Histopathological study of precursor and neoplastic lesions of endometrium in endometrial samplings

Background: Endometrial lesion presenting as abnormal uterine bleeding, abdominal pain and menstrual irregularities form most common presenting complaint in women of reproductive age group and in premenopausal women. Endometrial sampling is a safe and effective diagnostic step in evaluation of abnormal uterine bleeding (AUB). The present study was carried out to establish histopathological diagnosis of precursor and neoplastic lesions of endometrial samplings in correlation with clinical details and other investigations.Methods: A two-year prospective study was carried out in the department of pathology in a tertiary care hospital from June 2013-May 2015 which included endometrial samplings of precursor and neoplastic lesions. All cases were analyzed histopathologically.Results: The study included 46 cases comprising 30% of total 153 endometrial samplings. Out of these, precursor lesions were 36 cases (23.6%) and malignant were 10 case (5.8%). The highest incidence of precursor lesions (endometrial hyperplasia) was in the age group of 41- 50 years. Among the precursor lesions, endometrial hyperplasia without atypia (86%) was the commonest observation followed by atypical hyperplasia (14%).Conclusions: For the correct evaluation of cases presenting with AUB, histopathological evaluation of endometrial samplings is the gold standard method

Utilization and Outcomes of Patients with Colorectal Cancer Liver Metastases in the Medicare Population

Aggressive treatment of colorectal liver metastases (CRLM) after colectomy is increasing in the last two decades with reports of improved survival. Multiple treatment options are available for CRLM but their use and utility remains unknown. Methods: Using SEER-Medicare linked database (1991-2005), we identified 7131 patients who had undergone colectomy with CRLM. Demographic, clinical and tumor factors were examined as determinants of therapy. Treatment options consisted of surgery (resection, ablation) or chemotherapy. Univariate and multivariate analyses were performed to determine predictors of overall survival after colectomy. Results:635 patients (8.9%) underwent liver directed surgery defined as either a liver resection (n=495), ablation (n=216) or both (n=76) for CRLM. 322 patients (51%) were female and 313 (49%) were male. 147 patients (23%) were SES 1, 230 patients (36%) were SES 2, and 258 (41%) were SES 3. There was a survival advantage to receiving liver surgery or chemotherapy in selected patients with CRLM (p Conclusion: In the Medicare population, patients with CRLM who receive potentially curative therapy such as resection, ablation or chemotherapy experience a substantial survival advantage; despite this only 8.9% of patients received directed therapy for their metastasis. Barriers to treatment and its underutilization must be identified to improve survival in patients diagnosed with CRLM after colectomy

Endemic Gallbladder Cancer: Is There a Role for Prophylactic Cholecystectomy?

Background: Gallbladder cancer (GBC) is an often lethal malignancy with variable distribution. Incidence in the United States is low. However, in areas of Central/South America, Central Europe, Japan, and the Indian subcontinent, GBC is a major cause of cancer death. Cholecystectomy is safe and commonly performed worldwide. Thus, prophylactic cholecystectomy (PCCY) has been proposed in regions with endemic GBC. We developed a simple decision model to assist caregivers in determining the optimal strategy for managing GBC based on local incidence and technological capabilities. Methods: Rates of disease and outcomes were derived from a review of the literature. Using TreeAge-Pro software, a decision model was created to simulate expected health outcomes for populations with high GBC incidence, following 3 treatment strategies: no early intervention, one-time screening ultrasound (US), or PCCY. Lifetime cancer-specific survival was the outcome of interest. Sensitivity analyses were performed to determine threshold values. Results: Based on our model, populations where lifetime risk of GBC exceeds 0.4% may benefit from early intervention by US or PCCY. Two-way sensitivity analysis shows that over a relatively narrow range of disease incidence, US may be favored if sensitivity exceeds 50%. In many cases where lifetime risk exceeds 1%, PCCY may improve survival. Conclusions: GBC varies in incidence, but affects many individuals in some populations in the Americas. The lethality of GBC may justify aggressive public health intervention including screening or prophylactic cholecystectomy. Decision analysis models using best-available evidence may help determine the optimal treatment of individuals at risk for GBC

Rates of Insurance for Injured Patients before and after Health Care Reform in Massachusetts: Another Case of Double Jeopardy?

Background: As a result of healthcare reform (HCR), insurance rates among Massachusetts (MA) residents increased from 86.6% (2006) to 94.4% (2010) and conferred a 7.6% higher probability of being insured compared to neighboring states. The effect of an individual mandate on insurance rates among trauma patients is unknown. Methods: This was retrospective analysis of adult (18-64yrs) trauma patients from MA and surrounding states (NH, RI, CT, NY, VT) treated at our level 1 trauma center in central MA before (2004-2005) and after (2009-2010) MA-HCR. We estimated changes in insurance rates across time-periods and state-residence. Results: Before MA-HCR, 76.7% (1647/2,148) of injured MA residents had insurance compared to 84.3% (2088/2477) post-HCR (p Conclusions: In this single center study, time rather than HCR resulted in modest increases in insurance rates. However, MA-HCR was ineffectual at increasing insurance among trauma patients to levels comparable to the general public, suggesting certain factors may place certain subgroups in “double jeopardy” by simultaneously increasing risk of injury and precluding compliance with an individual mandate

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Inhibition of Ovarian Cancer Cell Spheroid Formation by Synthetic Peptides Derived from Nectin-4

The formation of 3D multicellular spheroids in the ascites fluid of ovarian cancer patients is an understudied component of the disease progression. Spheroids are less sensitive to chemotherapy, in part due to the protection afforded by their structure, but also due to their slower proliferation rate. Previous studies suggest that the cell adhesion molecule Nectin-4 plays a key role in the formation of ovarian cancer spheroids. In this study, we further examined the role of Nectin-4 at early time points in spheroid formation using real-time digital photography. Human NIH:OVCAR5 ovarian cancer cells formed aggregates within 8 h, which further contracted into compact spheroids over 24 h. In contrast, Nectin-4 knockdown cells did not form tightly compacted spheroids. Synthetic peptides derived from Nectin-4 were tested for their ability to alter spheroid formation in two ovarian cancer cell lines. Nectin-4 peptide 10 (N4-P10) had an immediate effect on disrupting ovarian cancer spheroid formation, which continued for over 24 h, while a scrambled version of the peptide had no effect. N4-P10 inhibited spheroid formation in a concentration-dependent manner and was not cytotoxic; suggesting that N4-P10 treatment could maintain the cancer cells as single cells which may be more sensitive to chemotherapy

Is routine intraoperative cholangiogram necessary in the twenty-first century? A national view

INTRODUCTION: Intraoperative cholangiogram (IOC) can define biliary ductal anatomy. Routine IOC has been proposed previously. However, current surgeon IOC utilization practice patterns and outcomes are unclear. METHODS: Nationwide Inpatient Sample 2004-2009 was queried for patients with acute biliary disease undergoing cholecystectomy (CCY). Analyses only included surgeons performing \u3e/=10 CCY/year. We dichotomized surgeons into a routine IOC group vs. selective. Outcomes included bile duct injury, complications, mortality, length of stay, and cost. RESULTS: Of the nonweighted patients, 111,815 underwent CCY. A total of 4,740 actual surgeon yearly volumes were examined. On average, each surgeon performed 23.6 CCYs and 7.9 IOCs annually, using IOC in 33 % of cases. The routine IOC group used IOC for 96 % of cases, whereas selective IOC group used IOC approximately 25 % of the time. Routine IOC surgeons had no difference in mortality (0.4 %) or rate of bile duct injury (0.25 vs. 0.26 %), but higher overall complications (7.3 vs. 6.8 %, p = 0.04). Patients of routine IOC surgeons received more additional procedures and incurred higher costs. CONCLUSION: Routine IOC does not decrease the rate of bile duct injury, but is associated with significant added cost. Surgeons\u27 routine use of IOC is correlated with increased rates of postsurgical procedures, and is associated with increased overall complications. These data suggest routine IOC may not improve outcomes

National trends in pancreaticoduodenal trauma: interventions and outcomes

OBJECTIVES: Pancreaticoduodenal trauma (PDT) is associated with substantial mortality and morbidity. In this study, contemporary trends were analysed using national data. METHODS: The Nationwide Inpatient Sample for 1998-2009 was queried for patients with PDT. Interventions including any operation (Any-Op) and pancreas-specific surgery (PSURG) were identified. Trends in treatment and outcomes were determined [complications, length of stay (LoS), mortality] for the Any-Op, PSURG and non-operative (Non-Op) groups. Analyses included chi-squared tests, Cochran-Armitage trend tests and logistic regression. RESULTS: A total of 27 216 patients (nationally weighted) with PDT were identified. Over time, the frequency of PDT increased by 8.3%, whereas the proportion of patients submitted to PSURG declined (from 21.7% to 19.8%; P = 0.0004) and the percentage of patients submitted to non-operative management increased (from 56.7% to 59.1%; P = 0.01). In the Non-Op group, mortality decreased from 9.7% to 8.6% (P \u3c 0.001); morbidity and LoS remained unchanged at approximately 40% and approximately 12 days, respectively. In the PSURG group, mortality remained stable at approximately 15%, complications increased from 50.2% to 71.8% (P \u3c 0.0001) and LoS remained stable at approximately 21 days. For all PDT patients, significant independent predictors of mortality included: the presence of combined pancreatic and duodenal injuries; penetrating trauma, and age over 50 years. Having any operation (Any-Op) was associated with mortality, but PSURG was not a predictor of death. CONCLUSIONS: The utilization of operations for PDT has declined without affecting mortality, but operative morbidity increased significantly over the 12 years to 2009. The development of an evidence-based approach to invasive manoeuvres and an early multidisciplinary approach involving pancreatic surgeons may improve outcomes in patients with these morbid injuries

Centre volume and resource consumption in liver transplantation

BACKGROUND: Using SRTR/UNOS data, it has previously been shown that increased liver transplant centre volume improves graft and patient survival. In the current era of health care reform and pay for performance, the effects of centre volume on quality, utilization and cost are unknown. METHODS: Using the UHC database (2009-2010), 63 liver transplant centres were identified that were organized into tertiles based on annual centre case volume and stratified by severity of illness (SOI). Utilization endpoints included hospital and intensive care unit (ICU) length of stay (LOS), cost and in-hospital mortality. RESULTS: In all, 5130 transplants were identified. Mortality was improved at high volume centres (HVC) vs. low volume centres (LVC), 2.9 vs. 3.4%, respectively. HVC had a lower median LOS than LVC (9 vs. 10 days, P \u3c 0.0001), shorter median ICU stay than LVC and medium volume centres (MVC) (2 vs. 3 and 3 days, respectively, P \u3c 0.0001) and lower direct costs than LVC and MVC ($90,946 vs.$98,055 and $101,014, respectively, P \u3c 0.0001); this effect persisted when adjusted for severity of illness. CONCLUSIONS: This UHC-based cohort shows that increased centre volume results in improved long-term post-liver transplant outcomes and more efficient use of hospital resources thereby lowering the cost. A better understanding of these mechanisms can lead to informed decisions and optimization of the pay for performance model in liver transplantation