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Digestive System Diseases - Top 30 Publications

Update on anti-tumor necrosis factor agents and other new drugs for inflammatory bowel disease.

The treatment of inflammatory bowel disease (IBD)-ulcerative colitis (UC) and Crohn's disease (CD)-has evolved beyond surgery with the introduction of biologic agents, primarily antibodies against mediators of inflammation and cell attraction. Anti-tumor necrosis factor (TNF) agents have been the first line treatment for moderate to severe ulcerative colitis and Crohn's disease for more than 15 years. During that time much has been learnt about how best to use these agents. This review will assess the evidence on how to optimize the use of anti-TNF agents; when and how to start treatment; how to monitor treatment and when to de-escalate it; and the potential adverse effects of these drugs. New and emerging treatments such as anti-attractants, anti-interleukins, and Janus kinase (JAK) inhibitors will also be discussed.

Long non-coding RNA CASC2 regulates cell biological behaviour through the MAPK signalling pathway in hepatocellular carcinoma.

Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, especially cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in hepatocellular carcinoma have not been extensively studied. The long non-coding RNA CASC2 (cancer susceptibility candidate 2) has been characterised as a tumour suppressor in endometrial cancer and gliomas. However, the role and function of CASC2 in hepatocellular carcinoma remain unknown. In this study, using quantitative real-time polymerase chain reaction, we confirmed that CASC2 expression was downregulated in 50 hepatocellular carcinoma cases (62%) and in hepatocellular carcinoma cell lines compared with the paired adjacent tissues and normal liver cells. In vitro experiments further demonstrated that overexpressed CASC2 decreased hepatocellular carcinoma cell proliferation, migration and invasion as well as promoted apoptosis via inactivating the mitogen-activated protein kinase signalling pathway. Our findings demonstrate that CASC2 could be a useful tumour suppressor factor and a promising therapeutic target for hepatocellular carcinoma.

Role of CXCR4 and SDF1 as prognostic factors for survival and the association with clinicopathology in colorectal cancer: A systematic meta-analysis.

C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 were proven to play important roles in several types of cancer and in many biological processes connected with tumor growth, invasion, angiogenesis, and metastasis. However, the clinical significance of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 expression in colorectal cancer remains inaccurate. The purpose of this systematic meta-analysis is to investigate the role of C-X-C chemokine receptor type 4 and stromal cell-derived factor-1 as prognostic factors for survival and the association between C-X-C chemokine receptor type 4/ stromal cell-derived factor-1 and clinicopathology in colorectal cancer. Databases including PubMed, EMBASE, and Cochrane Library were searched for relevant literatures updated till January 2017. Review Manager 5.3 was used for data analysis. In our meta-analysis, C-X-C chemokine receptor type 4 expression is related to tumor-node-metastasis stage, tumor differentiation, liver metastasis, lymph node metastasis, distant metastasis, and diagnosis, and no correlation of C-X-C chemokine receptor type 4 expression with tumor size, gender, preoperative carcinoembryonic antigen, age, or vascular invasion has been observed. Stromal cell-derived factor-1 expression has no relationship with tumor-node-metastasis stage, lymph node metastasis, vascular invasion, age, gender, distant metastasis, or diagnosis. The expression of stromal cell-derived factor-1 has association with tumor differentiation. Moreover, the pooled hazard ratio for disease-free survival/overall survival showed that overexpression of C-X-C chemokine receptor type 4/stromal cell-derived factor-1 reduced disease-free survival/overall survival in colorectal cancer. Therefore, High expression of C-X-C chemokine receptor type 4/stromal cell-derived factor-1 which is essential in tumor progression can predict poor survival that may provide more advance prognostic clues to colorectal cancer patients.

Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better than alpha-fetoprotein in diagnosis of hepatitis B virus-related hepatocellular carcinoma patients.

PTEN: A potential prognostic marker in virus-induced hepatocellular carcinoma.

PTEN is the second most frequently mutated tumor suppresser gene in cancers after p53. Genetic and epigenetic alterations in the PTEN gene and its regulatory regions have been reported in various studies. PTEN is a crucial downregulator of the pro-survival phosphoinositide 3-kinase/Akt/mammalian target of rapamycin pathway and also suppresses insulin signaling. Failure to regulate these pathways leads to increase in cell proliferation and migration which in turn promotes tumorigenesis. PTEN underexpression is mediated by a variety of cytokines and stress kinases which seem to collectively induce the RAS/mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway. In the context of hepatocellular carcinoma, reduced expression of PTEN is seen in nearly half of the cases on average. In some cases, PTEN has been observed to be either mutated or methylated which can also lead to reduced expression or in some cases, complete loss of expression. On the cellular level, PTEN is also a target in the pathogenic pathway of hepatitis C virus core protein and hepatitis B virus X protein. These viruses appear to alter PTEN regulation and pro-apoptotic ability to enhance the process of tumor formation. In perspective of the crucial role PTEN plays in balancing proliferation and apoptosis, we propose PTEN as a valuable marker in the diagnosis, assessment of tumor grade, and disease stage in hepatocellular carcinoma patients.

Decreased expression of MGMT in correlation with aberrant DNA methylation in esophageal cancer patients from North India.

O-6-methylguanine-DNA methyltransferase, DNA repair gene, has been found to be involved with the pathogenesis of the esophageal cancer. DNA hypermethylation and other factors have been suggested to downregulate O-6-methylguanine-DNA methyltransferase. In this communication, the methylation status of O-6-methylguanine-DNA methyltransferase gene and the corresponding O-6-methylguanine-DNA methyltransferase protein expression in esophageal cancer from North India has been studied. In all, 80 samples of tumor tissue along with adjacent normal tissue as controls were analyzed for messenger RNA level of O-6-methylguanine-DNA methyltransferase gene, protein expression, and subcellular localization. The messenger RNA expression was studied using real-time quantitative polymerase chain reaction, protein expression, and its subcellular localization by Western blotting and immunohistochemistry. DNA methylation was assessed through methylation-specific polymerase chain reaction. Clinicopathological parameters were recorded and correlated with the O-6-methylguanine-DNA methyltransferase expression. O-6-methylguanine-DNA methyltransferase messenger RNA expression was found to be downregulated in 65% cases (52/80). The expression of O-6-methylguanine-DNA methyltransferase at the protein level was also found to be absent in 65% (52/80) cases. In all, 52 cases had low or no expression of the protein, whereas out of those 28 remaining cases, 11.25% (09/80) cases had high O-6-methylguanine-DNA methyltransferase protein expression. The absence of O-6-methylguanine-DNA methyltransferase protein coincided with the methylated cases in 84% (38/45), whereas in 07 cases, out of the 45 methylated, O-6-methylguanine-DNA methyltransferase protein was present. The aggressive esophageal cancer patients having methylated O-6-methylguanine-DNA methyltransferase had more than 50% cases with no/mild expression of the O-6-methylguanine-DNA methyltransferase protein ( p > 0.001). Loss of O-6-methylguanine-DNA methyltransferase protein was very frequent in the incidence of esophageal cancer from North Indian patients, and methylation of the promoter region of O-6-methylguanine-DNA methyltransferase was significantly associated in its downregulation.

Development and validation of risk prediction equations to estimate survival in patients with colorectal cancer: cohort study.

Objective To develop and externally validate risk prediction equations to estimate absolute and conditional survival in patients with colorectal cancer. Design Cohort study.Setting General practices in England providing data for the QResearch database linked to the national cancer registry.Participants 44 145 patients aged 15-99 with colorectal cancer from 947 practices to derive the equations. The equations were validated in 15 214 patients with colorectal cancer from 305 different QResearch practices and 437 821 patients with colorectal cancer from the national cancer registry.Main outcome measures The primary outcome was all cause mortality and secondary outcome was colorectal cancer mortality.Methods Cause specific hazards models were used to predict risks of colorectal cancer mortality and other cause mortality accounting for competing risks, and these risk estimates were combined to obtain risks of all cause mortality. Separate equations were derived for men and women. Several variables were tested: age, ethnicity, deprivation score, cancer stage, cancer grade, surgery, chemotherapy, radiotherapy, smoking status, alcohol consumption, body mass index, family history of bowel cancer, anaemia, liver function test result, comorbidities, use of statins, use of aspirin, clinical values for anaemia, and platelet count. Measures of calibration and discrimination were determined in both validation cohorts at 1, 5, and 10 years.Results The final models included the following variables in men and women: age, deprivation score, cancer stage, cancer grade, smoking status, colorectal surgery, chemotherapy, family history of bowel cancer, raised platelet count, abnormal liver function, cardiovascular disease, diabetes, chronic renal disease, chronic obstructive pulmonary disease, prescribed aspirin at diagnosis, and prescribed statins at diagnosis. Improved survival in women was associated with younger age, earlier stage of cancer, well or moderately differentiated cancer grade, colorectal cancer surgery (adjusted hazard ratio 0.50), family history of bowel cancer (0.62), and prescriptions for statins (0.77) and aspirin (0.83) at diagnosis, with comparable results for men. The risk equations were well calibrated, with predicted risks closely matching observed risks. Discrimination was good in men and women in both validation cohorts. For example, the five year survival equations on the QResearch validation cohort explained 45.3% of the variation in time to colorectal cancer death for women, the D statistic was 1.86, and Harrell's C statistic was 0.80 (both measures of discrimination, indicating that the scores are able to distinguish between people with different levels of risk). The corresponding results for all cause mortality were 42.6%, 1.77, and 0.79.Conclusions Risk prediction equations were developed and validated to estimate overall and conditional survival of patients with colorectal cancer accounting for an individual's clinical and demographic characteristics. These equations can provide more individualised accurate information for patients with colorectal cancer to inform decision making and follow-up.

The expression profiling of serum miR-92a, miR-375, and miR-760 in colorectal cancer: An Egyptian study.

Dysregulation in microRNA expression is a common feature in colorectal cancer. Due to the inconsistent results regarding serum miR-92a expression pattern and the insufficient studies on serum miR-375 and miR-760, we aimed in this study to investigate their expression profile and diagnostic and prognostic power in Egyptian colorectal cancer patients. The expression profile of miR-92a, miR-375, and miR-760 was determined in the sera of 64 colorectal cancer patients using quantitative real-time reverse transcription polymerase chain reaction in comparison to 27 healthy control subjects. The expression fold change of the studied microRNAs was correlated with patients' clinicopathological features. Receiver operating characteristic curve analysis was done to determine the role of these microRNAs in colorectal cancer diagnosis and follow-up according to the yielded area under the curve. The expression pattern of miR-92a was significantly upregulated (3.38 ± 2.52, p < 0.0001), while both of miR-375 and 760 were significantly downregulated (-1.250 ± 1.80, p< 0.0001; -1.710 ± 1.88, p < 0.0001, respectively) in colorectal cancer than the control. MiR-92a was positively correlated ( r = 0.671, p = 0.0001), while miR-375 and miR-760 were inversely correlated ( r = -0.414, p = 0.001; r = -0.644, p = 0.0001) with advanced colorectal cancer stages. Receiver operating characteristic curve analysis disclosed the highest diagnostic potential for miR-760 to discriminate colorectal cancer patients and early-stage colorectal cancer from the control (area under the curve = 0.922 and 0.875, respectively), while the highest prognostic potential for discrimination between colorectal cancer stages was for miR-92a. In conclusion, serum level of miR-92a, miR-375, and miR-760 may serve as biomarkers of colorectal cancer in Egyptian patients with high diagnostic power for miR-760 and high prognostic power for miR-92a.

Molecular interplay of pro-inflammatory transcription factors and non-coding RNAs in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is the sixth most common cancer in the developing world. The aggressive nature of esophageal squamous cell carcinoma, its tendency for relapse, and the poor survival prospects of patients diagnosed at advanced stages, represent a pressing need for the development of new therapies for this disease. Chronic inflammation is known to have a causal link to cancer pre-disposition. Nuclear factor kappa B and signal transducer and activator of transcription 3 are transcription factors which regulate immunity and inflammation and are emerging as key regulators of tumor initiation, progression, and metastasis. Although these pro-inflammatory factors in esophageal squamous cell carcinoma have been well-characterized with reference to protein-coding targets, their functional interactions with non-coding RNAs have only recently been gaining attention. Non-coding RNAs, especially microRNAs and long non-coding RNAs demonstrate potential as biomarkers and alternative therapeutic targets. In this review, we summarize the recent literature and concepts on non-coding RNAs that are regulated by/regulate nuclear factor kappa B and signal transducer and activator of transcription 3 in esophageal cancer progression. We also discuss how these recent discoveries can pave way for future therapeutic options to treat esophageal squamous cell carcinoma.

Immunohistochemical Profile of Tumor Pathways and Prognostic Significance in Colon Adenocarcinomas.

The current study examined the immunohistochemical expression levels of molecules on carcinogenesis pathway and evaluated their clinicopathologic significance in colorectal adenocarcinoma (CRA). A total of 189 CRA and 20 colonic mucosal tissue samples were evaluated by immunohistochemical staining using 38 antibodies targeting the known molecules that play roles in developmental pathways of various tumors. The immunoexpression data of the patients were compared to clinicopathologic parameters. Expression loss of MLH1, MSH2, MSH6, PMS2, PTEN, Smad4 and E-cadherin, and overexpression of ALDH1, CD44, CAIX, P504S (AMACR), TGFΒ, and ZEB1 were statistically significant in CRA compared to normal colon mucosa. Long-term clinical follow-up findings in our cases suggested that AMACR, CAIX, ALDH1, TGFΒ, ZEB1 overexpression, and cyclinD1, p53, E-cadherin, and PTEN inactivity might be useful markers of a poor prognosis in CRA. In survival analyses, the expression of CAIX and AMACR were significantly associated with overall survival in both the univariate and multivariate analyses (log-rank test; p < 0.01 and p < 0.05, respectively).

Impact of High Altitude on Clinicopathological Features and Prognosis after R0 Resection for Gastric Cancer: A Population-Based Multicenter Study.

Geographic variation has an important role in both carcinogenesis and prognosis of gastric cancer (GC). High altitude is a special hypoxic environment that is also correlated with the occurrence of GC. Different onset features and prognoses of GC in high altitude with respect to plains are rarely reported and remain unknown. This multicenter study compared different clinicopathological characteristics and prognoses of patients with resected GC who were from locations of both high altitudes and plains in China. From December 2009 to December 2011, patients with resected GC were retrospectively recruited at four centers located at high altitudes and the plains. Clinicopathological data were analyzed to explore the differences between the two groups. The Cox proportional-hazards model was used to investigate the prognostic factors for GC and estimate the independent impact of altitude on long-term survival after adjusting for covariates. Noncardia GC, from a moderate to well tumor grade, was more common in patients from high altitudes. Moreover, a higher proportion of moderate to well and moderate tumor grade and younger age of onset was found in patients with noncardia GC coming from high altitudes. Different overall survival (OS) presented in noncardia GC rather than cardia GC, with 69.94% GC-related 3-yr OS in high altitude versus 75.23% in the plains. High altitude was confirmed as a significant prognostic factor for noncardia GC (the hazard ratio for high altitude vs. plains was 1:50, with a 95% confidence interval; 1.06-1.82, p = 0.018) through a multivariate Cox proportional-hazards model analysis. This prognostic value was independent of all other factors. High altitude has an important role in clinicopathological features and prognosis of GC. Improvements in GC diagnosis and management at high altitudes are urgently needed.

Pediatric Hepatobiliary Neoplasms: An Overview and Update.

Recent developments regarding the treatment of pediatric liver tumors have significantly improved patient care. Stimulated by collaboration between international pediatric groups, advances have been made in surgical techniques, transplantation options, and chemotherapy schemas. In light of this progress, clear understanding of the state-of-the-art imaging evaluation of hepatobiliary tumors has become even more integral to the effective management of children with hepatic neoplasms. The unique imaging features of hepatic neoplasms in the pediatric population, when coupled with supportive demographic data and laboratory findings, can lead to accurate diagnosis and proper treatment of hepatobiliary tumors.

Neonatal Gastrointestinal Emergencies: Step-by-Step Approach.

Neonatal gastrointestinal emergencies are caused by a diverse set of primarily congenital entities that may affect the upper or lower gastrointestinal tracts, and occasionally both. Although a diagnosis can sometimes be made on prenatal imaging, more commonly patients present after birth and require prompt diagnosis to facilitate timely treatment. Imaging plays a central role in the accurate diagnosis of these entities and typically consists of an initial abdominal series followed by either an upper gastrointestinal series or contrast enema. The authors review the most common neonatal gastrointestinal emergencies and provide a step-by-step approach to the accurate imaging diagnosis.

MicroRNA-630 Suppresses Epithelial-to-Mesenchymal Transition by Regulating FoxM1 in Gastric Cancer Cells.

In the present study, we investigated the functional role of microRNA (miR)-630 in epithelial-to-mesenchymal transition (EMT) of gastric cancer (GC) cells, as well as the regulatory mechanism. Cells of human GC cell line SGC 7901 were transfected with miR-630 mimic or miR-630 inhibitor. The transfection efficiency was confirmed by qRT-PCR. Cell migration and invasion were determined by Transwell assay. Protein expression of E-cadherin, vimentin, and Forkhead box protein M1 (FoxM1) was tested by Western blot. Moreover, the expression of FoxM1 was elevated or suppressed, and then the effects of miR-630 abnormal expression on EMT and properties of migration and invasion were examined again, as well as protein expression of Ras/phosphoinositide 3-kinase (PI3K)/AKT related factors. The results showed that (i) the EMT and properties of migration and invasion were statistically decreased by overexpression of miR-630 compared to the control group but markedly increased by suppression of miR-630. However, (ii) abnormal expression of FoxM1 reversed these effects in GC cells. Moreover, (iii) expression of GTP-Rac1, p-PI3K, and p-AKT was decreased by miR-630 overexpression but increased by FoxM1 overexpression. (iv) The decreased levels of GTP-Rac1, p-PI3K, and p-AKT induced by miR-630 overexpression were dramatically elevated by simultaneous overexpression of FoxM1. In conclusion, our results suggest that miR-630 might be a tumor suppressor in GC cells. MiR-630 suppresses EMT by regulating FoxM1 in GC cells, supposedly via inactivation of the Ras/PI3K/AKT pathway.

Role of Na+/K(+)-ATPase in Natriuretic Effect of Prolactin in a Model of Cholestasis of Pregnancy.

Participation of Na+/K+-ATPase in the natriuretic effect of prolactin in a cholestasis of pregnancy model was investigated. The Na+/K+-ATPase activity in rat kidney medulla, where active sodium reabsorption occurs, decreased in the model of cholestasis of pregnancy and other hyperprolactinemia types compared with intact animals. This effect was not connected with the protein level of α1- and β-subunits of Na+/K+-ATPase measured by Western blotting in the kidney medulla. Decrease in Na+/K+-ATPase activity in the kidney cortex was not significant, as well as decrease in the quantity of mRNA and proteins of the α1- and β-subunits of Na+/K+-ATPase. There were no correlations between the Na+/K+-ATPase activity and sodium clearance, although sodium clearance increased significantly in the model of cholestasis of pregnancy and other hyperprolactinemia groups under conditions of stable glomerular filtration rate measured by creatinine clearance. We conclude that the Na+/K+-ATPase is not the only mediator of the natriuretic effect of prolactin in the model of cholestasis of pregnancy.

Acute Lower Gastrointestinal Bleeding.

Acute Lower Gastrointestinal Bleeding.

Irritable Bowel Syndrome.

This issue provides a clinical overview of irritable bowel syndrome, focusing on diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.

Synergistic protective effect of picrorhiza with honey in acetaminophen induced hepatic injury.

Rhizome of picrorhiza along with honey prevents hepatic damage and cure the acetaminophen (paracetamol) induced hepatotoxicity by modulating the activity of hepatic enzymes. Here, we studied the in vivo effects of Picrorhiza kurroa and honey on acetaminophen induced hepatotoxicity Balb/c mice model. Hepatic histopathological observations of acetaminophen fed (day-6) group showed more congestion, hemorrhage, necrosis, distorted hepatic architecture and nuclear inclusion. Such damages were recompensed to normal by picrorhiza or honey alone or both in combinations. We observed increased activity of SGPT and SGOT in injured liver tissues, and that too was compensated to normal with picrorhiza or honey alone or both in combinations. We observed 1.27 and 1.23-fold enhanced activity of SGPT in serum and liver lysate, respectively while SGOT showed 1.66 and 1.11 fold enhanced activity. These two enzymes are signature enzymes of liver damage. Thus, our results support that honey may be used with drug picrorhiza due to its synergistic role to enhance hepatoprotective and hepatoregenerative ability along with allopathic drugs to mitigate the hepatotoxic effects.

Diagnosis and management of inflammatory bowel disease in children.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are lifelong conditions that often begin in childhood. The implications of IBD are of particular importance in children because of the potential negative effects on growth, development, psychosocial function, and overall wellbeing. The key management strategy is to achieve sustained control of intestinal inflammation and monitor for potential complications of the disease and side effects of therapies. Overall, the evidence on the management of IBD in children is less extensive than in adults, but good quality multicenter studies and various guidelines and society consensus statements are available. This review summarizes the evidence on the pathophysiology, diagnosis, and approaches to management of children and adolescents with IBD.

Histologic Remission following Neoadjuvant Immunotherapy in a Patient with Lynch-Syndrome and Primarily Unresectable Relapse of Rectum Carcinoma.

Clinical History A 43-year-old male patient was diagnosed to have rectum carcinoma cT4N2M0 with underlying Lynch-Syndrome. After initializing neoadjuvant radio-chemotherapy followed by operation, the patient presents with an extensive locoregional relapse within a short time. In order to achieve resectability, a second line treatment with FOLFOXIRI protocol in addition to Bevacizumab was conducted. However, after completing six cycles of this intensiv treatment protocol, the tumour showed further progression. Clinical Course Having no evidence of distance metastasis, we decided to initiate off-label use of Pembrolizumab, a PD-1-receptor inhibitor. Clinical symptoms decreased rapidly and after receiving six cycles, PET/CT imaging showed regression. The side effects were limited to subclinical autoimmune thyroiditis. After re-operation no evidence of malignancy were found in the resectates of exenteration of the pelvis. Currently the patient is capable of working with only limited symptoms. Conclusion Pembrolizumab offers new treatment options for patients with DNA-repair-deficiency mismatch, e. g. Lynch-Syndrome. A phase II study already showed effectiveness in this particular group of patients. The striking and unexpected histo-pathologic results showing full remission should draw attention to the use of Pembrolizumab in neoadjuvant settings.

Dysphagia after Occipitocervical Fusion.

Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection.

Patients who are chronically infected with hepatitis C virus (HCV) and who do not have a sustained virologic response after treatment with regimens containing direct-acting antiviral agents (DAAs) have limited retreatment options.

Excess intraoperative fluid volume administration is associated with pancreatic fistula after pancreaticoduodenectomy: A retrospective multicenter study.

Recent studies on perioperative fluid administration in patients undergoing pancreaticoduodenectomy (PD) have suggested that increased fluid loads are associated with worse perioperative outcomes. The purpose of this study was to investigate the relationship between intraoperative fluid (IOF) administration and postoperative pancreatic fistula (POPF), and to determine additional risk factors affecting pancreatic fistula in patients undergoing PD.From 2005 to 2014, a total of 182 patients with various periampullary diseases after PD were reviewed retrospectively at Dongguk University Ilsan Hospital, Chung-Ang University Hospital, and Dongnam Institute of Radiological and Medical Sciences. Patients were assigned to high or low IOF groups based on more or less fluid administration for supplementation of estimated blood loss and maintenance volume (12.5 mL/kg/h) than planned, respectively. The associations between IOF administration, pancreatic fistula development, and perioperative outcomes were evaluated.A total of 98 patients were assigned to the high-IOF group, and 84 to the low-IOF group. Risk factors for pancreatic fistula after univariate analysis were assignment to the high-IOF group, higher preoperative serum hemoglobin level, ampullary or bile duct cancer, pylorus preserving PD, small pancreatic duct, duct-to-mucosa pancreatojejunostomy, use of a stent, and mesh application to pancreatojejunal anastomosis. Among these, assignment to the high-IOF group (hazard ratio [HR] = 5.501, 95% CI 1.624-18.632, P = .006) and a small (<4 mm) pancreatic duct (HR = 4.129, 95% CI 1.569-14.658, P = .035) were identified as independent risk factors for the development of pancreatic fistula after multivariate analysis. However, long-term survival rate did not differ according to IOF group or duct size.Excessive IOF volume administration is associated with an increased incidence of pancreatic fistula after pancreaticoduodenectomy.

Widely differing screening and treatment practice for osteoporosis in patients with inflammatory bowel diseases in the Swiss IBD cohort study.

Low bone mineral density (BMD) and osteoporosis remain frequent problems in patients with inflammatory bowel diseases (IBDs). Several guidelines with nonidentical recommendations exist and there is no general agreement regarding the optimal approach for osteoporosis screening in IBD patients. Clinical practice of osteoporosis screening and treatment remains insufficiently investigated.In the year 2014, a chart review of 877 patients included in the Swiss IBD Cohort study was performed to assess details of osteoporosis diagnostics and treatment. BMD measurements, osteoporosis treatment, and IBD medication were recorded.Our chart review revealed 253 dual-energy x-ray absorptiometry (DXA) scans in 877 IBD patients; osteoporosis was prevalent in 20% of tested patients. We identified widely differing osteoporosis screening rates among centers (11%-62%). A multivariate logistic regression analysis identified predictive factors for screening including steroid usage, long disease duration, and perianal disease; even after correction for all risk factors, the study center remained a strong independent predictor (odds ratio 2.3-21 compared to the center with the lowest screening rate). Treatment rates for patients with osteoporosis were suboptimal (55% for calcium, 65% for vitamin D) at the time of chart review. Similarly, a significant fraction of patients with current steroid medication were not treated with vitamin D or calcium (treatment rates 53% for calcium, 58% for vitamin D). For only 29% of patients with osteoporosis bisphosphonate treatment was started. Treatment rates also differed among centers, generally following screening rates. In patients with longitudinal DXA scans, calcium and vitamin D usage was significantly associated with improvement of BMD over time.Our analysis identified inconsistent usage of osteoporosis screening and underuse of osteoporosis treatment in IBD patients. Increasing awareness of osteoporosis as a significant clinical problem in IBD patients might improve patient care.

Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile.

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1-4.3%, P = 6×10-27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data.

Irritable Bowel Syndrome.

: Irritable bowel syndrome (IBS) is a common, chronic gastrointestinal (GI) condition characterized by disturbances in bowel habits and abdominal pain in the absence of known organic pathology. IBS reduces quality of life and is costly to treat. It is diagnosed using the symptom-based Rome criteria for functional GI disorders, which was recently updated and released as Rome IV. Both physiologic and psychological variables play a role in the etiology of IBS and perpetuate symptoms. Although research has shed light on IBS pathophysiology, therapeutic interventions remain symptom driven, employing both pharmacologic and nonpharmacologic approaches. Here, the authors review the epidemiology and pathophysiology of IBS, summarize diagnostic and treatment strategies, and discuss implications for nursing practice.

Surgical outcomes of different approaches to esophageal replacement in long-gap esophageal atresia: A systematic review.

Esophageal replacement (ER) surgery has been widely used in long-gap esophageal atresia (LGEA) over the past few decades. The most commonly used surgical approaches in many pediatric surgical centers include colon interposition (CI), gastric pull-up (GPU), jejunal interposition (JI), and gastric tube reconstruction (GTR). However, there is no systematic evidence on which is the optimal conduit for the native esophagus. The aim of this systematic review was to evaluate the short- and long-term outcomes among these 4 replacement approaches in LGEA cases based on current evidence.

Effect of laparoscopic gastrectomy on compliance with adjuvant chemotherapy in patients with gastric cancer.

This study was designed to investigate the effect of laparoscopic gastrectomy on adjuvant chemotherapy in patients with gastric cancer.Patients with gastric cancer who underwent radical gastrectomy at our institution from January 2008 to January 2015 with R0 resection, as determined by a pathological examination, were included in this study. According to the surgical approach, patients were divided into the laparoscopic gastrectomy (LG) group and open gastrectomy (OG) group. Short-term and long-term outcomes were compared between the 2 groups.Of the 206 patients enrolled in the study, 114 patients were included in the LG group and 92 patients were included in the OG group. There was no significant difference in patients' general data, including age, sex, medical comorbidities, and pathological staging, between the 2 groups. However, patients in the LG group had less intraoperative blood loss, fewer postoperative complications, and a shorter hospital stay compared with patients in the OG group. There was no significant difference in the start time of adjuvant chemotherapy between the groups. However, compared with OG, LG had the following advantages: patients received more cycles of adjuvant chemotherapy, more patients received a full dose of on-schedule adjuvant chemotherapy, and more patients completed ≥75% of the planned dose. Long-term survival and disease-free survival rates were higher in the LG than in the OG.In summary, LG can improve compliance with adjuvant chemotherapy and long-term outcomes in patients with gastric cancer.

Identifying miRNA-mRNA regulation network of chronic pancreatitis based on the significant functional expression.

The aim of this study was to explore the underlying molecular mechanism and potential molecular biomarkers of chronic pancreatitis (CP) and construct a miRNA-mRNA regulation network.