Restoring homeostasis of CD4^+ T cells in hepatitis-B-virusrelated liver fibrosis

Immune-mediated liver injury is widely seen during hepatitis B virus(HBV) infection. Unsuccessful immune clearance of HBV results in chronic hepatitis and increases the risk of liver cirrhosis and hepatocellular carcinoma. HBV-related liver fibrosis(HBVLF),occurring as a result of HBV-induced chronic hepatitis,is a reversible,intermediate stage of chronic hepatitis B(CHB) and liver cirrhosis. Therefore,defining the pathogenesis of HBVLF is of practical significance for achieving better clinical outcomes. Recently,the homeostasis of CD4+ T cells was considered to be pivotal in the process of HBVLF. To better uncover the underlying mechanisms,in this review,we systematically retrospect the impacts of different CD4+T-cell subsets on CHB and HBVLF. We emphasize CD4+ T-cell homeostasis and the important balance between regulatory T(Treg) and T helper 17(Th17) cells. We discuss some cytokines associated with Treg and Th17 cells such as interleukin(IL)-17,IL-22,IL-21,IL-23,IL-10,IL-35 and IL-33,as well as surface molecules such as programmed cell death protein 1,cytotoxic T lymphocyte-associated antigen 4,T cell immunoglobulin domain and mucin domain-containing molecule 3 and cannabinoid receptor 2 that have potential therapeutic implications for the homeostasis of CD4+ T cells in CHB and HBVLF.

Pancreatic fluid collections: What is the ideal imaging technique?

Pancreatic fluid collections(PFCs) are seen in up to 50% of cases of acute pancreatitis. The Revised Atlanta classification categorized these collections on the basis of duration of disease and contents, whether liquid alone or a mixture of fluid and necrotic debris. Management of these different types of collections differs because of the variable quantity of debris; while patients with pseudocysts can be drained by straight-forward stent placement, walledoff necrosis requires multi-disciplinary approach. Differentiating these collections on the basis of clinical severity alone is not reliable, so imaging is primarily performed. Contrast-enhanced computed tomography is the commonly used modality for the diagnosis and assessment of proportion of solid contents in PFCs; however with certain limitations such as use of iodinated contrast material especially in renal failure patients and radiation exposure. Magnetic resonance imaging(MRI) performs better than computed tomography(CT) in characterization of pancreatic/peripancreatic fluid collections especially for quantification of solid debris and fat necrosis(seen as fat density globules), and is an alternative in those situations where CT is contraindicated. Also magnetic resonance cholangiopancreatography is highly sensitive for detecting pancreatic duct disruption and choledocholithiasis. Endoscopic ultrasound is an evolving technique with higher reproducibility for fluid-to-debris component estimation with the added advantage of being a single stage procedure for both diagnosis(solid debris delineation) and management(drainage of collection) in the same sitting. Recently role of diffusion weighted MRI and positron emission tomography/CT with ^(18)F-FDG labeled autologous leukocytes is also emerging for detection of infection noninvasively. Comparative studies between these imaging modalities are still limited. However we look forward to a time when this gap in literature will be fulfilled.

Endoscopic treatments for small gastric subepithelial tumors originating from muscularis propria layer

Minimally invasive endoscopic resection has become an increasingly popular method for patients with small(less than 3.5 cm in diameter) gastric subepithelial tumors(SETs) originating from the muscularis propria(MP) layer. Currently, the main endoscopic therapies for patients with such tumors are endoscopic muscularis excavation, endoscopic full-thickness resection, and submucosal tunneling endoscopic resection. Although these endoscopic techniques can be used for complete resection of the tumor and provide an accurate pathological diagnosis, these techniques have been associated with several negative events, such as incomplete resection, perforation, and bleeding. This review provides detailed information on the technical details, likely treatment outcomes, and complications associated with each endoscopic method for treating/removing small gastric SETs that originate from the MP layer.

I_κB kinase-beta inhibitor attenuates hepatic fibrosis in mice

AIM: To investigate the anti-fibrosis effect of IκB kinase-beta inhibitor (IKK2 inhibitor IMD0354) in liver fibrosis. METHODS: Twenty male C57BL6 mice were divided into four groups. Five high-fat fed mice were injected with lipopolysaccharide (LPS, 10 mg/kg) intraperitoneally and five high-fat fed mice were without LPS injection to build models of liver injury, and the intervention group (five mice) was injected intraperitoneally with IKK2 inhibitor (IMD 30 mg/kg for 14 d), while the remaining five mice received a normal diet as controls. Hepatic function, pathological evaluation and liver interleukin-6 (IL-6) expression were examined. Western blotting and real-time polymerase chain reaction were used to detect the expressions of nuclear factor-κB (NF-κB), alpha-smooth muscle actin (α-SMA), tumor growth factor-beta1 (TGF-β1), tumor necrosis factor-alpha (TNF-α), typeⅠand type Ⅲ collagen proteins and mRNA. RESULTS: A mouse model of liver injury was successfully established, and IMD decreased nuclear transloca-tion of NF-κB p65 in liver cells. In the IMD-treated group, the levels of alanine aminotransferase (103 ± 9.77 μ/L vs 62.4 ± 7.90 μ/L, P < 0.05) and aminotransferase (295.8 ± 38.56 μ/L vs 212 ± 25.10 μ/L, P < 0.05) were significantly decreased when compared with the model groups. The histological changes were significantly ameliorated. After treatment, the expressions of IL-6 (681 ± 45.96 vs 77 ± 7.79, P < 0.05), TGF-β1 (Western blotting 5.65% ± 0.017% vs 2.73% ± 0.005%, P < 0.05), TNF-α (11.58% ± 0.0063% vs 8.86% ± 0.0050%, P < 0.05), typeⅠcollagen (4.49% ± 0.014% vs 1.90% ± 0.0006%, P < 0.05) and type Ⅲ collagen (3.46% ± 0.008% vs 2.29% ± 0.0035%, P < 0.05) as well as α-SMA (6.19 ± 0.0036 μ/L vs 2.16 ± 0.0023 μ/L, P < 0.05) protein and mRNA were downregulated in the IMD group compared to the fibrosis control groups (P < 0.05). CONCLUSION: IKK2 inhibitor IMD markedly improved non-alcoholic fatty liver disease in mice by lowering NF-κB activation, which could become a remedial target for liver fibrosis.

Propofol vs traditional sedative agents for endoscopic retrograde cholangiopancreatography:A meta-analysis

AIM:To investigate the efficacy and safety of propofol sedation for endoscopic retrograde cholangiopancreatography(ERCP).METHODS:Databases including PubMed,Embase,and the Cochrane Central Register of Controlled Trials updated as of October 2010 were searched.Main outcome measures were ERCP procedure duration,recovery time,incidence of hypotension and hypoxia.RESULTS:Six trials with a total of 663 patients were included.The pooled mean difference in ERCP procedure duration between the propofol and traditional sedative agents was-8.05(95%CI:-16.74 to 0.63),with no significant difference between the groups.Thepooled mean difference in the recovery time was-18.69(95%CI:-25.44 to-11.93),which showed a significant reduction with use of propofol sedation.Compared with traditional sedative agents,the pooled OR with propofol sedation for ERCP causing hypotension or hypoxia was 1.69(95%CI:0.82-3.50)and 0.90(95%CI:0.55-1.49),respectively,which indicated no significant difference between the groups.CONCLUSION:Propofol sedation during ERCP leads to shorter recovery time without an increase of cardiopulmonary side effects.Propofol sedation can provide adequate sedation during ERCP.

Psychological controversies in gastroparesis: A systematic review

AIM To systematically review literature addressing three key psychologically-oriented controversies associated with gastroparesis. METHODS A comprehensive search of Pub Med, CINAHL, and PsycI NFO databases was performed to identify literature addressing the relationship between gastroparesis and psychological factors. Two researchers independently screened all references. Inclusion criteria were: an adult sample of gastroparesis patients, a quantitative methodology, and at least one of the following:(1) evaluation of the prevalence of psychopathology;(2) an outcome measure of anxiety, depression, or quality of life; and(3) evidence of a psychological intervention. Case studies, review articles, and publications in languages other than English were excluded from the current review. RESULTS Prevalence of psychopathology was evaluated by three studies(n = 378), which found that combined anxiety/depression was present in 24% of the gastroparesis cohort, severe anxiety in 12.4%, depression in 21.8%-23%, and somatization in 50%. Level of anxiety and depression was included as an outcome measure in six studies(n = 1408), and while limited research made it difficult to determine the level of anxiety and depression in the cohort, a clear positive relationship with gastroparesis symptom severity was evident.Quality of life was included as an outcome measure in 11 studies(n = 2076), with gastroparesis patients reporting lower quality of life than population norms, and a negative relationship between quality of life and symptom severity. One study assessed the use of a psychological intervention for gastroparesis patients(n = 120) and found that depression and gastric function were improved in patients who received psychological intervention, however the study had considerable methodological limitations. CONCLUSION Gastroparesis is associated with significant psychological distress and poor quality of life. Recommendations for future studies and the development of psychological interventions are provided.

Efficacy of S-1 vs capecitabine for the treatment of gastric cancer: A meta-analysis

AIM: To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.METHODS: MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients.Statistical analysis was performed by metaanalysis.Four randomized controlled trials met the inclusion criteria.RESULTS: Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80(95%CI: 0.52-1.21, P = 0.29).The overall response rate of S-1 vs capecitabine was 0.94(95%CI: 0.59-1.51, P = 0.93).Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia( O R = 0.9 9, 9 5 % C I : 0.6 5- 1.4 9, P = 0.9 4) a n d thrombocytopenia(OR = 0.72, 95%CI: 0.31-1.67, P = 0.44).The most frequent non-hematologic toxicities included nausea(OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome(OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).CONCLUSION: The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.

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 endoscopic retrograde cholangiography.METHODS:A PE bile duct was characterized by a rigid and relatively narrowed distal CBD with retrograde 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 Center in Chang Gung Memorial Hospital.Patients with characteristic PE bile duct on 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 diameters 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 impacted 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.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting headto-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinicallyasymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.

Squamous cell cancer of the rectum

Squamous cell carcinoma of the rectum is a rare malignancy.It appears to be associated with chronic inflammatory conditions and infections.The clear association seen between Human Papilloma Virus and various squamous cancers has not been firmly established for the squamous cell cancer of the rectum. The presentation is nonspecific and patients tend to present with advanced stage disease.Diagnosis relies on endoscopic examination with biopsy of the lesion.Distinction from squamous cell cancer of the anus can be difficult,but can be facilitated by immunohistochemical staining for cytokeratins.Staging of the cancer with endoscopic ultrasound and computed tomography provides essential information on prognosis and can guide therapy.At present,surgery remains the main therapeutic option;however recent advances have made chemoradiation a valuable therapeutic addition. Squamous cell carcinoma of the rectum is a distinct entity and it is of crucial importance for the practicing Gastroenterologist to be thoroughly familiar with this disease.Compared to adenocarcinoma of the rectum and squamous cell cancer of the anal canal,squamous cell carcinoma of the rectum has different epidemiology, etiology,pathogenesis,and prognosis but,most importantly,requires a different therapeutic approach. This review will examine and summarize the available information regarding this disease from the perspective of the practicing gastroenterologist.

Per oral cholangiopancreatoscopy in pancreatico biliary diseases- Expert consensus statements

AIM: To provide consensus statements on the use of per-oral cholangiopancreatoscopy(POCPS).METHODS: A workgroup of experts in endoscopic retrograde cholangiopancreatography(ERCP), endosonography, and POCPS generated consensus statements summarizing the utility of POCPS in pancreaticobiliary disease. Recommendation grades used validated evidence ratings of publications from an extensive literature review.RESULTS: Six consensus statements were generated:(1) POCPS is now an important additional tool during ERCP;(2) in patients with indeterminate biliary strictures, POCS and POCS-guided targeted biopsy are useful for establishing a definitive diagnosis;(3) POCS and POCS-guided lithotripsy are recommended for treatment of difficult common bile duct stones when standard techniques fail;(4) in patients with main duct intraductal papillary mucinous neoplasms(IPMN) POPS may be used to assess extent of tumor to assist surgicalresection;(5) in difficult pancreatic ductal stones,POPS-guided lithotripsy may be useful in fragmentation and extraction of stones; and(6) additional indications for POCPS include selective guidewire placement,unexplained hemobilia, assessing intraductal biliary ablation therapy, and extracting migrated stents. CONCLUSION: POCPS is important in association with ERCP, particularly for diagnosis of indeterminate biliary strictures and for intra-ductal lithotripsy when other techniques failed, and may be useful for preoperative assessment of extent of main duct IPMN, for extraction of difficult pancreatic stones, and for unusua indications involving selective guidewire placement,assessing unexplained hemobilia or intraductal biliary ablation therapy, and extracting migrated stents.

Endoscopic ultrasonography-guided trucut biopsy for the preoperative diagnosis of peripancreatic castleman's disease: A case report

Castleman's disease (CD) of the pancreas/peripancreas is extremely rare. The recently introduced, endoscopic ultrasonography (EUS)-guided trucut biopsy (TCB) is a useful diagnostic modality for obtaining tissue samples from peripancreatic lesions. However, its role in diagnosing CD remains unknown. We report a case of localized, peripancreatic, hyaline-vascular CD biopsied using EUS. The pathology results were initially interpreted as an extranodal, marginal-zone B-cell lymphoma. However, polymerase chain reaction (PCR) study for the IgH gene rearrangement revealed a polyclonal pattern. We also reviewed the relevant literature. To our knowledge, this is the first illustrated report on EUS-TCB findings of CD with its pathology results of EUS-TCB mimicked a B-cell lymphoma.

Rheumatic manifestations of inflammatory bowel disease

This article reviews the literature concerning rheu-matic manifestations of inflammatory bowel disease (IBD),including common immune-mediated pathways,frequency,clinical course and therapy. Musculoskel-etal complications are frequent and well-recognized manifestations in IBD,and affect up to 33% of pa-tients with IBD. The strong link between the bowel and the osteo-articular system is suggested by many clinical and experimental observations,notably in HLA-B27 transgenic rats. The autoimmune pathogenic mechanisms shared by IBD and spondyloarthropathies include genetic susceptibility to abnormal antigen pre-sentation,aberrant recognition of self,the presence of autoantibodies against specific antigens shared by the colon and other extra-colonic tissues,and increased intestinal permeability. The response against microor-ganisms may have an important role through molecular mimicry and other mechanisms. Rheumatic mani-festations of IBD have been divided into peripheral arthritis,and axial involvement,including sacroiliitis,with or without spondylitis,similar to idiopathic anky-losing spondylitis. Other periarticular features can oc-cur,including enthesopathy,tendonitis,clubbing,peri-ostitis,and granulomatous lesions of joints and bones.Osteoporosis and osteomalacia secondary to IBD and iatrogenic complications can also occur. The manage-ment of the rheumatic manifestations of IBD consists of physical therapy in combination with local injection of corticosteroids and nonsteroidal anti-inflammatory drugs; caution is in order however,because of their possible harmful effects on intestinal integrity,perme-ability,and even on gut inflammation. Sulfasalazine,methotrexate,azathioprine,cyclosporine and lefluno-mide should be used for selected indications. In some cases,tumor necrosis factor-α blocking agents should be considered as first-line therapy.

Role of tissue microenvironment resident adipocytes in colon cancer

Colorectal cancer(CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment(TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors(angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance. Furthermore, adipocytes represent a fuel rich source for increasing energy demand of rapidly proliferating tumour cells. Interestingly, a relationship between obesity and molecular variants in CRC has recently been identified. Whether adipose tissue promotes cancer progression in subsets of molecular phenotypes or whether local tissue adipocytes are involved in inactivation of tumour suppressor genes and/or activation of oncogenes still needs to be explored. This editorial highlights the major findings related to crosstalk between adipocytes and colon cancer cells and how local paracrine interactions may promote cancer progression. Furthermore, we provide future strategies in studying colonic TME which could provide insights in bidirectional cross-talk mechanisms between adipocytes and colonic epithelial cells. This could enable to decipher critical signalling pathways of both early colonic carcinogenesis and cancer progression.

Chronic opioids in gastroparesis: relationship with gastrointestinal symptoms, healthcare utilization and employment

AIM To examine the relationship of chronic scheduled opioid use on symptoms, healthcare utilization and employment in gastroparesis(Gp) patients. Methods Patients referred to our tertiary care academic center from May 2016 to July 2017, with established diagnosis or symptoms suggestive of Gp filled out the Patient Assessment of Upper GI Symptoms, abdominal pain and demographics questionnaires, and underwent gastric emptying and blood tests. They were asked about taking pain medicines and the types, doses, and duration. We used Mann Whitney U test, Analysis of Variance, Student's t test and χ2 tests where appropriate for data analyses.RESULTS Of 223 patients with delayed gastric emptying, 158(70.9%) patients were not taking opioids(Gp NO), 22(9.9%) were taking opioids only as needed, while 43(19.3%) were on chronic(> 1 mo) scheduled opioids(Gp CO), of which 18 were taking opioids forreasons that included gastroparesis and/or stomach pain. Median morphine equivalent use was 60 mg per day. Gp CO reported higher severities of many gastrointestinal symptoms compared to Gp NO including nausea(mean ± SE of mean of 4.09 ± 0.12 vs 3.41 ± 0.12, P = 0.011), retching(2.86 ± 0.25 vs 1.98 ± 0.14, P = 0.003), vomiting(2.93 ± 0.24 vs 2.07 ± 0.15, P = 0.011), early satiety(4.17 ± 0.19 vs 3.57 ± 0.12, P = 0.004), post-prandial fullness(4.14 ± 0.18 vs 3.63 ± 0.11, P = 0.022), loss of appetite(3.64 ± 0.21 vs 3.04 ± 0.13, P = 0.039), upper abdominal pain(3.86 ± 0.20 vs 2.93 ± 0.13, P = 0.001), upper abdominal discomfort(3.74 ± 0.19 vs 3.09 ± 0.13, P = 0.031), heartburn during day(2.55 ± 0.27 vs 1.89 ± 0.13, P = 0.032), heartburn on lying down(2.76 ± 0.28 vs 1.94 ± 0.14, P = 0.008), chest discomfort during day(2.42 ± 0.20 vs 1.83 ± 0.12, P = 0.018), chest discomfort at night(2.40 ± 0.23 vs 1.61 ± 0.13, P = 0.003), regurgitation/reflux during day(2.77 ± 0.25 vs 2.18 ± 0.13, P = 0.040) and bitter/acid/sour taste in the mouth(2.79 ± 0.27 vs 2.11 ± 0.14, P = 0.028). Gp CO had a longer duration of nausea per day(median of 7 h vs 4 h for Gp NO, P = 0.037), and a higher number of vomiting episodes per day(median of 3 vs 2 for Gp NO, P = 0.002). Their abdominal pain more frequently woke them up at night(78.1% vs 57.3%, P = 0.031). They had a lower employment rate(33.3% vs 54.2%, P = 0.016) and amongst those who were employed less number of working hours per week(median of 23 vs 40, P = 0.005). They reported higher number of hospitalizations in the last 1 year(mean ± SE of mean of 2.90 ± 0.77 vs 1.26 ± 0.23, P = 0.047). CONCLUSION Gp CO had a higher severity of many gastrointestinal symptoms, compared to Gp NO. Hospitalization rates were more than 2-fold higher in Gp CO than Gp NO.Gp CO also had lower employment rate and working hours, when compared to Gp NO.

Doctor communication quality and Friends' attitudes influence complementary medicine use in inflammatory bowel disease

AIM: To examine the frequency of regular complementary and alternative therapy(CAM) use in three Australian cohorts of contrasting care setting and geography, and identify independent attitudinal and psychological predictors of CAM use across all cohorts. METHODS: A cross sectional questionnaire was administered to inflammatory bowel disease(IBD) patients in 3 separate cohorts which differed by geographical region and care setting. Demographics and frequency of regular CAM use were assessed, along with attitudes towards IBD medication and psychological parameters such as anxiety, depression, personality traits and quality of life(QOL), and compared across cohorts. Independent attitudinal and psychological predictors of CAM use were determined using binary logistic regression analysis. RESULTS: In 473 respondents(mean age 50.3 years, 60.2% female) regular CAM use was reported by45.4%, and did not vary between cohorts. Only 54.1%of users disclosed CAM use to their doctor. Independent predictors of CAM use which confirm those reported previously were: covert conventional medication dose reduction(P < 0.001), seeking psychological treatment(P < 0.001), adverse effects of conventional medication(P = 0.043), and higher QOL(P < 0.001).Newly identified predictors were CAM use by family or friends(P < 0.001), dissatisfaction with patient-doctor communication(P < 0.001), and lower depression scores(P < 0.001). CONCLUSION: In addition to previously identified predictors of CAM use, these data show that physician attention to communication and the patient-doctor relationship is important as these factors influence CAM use. Patient reluctance to discuss CAM with physicians may promote greater reliance on social contacts to influence CAM decisions.

Hepatitis B virus reactivation with a rituximab-containing regimen

Rituximab is currently used not only in the treatment of B-cell lymphoma but also for various other diseases, including autoimmune diseases, post-transplant graft vs host disease, and rejection following kidney transplants. Due to rituximab's widespread use, great progress has been made regarding research into complications that arise from its use, one of the most serious being the reactivation of hepatitis B virus(HBV), and efforts continue to establish guidelines for preventive treatment against this occurrence. This report discusses preventive measures against rituximab-induced HBV reactivation and future objectives.

Gene therapy in pancreatic cancer

Pancreatic cancer(PC) is a highly lethal disease and notoriously difficult to treat. Only a small proportion of PC patients are eligible for surgical resection, whilst conventional chemoradiotherapy only has a modest effect with substantial toxicity. Gene therapy has become a new widely investigated therapeutic approach for PC.This article reviews the basic rationale, gene delivery methods, therapeutic targets and developments of laboratory research and clinical trials in gene therapy of PC by searching the literature published in English using the PubMed database and analyzing clinical trials registered on the Gene Therapy Clinical Trials Worldwide website(http://www. wiley.co.uk/genmed/ clinical). Viral vectors are main gene delivery tools in gene therapy of cancer, and especially, oncolytic virus shows brighter prospect due to its tumor-targeting property.Efficient therapeutic targets for gene therapy include tumor suppressor gene p53, mutant oncogene K-ras,anti-angiogenesis gene VEGFR, suicide gene HSK-TK,cytosine deaminase and cytochrome p450, multiple cytokine genes and so on. Combining different targets or combination strategies with traditional chemoradiother-apy may be a more effective approach to improve the efficacy of cancer gene therapy. Cancer gene therapy is not yet applied in clinical practice, but basic and clinical studies have demonstrated its safety and clinical benefits. Gene therapy will be a new and promising field for the treatment of PC.

Serum bile acid profiling reflects enterohepatic detoxification state and intestinal barrier function in inlammatory bowel disease

AIM:To determine free and conjugated serum bile acid (BA) levels in in? ammatory bowel disease (IBD) subgroups with defi ned clinical manifestations.METHODS: Comprehensive serum BA profiling was performed in 358 IBD patients and 310 healthy controls by liquid chromatography coupled to electrospray ionization tandem mass spectrometry.RESULTS: Serum levels of hyodeoxycholic acid, the CYP3A4-mediated detoxification product of the secondary BA lithocholic acid (LCA), was increased significantly in Crohn's disease (CD) and ulcerative colitis (UC), while most other serum BA species were decreased significantly. Total BA, total BA conjugate, and total BA glycoconjugate levels were decreased only in CD, whereas total unconjugated BA levels were decreased only in UC. In UC patients with hepatobiliary manifestations, the conjugated primary BAs glycocholic acid, taurocholic acid, and glycochenodeoxycholic acid were as significantly increased as the secondary BAs LCA, ursodeoxycholic acid, and tauroursodeoxycholic acid compared to UC patients without hepatobiliary manifestations. Finally, we found that in ileocecal resected CD patients, the unconjugated primary BAs, cholic acid and chenode-oxycholic acid, were increased significantly compared to controls and patients without surgical interventions.CONCLUSION: Serum BA profiling in IBD patients that indicates impaired intestinal barrier function and increased detoxification is suitable for advanced diagnostic characterization and differentiation of IBD subgroups with defined clinical manifestations.

Olfactomedin-4 in digestive diseases: A mini-review

Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.