Fluid resuscitation in acute pancreatitis: Normal saline or lactated Ringer's solution?

AIM: To investigate whether administration of Ringer's solution(RL) could have an impact on the outcome of acute pancreatitis(AP).METHODS: We conducted a retrospective study on 103 patients [68 men and 35 women,mean age 51.2 years(range,19-92 years)] hospitalized between 2011 and 2012. All patients admitted to the Department of Gastroenterology of the Central Clinical Hospital of the Ministry of Interior(Poland) with a diagnosis of AP who had disease onset within 48 h of presentation were included in this study. Based on the presence of persistent organ failure(longer than 48 h) as a criterion for the diagnosis of severe AP(SAP) and the presence of local complications [diagnosis of moderately severe AP(MSAP)],patients were classified into 3 groups: mild AP(MAP),MSAP and SAP. Data were compared between the groups in terms of severity(using the revised Atlanta criteria) and outcome. Patients were stratified into 2 groups based on the type of fluid resuscitation: the 1-RL group who underwent standard fluid resuscitation with a RL 1000 m L solution or the 2-NS group who underwent standard fluid resuscitation with 1000 m L normal saline(NS). All patients from both groups received an additional 5% glucose solution(1000-1500 m L) and a multi-electrolyte solution(500-1000 m L).RESULTS: We observed 64(62.1%) patients with MAP,26(25.24%) patients with MSAP and 13(12.62%) patients with SAP. No significant difference in the distribution of AP severity between the two groups was found. In the 1-RL group,we identified 22(55.5%) MAP,10(25.5%) MSAP and 8(20.0%) SAP patients,compared with 42(66.7%) MAP,16(24.4%) MSAP and 5(7.9%) SAP cases in the 2-NS group(P = 0.187). The volumes of fluid administered during the initial 72-h period of hospitalization were similar among the patients from both the 1-RL and 2-NS groups(mean 3400 m L vs 3000 m L,respectively). No significant differences between the 1-RL and 2-NS groups were found in confirmed pancreatic necrosis [10 patients(25%) vs 12 patients(19%),respectively,P = 0.637]. There were no statistically significant differences between the 1-RL and 2-NS groups in the percentage of patients who required enteral nutrition(23 patients vs 17 patients,respectively,P = 0.534). Logistic regression analysis confirmed these findings(OR = 1.344,95%CI: 0.595-3.035,P = 0.477). There were no significant differences between the 1-RL and 2-NS groups in mortality and the duration of hospital stay(median of 9 d for both groups,P = 0.776).CONCLUSION: Our study failed to find any evidence that the administration of RL in the first days of AP leads to improved clinical outcomes.

MUC5AC/β-catenin expression and KRAS gene alteration in laterally spreading colorectal tumors

AIM： To clarify differences in mucin phenotype, prolif- erative activity and oncogenetic alteration among sub- types of colorectal laterally spreading tumor （LST）. METHODS： LSTs, defined as superficial elevated lesions greater than 10 mm in diameter with a low vertical axis, were macroscopically classified into two subtypes： （1） a granular type （Gr-LST） composed of superficially spread- ing aggregates of nodules forming a fiat-based lesion with a granulonodular and uneven surface; and （2） a non-granular type （NGr-LST） with a flat smooth surface and an absence of granulonodular formation. A total of 69 LSTs, comprising 36 Gr-LSTs and 33 NGr-LSTs, were immunohistochemically stained with MUC2, MUC5AC, MUC6, CD10 （markers of gastrointestinal cell lineage）, p53, 13-catenin and Ki-67 antibodies, and examined for alteration in exon 1 of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog （KRAS） and exon 15 of v-raf murine sarcoma viral oncogene homologue B1 （BRAF） by poly- merase chain reaction followed by direct sequencing. RESULTS： Histologically, 15 Gr-LST samples were ad- enomas with low-grade dysplasia （LGD）, 12 were high- grade dysplasia （HGD） and 9 were adenocarcinomas invading the submucosa （INV）, while 12 NGr-LSTs demonstrated LGD, 14 HGD and 7 INV. In the proximal colon, MUC5AC expression was significantly higher in the Gr-type than the NGr-type. MUC6 was expressed only in NGr-LST. MUC2 or CD10 did not differ. P53 ex- pression demonstrated a significant stepwise increment in progression through LGD-HGD-INV with both types of LST. Nuclear β-catenin expression was significantly higher in the NGr-type. Ki-67 expression was signifi- cantly higher in the Gr-type in the lower one third zone of the tumor. In proximal, but not distal colon tumors, the incidence of KRAS provided mutation was signifi- cantly higher in the Gr-type harboring a specific muta- tional pattern （G12V）. BRAF mutations （V600E） were detected only in two Gr-LSTs. CONCLUSION： The two subtypes of LST, especially in the proximal colon, have differing phenotypes of gastrointestinal cell lineage, proliferation and activa- tion of Wnt/β-catenin or RAS/RAF/extracellular signal- regulated kinase signaling.

Colorectal cancer screening

Colorectal cancer is a major public health burden worldwide. There is clear-cut evidence that screening will reduce colorectal cancer mortality and the only contentious issue is which screening tool to use. Most evidence points towards screening with fecal occult blood testing. The immunochemical fecal occult blood tests have a higher sensitivity than the guaiac-based tests. Zn addition, their automation and haemoglobin quantification allows a threshold for colonoscopy to be selected that can be accommodated within individual health care systems.

Variations and mutations in the hepatitis B virus genome and their associations with clinical characteristics

Hepatitis B virus(HBV) infection is major global issue, because chronic HBV infection is strongly associated with liver cancer. HBV spread worldwide with variousmutations and variations. This variability, called quasispecies, is derived from no proof-reading capacity of viral reverse transcriptase. So far, thousands of studies reported that the variety of genome is closely related to the geographic distribution and clinical characteristics. Recent technological advances including capillary sequencer and next generation sequencer have made in easier to analyze mutations. The variety of HBV genome is related to not only antigenicity of HBs-antigen but also resistance to antiviral therapies. Understanding of these variations is important for the development of diagnostic tools and the appropriate therapy for chronic hepatitis B. In this review, recent publications in relation to HBV mutations and variations are updated and summarized.

Necroptosis in inflammatory bowel disease and other intestinal diseases

Guo-Qiang XuFor a long time, it was believed that apoptosis and necrosis were the main pathways for cell death, but a growing body of research has shown that there are other pathways. Among these, necroptosis, a regulatory caspase-independent, programmed cell death pathway, is supposed to be of importance in the pathogenesis of many diseases. The mechanism of regulating, in-ducing and blocking necroptosis is a complex process that involves expression and regulation of a series of molecules including receptor interacting protein kinase 1 （RIPK1）, RIPK3, and mixed lineage kinase like protein. By blocking or downregulating expression of key molecules in the necroptotic pathway, intestinal inflammation can be affected to some extent. In this paper, we introduce the concept of necroptosis, its main pathway, and its impact on the pathogenesis ofinfammatory bowel disease （IBD） and other intestinal diseases, to explore new drug targets for intestinal diseases, including IBD.

Poorly expandable common bile duct with stones on endoscopic retrograde cholangiography

AIM： To describe characteristics of a poorly expandable （PE） common bile duct （CBD） with stones on en- doscopic retrograde cholangiography.METHODS： APE bile duct was characterized by a rigid and relatively narrowed distal CBD with retro- grade dilatation of the non-PE segment. Between 2003 and 2006, endoscopic retrograde cholangiography （ERC） images and chart reviews of 1213 patients with newly diagnosed CBD stones were obtained from the computer database of Therapeutic Endoscopic Centerin Chang Gung Memoria acteristic PE bile duct on Hospital. Patients with char ERC were identified from the database. Data of the patients as well as the safety and technical success of therapeutic ERC were collected and analyzed retrospectively.RESULTS： A total of 30 patients with CBD stones and characteristic PE segments were enrolled in this study. The median patient age was 45 years （range, 20 to 92 years）; 66.7% of the patients were men. The di ameters of the widest non-PE CBD segment, the PE segment, and the largest stone were 14.3 ± 4.9 mm, 5.8±1.6 mm, and 11.2±4.7 mm, respectively. The length of the PE segment was 39.7±15.4 mm （range, 12.3 mm to 70.9 mm）. To remove the CBD stone（s） completely, mechanical lithotripsy was required in 25 （83.3%） patients even though the stone size was not as large as were the difficult stones that have been described in the literature. The stone size and stone/ PE segment diameter ratio were associated with the need for lithotripsy. Post-ERC complications occurred in 4 cases： pancreatitis in 1, cholangitis in 2, and an im- pacted Dormia basket with cholangitis in 1. Two （6.7%） of the 28 patients developed recurrent CBD stones at follow-up （50±14 mo） and were successfully managed with therapeutic ERC.CONCLUSION： Patients with a PE duct frequently require mechanical lithotripsy for stones extraction, To retrieve stones successfully and avoid complications, these patients should be identified during ERC,

Proteomic and genomic studies of non-alcoholic fatty liver disease-clues in the pathogenesis

Non-alcoholic fatty liver disease(NAFLD)is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology.NAFLD is strongly associated with liver inflammation,metabolic hyperlipidaemia and insulin resistance.Frequently,NAFLD has been considered as the hepatic manifestation of metabolic syndrome.The pathophysiology of NAFLD has not been fully elucidated.Some patients can remain in the stage of simple steatosis,which generally is a benign condition;whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis,fibrosis,cirrhosis and hepatocellular carcinoma.The mechanism behind the progression is still not fully understood.Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD.Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patientdisease variations.Therefore,NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background.This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis.For proteomics section,this review highlighted functional proteins that involved in:(1)transportation;(2)metabolic pathway;(3)acute phase reaction;(4)antiinflammatory;(5)extracellular matrix;and(6)immune system.In the genomic studies,this review will discuss genes which involved in:(1)lipolysis;(2)adipokines;and(3)cytokines production.

m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment

AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection model.METHODS: C57BL/6 mice were subjected to a 70% partial hepatectomy(PH) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after PH with a combination of human recombinant interleukin 6(IL-6; 500 μg/kg per day) and hepatocyte growth factor(HGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after PH and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(LC3)-Ⅱ protein expression as a marker for autophagy. Hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical Center.RESULTS: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P < 0.01; 0.8% vs 1.4% at day 5, P = 0.02) and liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/L vs 185 U/L at day 2, P = 0.02). Expression of the autophagy marker LC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). Hepatic gene expression showed an increased inflammation-related response [tumor necrosis factor(TNF)-α 3.2-fold upregulation at day 2, P = 0.03; IL-1Ra 6.0-fold upregulation at day 2 and 42.3-fold upregulation at day 5, P < 0.01] and a reduced expression of cell cycle progression and angiogenesis-related factors(HGF 40% reduction at day 2; vascular endothelial growth factor receptor 2 50% reduction at days 2 and 5; angiopoietin 1 60% reduction at day 2, all P ≤ 0.01). Treatmentwith the regeneration stimulating cytokine IL-6 and growth factor HGF could overcome the inhibitory effect on liver weight(75% of initial total liver weight at day 3, P = 0.02 vs immunosuppression alone and P = 0.90 vs controls) and partially reversed gene expression changes caused by rapamycin(TNF-α and IL-1Ra levels at day 2 were restored to control levels). However, no significant changes in hepatocyte proliferation, serum injury markers or autophagy were found.CONCLUSION: mT OR inhibition severely impairs liver regeneration and increases autophagy after PH. These effects are partly reversed by stimulation of the IL-6 and HGF pathways.

Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions

AIM To investigate the main current etiologies of cirrhosis in Mexico.METHODS We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period(January 2012-December 2017). RESULTS A total of 1210 patients were included. The mean age was 62.5 years(SD = 12.1), and the percentages of men and women were similar(52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus(HCV)(36.2%), alcoholic liver disease(ALD)(31.2%), and nonalcoholic steatohepatitis(23.2%), and the least frequent were hepatitis B virus(1.1%), autoimmune disorders(7.3%), and other conditions(1.0%).CONCLUSION HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease(NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.

Review of experimental attempts of islet allotransplantation in rodents:Parameters involved and viability of the procedure

The purpose of the present study was to organize the parameters involved in experimental allotransplantation in rodents to elaborate the most suitable model to supply the scarcity of islet donors. We used the PubMed database to systematically search for published articles containing the keywords &#x0201c;rodent islet transplantation&#x0201d; to review. We included studies that involved allotransplantation experiments with rodents&#x02019; islets, and we reviewed the reference lists from the eligible publications that were retrieved. We excluded articles related to isotransplantation, autotransplantation and xenotransplantation, i.e., transplantation in other species. A total of 25 studies related to allotransplantation were selected for systematic review based on their relevance and updated data. Allotransplantation in rodents is promising and continues to develop. Survival rates of allografts have increased with the discovery of new immunosuppressive drugs and the use of different graft sites. These successes suggest that islet transplantation is a promising method to overcome the scarcity of islet donors and advance the treatment options for type 1 diabetes.

Magnetic Resonance Elastography for Liver Fibrosis in Methotrexate Treatment

Introduction: Hepatic magnetic resonance elastography (MRE) allows for noninvasive assessment of liver fibrosis. The purpose of this study was to evaluate the usefulness of MRE in detecting and quantifying liver fibrosis in patients with rheumatoid arthritis (RA) who have received methotrexate (MTX). Methods: The association between mean liver stiffness value as determined by MRE and variables of interest was determined. The decision for a liver biopsy in participants with an abnormal liver stiffness was made based on clinical judgment. Results: Sixty-five RA patients were enrolled. Mean liver stiffness value by MRE was abnormal in 7 patients, suggestive of hepatic injury. As a result of findings from the MRE, biopsies were performed in 5 patients and all correlated with elevated liver stiffness values. Elevated mean liver stiffness values were associated with body mass index (BMI) (OR = 1.18 per 1 kg/m2;95% CI: 1.03, 1.36;p = 0.017). Neither the total MTX dose nor the duration of MTX treatment was associated with mean liver stiffness value (p = 0.51 and P = 0.20, respectively). Conclusion: MRE provides a reliable, non-invasive assessment of liver fibrosis in patients with RA receiving MTX. Patients with RA receiving MTX who have an elevated BMI may be at increased risk for chronic hepatic injury, regardless of MTX cumulative dose or duration of treatment.