overall survival rates of patients with Stage I UCCC were not significantly different, 77% vs 75% (p = 0.8) and 84% vs 88% (p = 0.5), respectively. CONCLUSIONS: In patients with Stage I UCCC tumors there was no clear benefit to adjuvant radiation given the absence of improvement in recurrence risk or any survival benefit. These data question the benefit of radiation therapy in UCCC patients with disease confined to the uterus.

Planetary contamination I: the problem and the agreements.

On the contents page of the 24 March issue, the title of the first article should read "Planetary Contamination I: The Problem and the Agreements: N. H. Horowitz, R. P. Sharp, R. W. Davies."

Planetary contamination I: the problem and the agreements.

The sterility requirements for landed spacecraft tentatively adopted in the COSPAR resolution of 1964 are so severe as to pose a major obstacle to planetary exploration. This by itself would not justify modification of the re quirements, since preservation of the biological integrity of Mars is essential for proper exploration of the planet. However, when the physical and biological assumptions underlying the COSPAR recommendations are com pared with actual conditions on Mars, as established by recent observations, it becomes apparent that the COSPAR as sumptions are unrealistic in important respects. Specifically, the belief that eolian erosion on Mars can effect the release of spores trapped in the interior of solids in periods of time that are short compared with the time scale of the unmanned space program is unsup ported by either observation or theory. On the contrary, the analysis suggests that rates of eolian erosion on Mars are very low. Similarly, present knowledge of the Martian environment opposes the view that terrestrial microorganisms would readily contaminate the planet. The combination of dryness, lack of oxygen, and high ultraviolet flux makes the surface of Mars peculiarly unsuit able for the multiplication of terrestrial organisms. Recent studies give little sup port to the proposal that significant areas of geothermal activity exist on Mars. These various findings suggest that the COSPAR-recommended constraints could be substantially relaxed without compromising to any significant degree the biological condition of Mars. In particular, a distinction needs to be made between microorganisms trapped in solids and those on exposed sur faces of landed spacecraft. Surface sterility is an unconditional require ment, in the sense that it is imposed by considerations unrelated to the nature of the Martian environment. Sterilization of the interior of solids to the extreme level recommended by COSPAR, however, is based on the as sumption that entrapped organisms con stitute a substantial hazard to the ecology of Mars. This assumption now seems unjustified, and the need for a high degree of interior sterility is doubt ful. Current spacecraft-sterilization pol icies should be revised accordingly.

The viking carbon assimilation experiments: interim report.

A synthesis of organic matter from atmospheric carbon monoxide or carbon dioxide, or both, appears to take place in the surface material of Mars at a low rate. The synthesis appears to be thermolabile and to be inhibited by moisture.

Injuries from the wichita falls tornado: implications for prevention.

We examined the circumstances of death and injury among victims of the tornado that struck Wichita Falls, Texas, on 10 April 1979. We also assessed the protective measures taken by a representative sample of community residents who suffered no major injury in order to estimate the relative risk of injury to people directly in the tornado's path. Twenty-six (60 percent) of the 43 traumatic deaths and 30 (51 percent) of the 59 serious injuries occurred in people who, despite ample warning, went to their cars to drive out of the storm's path. These people had a risk of serious or fatal injury of 23 per 1000. People who remained indoors and in stationary homes were at relatively low risk (3 per 1000) if they took simple precautions; people in mobile homes were at greatest risk (85 per 1000). Current safety recommendations and housing codes for single family homes and mobile homes need to be amended to decrease the impact of future tornadoes on human health.

Sterile soil from Antarctica: organic analysis.

Soils from the dry-valley region of Antarctica can be sterile by the usual microbiological criteria and yet contain significant amounts of organic carbon. Examination of one such soil shows that the organic material is finely divided anthracite coal. These findings have significant implications for the biological exploration of Mars.

The viking biological investigation: preliminary results.

Three different types of biological experiments on samples of martian surface material ("soil") were conducted inside the Viking lander. In the carbon assimilation or pyrolytic release experiment, (14)CO(2) and (14)CO were exposed to soil in the presence of light. A small amount of gas was found to be converted into organic material. Heat treatment of a duplicate sample prevented such conversion. In the gas exchange experiment, soil was first humidified (exposed to water vapor) for 6 sols and then wet with a complex aqueous solution of metabolites. The gas above the soil was monitored by gas chromatography. A substantial amount of O(2) was detected in the first chromatogram taken 2.8 hours after humidification. Subsequent analyses revealed that significant increases in CO(2) and only small changes in N(2) had also occurred. In the labeled release experiment, soil was moistened with a solution containing several (14)C-labeled organic compounds. A substantial evolution of radioactive gas was registered but did not occur with a duplicate heat-treated sample. Alternative chemical and biological interpretations are possible for these preliminary data. The experiments are still in process, and these results so far do not allow a decision regarding the existence of life on the plonet Mars.

The epidemiology of ovarian granulosa cell tumors: a case-control study.

OBJECTIVE: This study identified risk factors for ovarian granulosa cell tumors (GCT) through a case-control study comparing women with GCT to women with epithelial ovarian cancers (OC) and general population (GP) controls. METHODS: Women with GCT and OC were identified from our hospital tumor board and the Massachusetts and New Hampshire Statewide Cancer Registries between January, 1988 and November, 2008. Age, gender and county matched GP controls were identified through town books in Massachusetts and drivers' license lists in New Hampshire. Epidemiologic factors including age, race, obesity, pregnancy history, smoking, and family history were evaluated. Odds ratio (OR) was calculated and adjusted for race and age. RESULTS: Seventy-two women with GCT, 1578 GP controls, and 1511 OC controls were identified. Patients with GCT were significantly more likely to be non-white (OR 8.49; 4.07, 17.7), obese with a BMI >30 (OR 5.80; 3.01, 11.2), and have a family history of breast (OR 2.13; 1.19, 3.80) or ovarian cancer (OR 2.89; 1.08, 7.72) than GP controls. The risk of developing GCT was significantly decreased in women who smoked (OR 0.46; 0.27, 0.78), used oral contraceptive pills (OR 0.32; 0.17, 0.63) or were parous with 1-2 (OR 0.30; 0.16-0.56) or greater than 2 births (OR 0.50; 0.27, 0.94) when compared to GP controls. CONCLUSION: These findings suggest an independent association between non-white race and obesity as a hyperestrogenic state in the development of GCT while parity and OCP use may be protective. An unknown familial predisposition for GCT may exist.

Clinical trial: evaluation of a clinical decision-support model for upper abdominal complaints in primary-care practice.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) and dyspepsia affect 25-40% of the general population. In the absence of alarm symptoms, the current recommended policy in young dyspeptic patients is a 'test and treat' strategy for Helicobacter pylori; in GERD patients, a therapeutic trial with proton pump inhibitors is the treatment of choice. AIM: To create a short and simple clinical algorithm, for the diagnosis and treatment of patients with upper gastrointestinal complaints. METHODS: The clinical usefulness and cost-effectiveness of the new algorithm were evaluated in a controlled clinical trial, held in primary-care clinics in Israel. Clinical and economical treatment outcomes were evaluated after 1, 3 and 6 months comparing doctors who used the algorithm (cases) vs. those who did not (controls). RESULTS: 78 cases and 54 controls completed the 6 months of follow up. The improvement in symptom severity and quality of life was greater in the cases than in the controls (P < 0.05). General practitioner clinics visits (P = 0.04), gastroenterology clinics visits (P = 0.02) and medication costs (P = 0.004) were all significantly reduced among cases. Controls underwent also more imaging tests (computerized tomography, ultrasound and X-ray) and endoscopies. The average cost for 6 months' treatment and follow-up was $US 199 for cases compared with an average of $US 336 in the control group. CONCLUSION: The use of a clinical decision-support tool can facilitate and promote the implementation of management guidelines by general practitioners. The short algorithm presented in the study was found to be useful and easy to apply in clinical practice. Its effectiveness can be further increased by implementing it in computerized medical systems.

Cellular and extracellular siderophores of Aspergillus nidulans and Penicillium chrysogenum.

Aspergillus nidulans and Penicillium chrysogenum produce specific cellular siderophores in addition to the well-known siderophores of the culture medium. Since this was found previously in Neurospora crassa, it is probably generally true for filamentous ascomycetes. The cellular siderophore of A. nidulans is ferricrocin; that of P. chrysogenum is ferrichrome. A. nidulans also contains triacetylfusigen, a siderophore without apparent biological activity. Conidia of both species lose siderophores at high salt concentrations and become siderophore dependent. This has also been found in N. crassa, where lowering of the water activity has been shown to be the causal factor. We used an assay procedure based on this dependency to reexamine the extracellular siderophores of these species. During rapid mycelial growth, both A. nidulans and P. chrysogenum produced two highly active, unidentified siderophores which were later replaced by a less active or inactive product--coprogen in the case of P. chrysogenum and triacetylfusigen in the case of A. nidulans. N. crassa secreted coprogen only. Fungal siderophore metabolism is varied and complex.