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Serum immune-activation potency and response to anti-TNF-α therapy in Crohn's disease

World Journal of gastroenterology 2010年第46期16卷 5845-5851页

作者： Hanne Rintamki Taina Sipponen Harri M Salo Outi Vaarala Kaija-Leena Kolho division of gastroenterology Hospital for Children and Adolescents and Helsinki University Central HospitalUniversity of Helsinki Department of Medicine Division of GastroenterologyHelsinki University Central HospitalUniversity of Helsinki Immune Response Unit Department of Vaccination and Immune ProtectionNational Institute for Health and Welfare

AIM:To study whether immune-activation stage in serum of adult Crohn's disease (CD) patients correlates with disease activity and with treatment response to antitumor necrosis factor-α (TNF-α) ***:Serum samples were obtained from 15 adult CD patients introduced to anti-TNF-α *** individual stage of immune activation was studied applying our new in vitro assay,in which target cells (donor derived peripheral blood mononuclear cells) were cultured with patient serum and the T-cell activation induced by the patient serum was studied using a panel of markers for effector [interferon γ (IFNγ),interleukin (IL)-5] and regulatory T-cells [forkhead transcription factor 3 (FOXP3) and glucocorticoid-induced tumour necrosis factor receptor (GITR)].The endoscopic disease activity was assessed with the Crohn's disease endoscopic index of severity (CDEIS) before and 3 mo after therapy with an anti-TNF-α ***:Low induction of FOXP3 and GITR in target cells cultured in the presence of patient serum was associated with high disease activity *** assessed before therapy (r=-0.621,P=0.013 and r=-0.625,P=0.013,respectively).FOXP3 expression correlated inversely with pre-treatment erythrocyte sedimentation rate (r=-0.548,P=0.034).Low serum induced FOXP3 (r=-0.600,P=0.018) and GITR (r=-0.589,P=0.021) expression and low IFNγ secretion from target cells (r =-0.538,P=0.039) associated with treatment response detected as a decrease in ***:The immune-activation potency in the patient serum prior to anti-TNF-α therapy reflected intestinal inflammation and the therapeutic response.

关键词： Crohn’s disease endoscopic index of severity Forkhead transcription factor 3 Glucocorticoid-induced tumour necrosis factor receptor Infliximab Inflammatory bowel disease

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Endoscopic ultrasound-fine needle injection for oncological therapy

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World Journal of Gastrointestinal Oncology 2015年第12期7卷 466-472页

作者： Jeremy Kaplan Amaara Khalid Natalie Cosgrove Ayesha Soomro Syed Mohsin Mazhar Ali A Siddiqui division of gastroenterology and Hepatology Department of Internal Medicine Thomas Jefferson University Hospital

The minimal invasiveness and precision of endoscopicultrasound(EUS) has lead to both its widespread use as a diagnostic and staging modality for gastrointestinal and pancreaticobiliary malignancies, and to its expand-ing role as a therapeutic modality. EUS-guided celiac plexus neurolysis is now a well-accepted modality for palliation of pain in patients with pancreatic cancer. EUS-guided ablation, brachytherapy, fiducial marker placement, and antitumor agent injection have been described as methods of performing minimally invasive oncological therapy. EUS-fine needle injection may be performed as adjunctive, alternative, or palliative treatment. This review summarizes the studies to date that have described these methods. A literature search using the Pub Med/MEDLINE databases was performed. While most published studies to date are limited with disappointing outcomes, the concept of a role of EUS in oncological therapy seems promising.

关键词： Endoscopic ultrasound-fine needle injection Endosc

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KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study

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Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 62-66页

作者： Jung Hyun Jo Huapyong Kang Hee Seung Lee Moon Jae Chung Jeong Youp Park Seungmin Bang Seung Woo Park Si Young Song division of gastroenterology Department of Internal Medicine Severance Hospital Yonsei University College of Medicine

Background: Sodium meta-arsenite(NaAsO_2, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer(BTC) resistant to gemcitabinebased chemotherapy. Methods: Forty-four patients(21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status(PS) 0–2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001(7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT. Results: After an average of 1.5 months of treatment(range: 0.5–10.0), 3 patients(6.8%) obtained progression-free status, 23 patients(52.3%) had disease progression, and 18 patients(40.9%) dropped out before evaluation. One patient(2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients(47.6%). Nine patients(20.5%) experienced grade-3 adverse events(AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation(11/44, 25%) and anemia(10/44, 22.7%). KML001 was discontinued in six patients(13.6%) due to AEs, including liver toxicity( n = 3), QTc prolongation( n = 2), and abdominal pain( n = 1). Conclusions: KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.

关键词： Biliary tract neoplasms Cholangiocarcinoma Gallbladder neoplasms KML001 Sodium meta-arsenite

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Hepatitis C virus therapy with peg-interferon and ribavirin in Myanmar: A resource-constrained country

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World Journal of gastroenterology 2016年第43期22卷 9613-9622页

作者： Naomi Khaing Than Hlaing Debolina Banerjee Robert Mitrani Soe Htet Arker Kyaw San Win Nyan Lin Tun Zaw Thant Khin Maung Win K Rajender Reddy Department of Hepatology Mandalay General Hospital division of gastroenterology and Hepatology University of Pennsylvania

AIM To investigate peg-interferon(peg-IFN) and ribavirin(RBV) therapy in Myanmar and to predict sustained virologic response(SVR).METHODS This single-center, open-label, study was conducted in Myanmar between 2009 and 2014. A total of 288 patients infected with HCV genotypes 1, 2, 3 and 6 were treated with peg-IFN alpha-2a(180 μg/wk) or alpha-2b(50 to 100 μg as a weight-based dose) and RBV as a weight-based dose(15 mg/kg/d). Treatment duration was 48 wk for genotypes 1 and 6, 24 wk for genotype 2, and 24 or 48 wk for genotype 3 based on rapid virologic response(RVR). Those co-infected with hepatitis B received 48 wk of *** Overall, SVR was achieved for 82% of patients and the therapy was well tolerated. All patients achieved SVR at equivalent rates regardless of HCV genotype(P = 0.314). Low fibrosis scores(P 96% positive predictive value for achieving SVR. Treatment duration did not significantly impact the likelihood of achieving SVR for patients infected with genotype 3 HCV(P = 0.371). The most common adverse events were fatigue(71%) and poor appetite(60%). Among patients with genotype 3 HCV, more patients in the 48-wk treatment group required erythropoietin than in the 24-wk treatment group(61.1% vs 49.2%).CONCLUSION SVR rates were high with peg-IFN and RBV therapy in Myanmar. Fibrosis scores, baseline albumin, HCV RNA levels and RVR independently predicted SVR.

关键词： Hepatitis C virus Pegylated-interferon Ribavirin Sustained virologic response Rapid virologic response

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Bedside index for severity in acute pancreatitis:comparison with other scoring systems in predicting severity and organ failure

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Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 645-650页

作者： Ji Young Park Tae Joo Jeon Tae Hwan Ha Jin Tae Hwang Dong Hyun Sinn Tae-Hoon Oh Won Chang Shin Won-Choong division of gastroenterology Department of Internal MedicineInje University Sanggye Paik Hospital

BACKGROUND:The early identification of severe acute pancreatitis is important for the management and for improving *** bedside index for severity in acute pancreatitis(BISAP)has been considered as an accurate method for risk stratification in patients with acute *** study aimed to evaluate the comparative usefulness of the ***:We retrospectively analyzed 303 patients with acute pancreatitis diagnosed at our hospital from March 2007to December ***,APACHE-II,Ranson criteria,and CT severity index(CTSI)of all patients were *** stratified the number of patiants with severe pancreatitis,pancreatic necrosis,and organ failure as well as the number of deaths by BISAP *** used the area under the receiveroperating curve(AUC)to compare BISAP with other scoring systems,C-reactive protein(CRP),hematocrit,and body mass index(BMI)with regard to prediction of severe acute pancreatitis,necrosis,organ failure,and ***:Of the 303 patiants,31(10.2%)were classified as having severe acute *** failure occurred in 23(7.6%)patients,pancreatic necrosis in 40(13.2%),and death in6(2.0%).A BISAP score of 2 was a statistically significant cutoff value for the diagnosis of severe acute pancreatitis,organ failure,and *** for BISAP predicting severe pancreatitis and death were 0.80 and 0.86,respectively,which were similar to those for APACHE-II(0.80,0.87)and Ranson criteria(0.74,0.74)and greater than AUCs for CTSI(0.67,0.42).The AUC for organ failure predicted by BISAP,APACHE-II,Ranson criteria,and CTSI was 0.93,0.95,0.84 and 0.57,*** for BISAP predicting severity,organ failure,and death were greater than those for CRP(0.69,0.80,0.72),hematocrit(0.45,0.35,0.14),and BMI(0.41,0.47,0.17).CONCLUSION:The BISAP predicts severity,death,and especially organ failure in acute pancreatitis as well as APACHE-II does and better than Ranson criteria,CTSI,CRP,hematocrit,and BMI.

关键词： acute pancreatitis scoring system pancreatic necrosis organ failure

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Second-line rescue treatment of Helicobacter pylori infection: Where are we now?

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World Journal of gastroenterology 2018年第40期24卷 4548-4553页

作者： Te-Fu Lin Ping-I Hsu division of gastroenterology and Hepatology Department of Internal Medicine Kaohsiung Veterans General Hospital

At present, the best rescue therapy for Helicobacter pylori(H. pylori) infection following failure of firstline eradication remains unclear. The Maastricht Ⅴ/Florence Consensus Report recommends bismuth quadruple therapy, or fluoroquinolone-amoxicillin triple/quadruple therapy as the second-line therapy for H. pylori infection. Meta-analyses have shown that bismuth quadruple therapy and levofloxacin-amoxicillin triple therapy have comparable eradication rates, while the former has more adverse effects than the latter. There are no significant differences between the eradication rates of levofloxacin-amoxicillin triple and quadruple therapies. However, the eradication rates of both levofloxacin-containing treatments are suboptimal. An important caveat of levofloxacin-amoxicillin triple or quadruple therapy is poor eradication efficacy in the presence of fluoroquinolone resistance. High-dose dual therapy is an emerging second-line therapy and has an eradication efficacy comparable with levofloxacinamoxicillin triple therapy. Recently, a 10-d tetracyclinelevofloxacin(TL) quadruple therapy comprised of a proton pump inhibitor, bismuth, tetracycline and levofloxacin has been developed, which achieves a markedly higher eradication rate compared with levofloxacin-amoxicillin triple therapy(98% vs 69%) in patients with failure of standard triple, bismuth quadruple or non-bismuth quadruple therapy. The present article reviews current second-line anti-H. pylori regimens and treatment algorisms. In conclusion, bismuth quadruple therapy, levofloxacin-amoxicillin triple/quadruple therapy, high-dose dual therapy and TL quadruple therapy can be used as second-line treatment for H. pylori infection. Current evidence suggests that 10-d TL quadruple therapy is a simple and effective regimen, and has the potential to become a universal rescue treatment following eradication failure by all firstline eradication regimens for H. pylori infection.

关键词： Helicobacter pylori Rescue treatment Levofloxacin-amoxicillin triple therapy Bismuth quadruple therapy Tetracycline-levofloxacin quadruple therapy High-dose dual therapy

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Effect of endogenous hypergastrinemia on gallbladder volume and ejection fraction in patients with autoimmune gastritis

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Hepatobiliary & Pancreatic Diseases International 2012年第5期11卷 527-531页

作者： Mustafa Yakut Onur Keskin Irfan Soykan division of gastroenterology Ibni Sina HospitalAnkara University Faculty of Medicine

BACKGROUND: Gastrin has a cholecystokinetic action on gallbladder motility, and cholecystokinin and gastrin act directly on the smooth muscle of the gallbladder. The aim of this study was to investigate the effect of endogenous hypergastrinemia on gallbladder motility in patients with autoimmune gastritis. METHODS: Forty-one patients (29 females, 12 males; mean age, 46 years) with autoimmune gastritis and 29 healthy subjects (17 females, 12 males; mean age, 44.8 years) were enrolled in the study. Fasting and postprandial gallbladder volumes were measured ultrasonographically with the ellipsoid technique and the ejection fraction of the gallbladder was calculated from fasting and postprandial volumes. All subjects were investigated after 12 hours of fasting and 30 minutes after a standard test meal. RESULTS: The gallbladder ejection fraction (%) of the patients with autoimmune gastritis was lower than that of the control group (46.06±18.28% vs 55.03±14.67%, P=0.032). There was no difference between patients with autoimmune gastritis and the control group in terms of the mean fasting gallbladder volume (30.38±12.85 vs 29.27±9.91 cm 3 , P=0.189) and the mean postprandial gallbladder volume (15.67±8.32 vs 13.44±7.69 cm 3 , P=0.258). Logistic regression analysis of baseline parameters revealed that 'abdominal bloating' was a risk factor for the low gallbladder ejection fraction in autoimmune gastritis patients (P=0.045, F=4.40). In addition, logistic regression analysis of baseline parameters revealed that smoking (n=5, P=0.025, F=5.44) is a predictor of low gallbladder ejection fraction in patients with autoimmune ***: Patients with endogenous hypergastrinemia have a low gallbladder ejection fraction compared with healthy controls. This study shows that at least part of upper gastrointestinal symptoms observed in this patient population may be due to altered gallbladder motility.

关键词： gallbladder motility autoimmune gastritis hypergastrinemia

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Diagnostic delay in inflammatory bowel disease increases the risk of intestinal surgery

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World Journal of gastroenterology 2017年第35期23卷 6474-6481页

作者： Dong-won Lee Ja Seol Koo Jung Wan Choe Sang Jun Suh Seung Young Kim Jong Jin Hyun Sung Woo Jung Young Kul Jung Hyung Joon Yim Sang Woo Lee division of gastroenterology and Hepatology Department of Internal MedicineKorea University Ansan Hospital

AIM To investigate the factors affecting diagnostic delay and outcomes of diagnostic delay in inflammatory bowel disease(IBD) METHODS We retrospectively studied 165 patients with Crohn's disease(CD) and 130 patients with ulcerative colitis(UC) who were diagnosed and had follow up durations > 6 mo at Korea University Ansan hospital from January 2000 to December 2015. A diagnostic delay was defined as the time interval between the first symptom onset and IBD diagnosis in which the 76^(th) to 100^(th) percentiles of patients were *** The median diagnostic time interval was 6.2 and 2.4 mo in the patients with CD and UC, respectively. Among the initial symptoms, perianal discomfort before diagnosis(OR = 10.2, 95%CI: 1.93-54.3, P = 0.006) was associated with diagnostic delays in patients with CD; however, no clinical factor was associated with diagnostic delays in patients with UC. Diagnostic delays, stricturing type, and penetrating type were associated with increased intestinal surgery risks in CD(OR = 2.54, 95%CI: 1.06-6.09; OR = 4.44, 95%CI: 1.67-11.8; OR = 3.79, 95%CI: 1.14-12.6, respectively). In UC, a diagnostic delay was the only factor associated increased intestinal surgery risks(OR = 6.81, 95%CI: 1.12-41.4).CONCLUSION A diagnostic delay was associated with poor outcomes, such as increased intestinal surgery risks in patients with CD and UC.

关键词： Diagnostic delay Intestinal surgery Inflammatory bowel disease Crohn’s disease Ulcerative colitis

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Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

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World Journal of gastroenterology 2017年第13期23卷 2414-2423页

作者： Hiroki Sato Nao Nakajima Kazuya Takahashi Go Hasegawa Ken-ichi Mizuno Satoru Hashimoto Satoshi Ikarashi Kazunao Hayashi Yutaka Honda Junji Yokoyama Yuichi Sato Shuji Terai division of gastroenterology and Hepatology Niigata University Medical and Dental Hospital division of gastroenterology and Hepatology Saiseikai Niigata Daini Hospital division of Cellular and Molecular Pathology Department of Cellular FunctionNiigata University Graduate School of Medical and Dental Sciences

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue *** In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo *** Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.

关键词： Eosinophilic esophagitis Eosinophilic esophageal myositis Peroral endoscopic myotomy Jackhammer esophagus Achalasia Peroral esophageal muscle biopsy

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hospital readmissions in decompensated cirrhotics: Factors pointing toward a prevention strategy

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World Journal of gastroenterology 2017年第37期23卷 6868-6876页

作者： Siamak M Seraj Emily J Campbell Sarah K Argyropoulos Kara Wegermann Raymond T Chung James M Richter Massachusetts General hospital Division of Gastroenterology Duke University hospital Department of Medicine Harvard Medical School

AIM To reduce readmissions and improve patient outcomes in cirrhotic patients through better understanding of readmission *** We performed a single-center retrospective study of patients admitted with decompensated cirrhosis from January 1, 2011 to December 31, 2013(n = 222). Primary outcomes were time to first readmission and 30-d readmission rate due to complications of cirrhosis. Clinical and demographic data were collected to help describe predictors of readmission, along with care coordination measures such as post-discharge status and outpatient follow-up. Univariate and multivariateanalyses were performed to describe variables associated with *** One hundred thirty-two patients(59.4%) were readmitted at least once during the study period. Median time to first and second readmissions were 54 and 93 d, respectively. Thirty and 90-d readmission rates were 20.7 and 30.1 percent, respectively. Predictors of 30-d readmission included education level, hepatic encephalopathy at index, ALT more than upper normal limit and Medicare coverage. There were no statistically significant differences in readmission rates when stratified by discharge disposition, outpatient follow-up provider or time to first outpatient *** Readmissions are challenging aspect of care for cirrhotic patients and risk continues beyond 30 d. More initiatives are needed to develop enhanced, longitudinal post-discharge systems.

关键词： Chronic disease Re-hospitalizations Liver disease Readmissions Cirrhosis Chronic care

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