Cellular and Molecular Mechanisms of Intestinal Fibrosis

Intestinal fibrosis associated stricture is a common complication of inflammatory bowel disease usually requiring endoscopic or surgical intervention. Effective anti-fibrotic agents aiming to control or reverse intestinal fibrosis are still unavailable. Thus, clarifying the mechanism underpinning intestinal fibrosis is imperative. Fibrosis is characterized by an excessive accumulation of extracellular matrix (ECM) proteins at the injured sites. Multiple cellular types are implicated in fibrosis development. Among these cells, mesenchymal cells are major compartments that are activated and then enhance the production of ECM. Additionally, immune cells contribute to the persistent activation of mesenchymal cells and perpetuation of inflammation. Molecules are messengers of crosstalk between these cellular compartments. Although inflammation is necessary for fibrosis development, purely controlling intestinal inflammation cannot halt the development of fibrosis, suggesting that chronic inflammation is not the unique contributor to fibrogenesis. Several inflammation-independent mechanisms including gut microbiota, creeping fat, ECM interaction, and metabolic reprogramming are involved in the pathogenesis of fibrosis. In the past decades, substantial progress has been made in elucidating the cellular and molecular mechanisms of intestinal fibrosis. Here, we summarized new discoveries and advances of cellular components and major molecular mediators that are associated with intestinal fibrosis, aiming to provide a basis for exploring effective anti-fibrotic therapies in this field.

A multicenter survey on the psychological status and quality of life of patients with inflammatory bowel disease in China / 中华消化杂志

Objective:To investigate the psychology status and quality of life in patients with inflammatory bowel disease(IBD) in China, and to analyze the influencing factors.Methods:From September 2021 to May 2022, 42 hospitals in 22 provinces(autonomous regions and municipalities directly under the central government) in China, the clinical data of 2 478 IBD patients were collected, which included age, gender, weight, first visit or not, disease activity, disease course, main clinical manifestations(diarrhea, abdominal pain, hematochezia, extraintestinal manifestations), complications, treatment medication(5-aminosalicylic acid, glucocorticoids, immunosuppressive agents, and biological agents), and whether to have surgery. Anxiety, depression, sleep quality and quality of life of IBD patients were evaluated by generalized anxiety disorder-7 items, patient health questionnaire-9 items, Pittsburgh sleep quality index and inflammatory bowel disease questionnaire, and the related influencing factors were analyzed. Univariate analysis and multiple linear regression analysis were used for statistical analysis.Results:The average age of 2 478 IBD patients was 37.96 years old, and male counted for 62.43%(1 547/2 478). There were 61.82%(1 532/2 478) of the IBD patients in the active stage of disease, mostly mild or moderate(588 and 734 cases). There were 60.61%(1 502/2 478) of the IBD patients with different degrees of anxiety, 58.35%(1 446/2 478) of the IBD patients with different degrees of depression, and 48.87%(1 211/2 478) of the IBD patients had different degrees of sleep problems. The results of multiple linear regression analysis indicated that female, higher level of disease activity and longer disease course were independent risk factors of anxiety, depression and sleep quality in the IBD patients(unstandardized regression coefficient(95% confidence interval) 1.08(0.65 to 1.50), 0.45(0.23 to 0.68), 0.19(0.02 to 0.36), 0.83(0.33 to 1.32), 0.62(0.36 to 0.88), 0.28(0.08 to 0.47), 0.47(0.16 to 0.77), 0.39(0.23 to 0.55), 0.14(0.02 to 0.26); P<0.001, <0.001, =0.025 , =0.001, <0.001, =0.005, =0.003, <0.001, =0.027). The usage of biological agents was an independent protective factor of anxiety(unstandardized regression coefficient(95% confidence interval) -0.67(-1.17 to -0.17), P=0.008), and older age was an independent risk factor of sleep quality(unstandardized regression coefficient(95% confidence interval) 0.35(0.09 to 0.61), P=0.008). Higher level of disease activity, symptoms of diarrhea, abdominal pain, presence of extraintestinal manifestations, usage of 5-aminosalicylic acid and glucocorticoid, and with surgical treatment were independent risk factors of quality of life(unstandardized regression coefficient(95% confidence interval) -11.00(-12.24 to -9.76), -2.90(-5.26 to -0.55), -3.93(-6.25 to -1.61), -5.79(-9.87 to -1.71), -4.78(-7.79 to -1.76), -7.71(-11.07 to -4.35), -4.37(-8.00 to -0.73); P<0.001, =0.016, =0.001, =0.005 , =0.002, <0.001, =0.019), while the usage of biological agents was an independent protective factor of quality of life (unstandardized regression coefficient(95% confidence interval) 4.72(1.97 to 7.48), P=0.001). Conclusion:IBD patients generally have different degrees of anxiety, depression and sleep problems, which affect the quality of life of patients. Gender, disease activity and disease course are the influencing factors of mental disorders in IBD patients.

Chinese consensus on diagnosis and treatment of intestinal Beh?et′s disease / 中华消化杂志

Beh?et′s syndrome is a kind of chronic systemic vasculitis with involvement of multiple organs. Intestinal involvement of Beh?et′s syndrome is presently named as intestinal Beh?et′s syndrome. Recently, there is considering another kind of disease type with only typical intestinal ulcers. Since it is difficult to differentiate intestinal Beh?et′s syndrome from Crohn′s disease, intestinal tuberculosis, intestinal lymphoma, and intestinal manifestations of many other autoimmune diseases, and there is limited evidence for the therapy of intestinal Beh?et′s syndrome, proposing diagnosis and treatment recommendations for intestinal Beh?et′s syndrome through evidence-based judgment will be of great significance for clinical practice.

Risk Factors Associated with Impaired Ovarian Reserve in Young Women of Reproductive Age with Crohn’s Disease

Background/Aims@#Crohn’s disease (CD) primarily affects young female adults of reproductive age. Few studies have been conducted on this population’s ovarian reserve status. The aim of study was to investigate potential risk factors associated with low ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) in women of reproductive age with CD. @*Methods@#This was a case-control study. Cases included 87 patients with established CD, and healthy controls were matched by age, height and weight in a 1:1 ratio. Serum AMH levels were measured by enzyme-linked immunosorbent assay. @*Results@#The average serum AMH level was significantly lower in CD patients than in control group (2.47±2.08 ng/mL vs. 3.87±1.96 ng/mL, respectively, P<0.001). Serum AMH levels were comparable between CD patients and control group under 25 years of age (4.41±1.52 ng/mL vs. 3.49±2.10 ng/mL, P=0.06), however, serum AMH levels were significantly lower in CD patients over 25 years of age compared to control group (P<0.05). Multivariable analysis showed that an age greater than 25 (odds ratio [OR], 10.03; 95% confidence interval [CI], 1.90–52.93, P=0.007), active disease state (OR, 27.99; 95% CI, 6.13–127.95, P<0.001) and thalidomide use (OR, 15.66; 95% CI, 2.22–110.65, P=0.006) were independent risk factors associated with low ovarian reserve (serum AMH levels <2 ng/mL) in CD patients. @*Conclusions@#Ovarian reserve is impaired in young women of reproductive age with CD. Age over 25 and an active disease state were both independently associated with low ovarian reserve. Thalidomide use could result in impaired ovarian reserve.

2019 Seoul Consensus on Esophageal Achalasia Guidelines

Esophageal achalasia is a primary motility disorder characterized by insufficient lower esophageal sphincter relaxation and loss of esophageal peristalsis. Achalasia is a chronic disease that causes progressive irreversible loss of esophageal motor function. The recent development of high-resolution manometry has facilitated the diagnosis of achalasia, and determining the achalasia subtypes based on high-resolution manometry can be important when deciding on treatment methods. Peroral endoscopic myotomy is less invasive than surgery with comparable efficacy. The present guidelines (the “2019 Seoul Consensus on Esophageal Achalasia Guidelines”) were developed based on evidence-based medicine; the Asian Neurogastroenterology and Motility Association and Korean Society of Neurogastroenterology and Motility served as the operating and development committees, respectively. The development of the guidelines began in June 2018, and a draft consensus based on the Delphi process was achieved in April 2019. The guidelines consist of 18 recommendations: 2 pertaining to the definition and epidemiology of achalasia, 6 pertaining to diagnoses, and 10 pertaining to treatments. The endoscopic treatment section is based on the latest evidence from meta-analyses. Clinicians (including gastroenterologists, upper gastrointestinal tract surgeons, general physicians, nurses, and other hospital workers) and patients could use these guidelines to make an informed decision on the management of achalasia.

Clinical efficacy of modified peroral endoscopic myotomy in the treatment of 51 cases of achalasia / 中华消化杂志

Objective:To evaluate the effects of modified peroral endoscopic myotomy (POEM) on esophageal dynamics and clinical efficacy in achalasia (AC) patients.Methods:From January 2013 to December 2014, 51 patients diagnosed with AC and received modified POEM at The First Affiliated Hospital of Sun Yat-sen University were retrospectively enrolled. AC patients were classified as type Ⅰ, type Ⅱ and type Ⅲ according to Chicago classification. The changes of esophageal dynamics before and after the modified POEM were compared by high resolution manometry (HRM). The reflux after the operation was evaluated by 24-hour esophageal impedance-pH monitoring. The clinical symptoms and the quality of life of AC patients were assessed by impaction dysphagia questionnaire (IDQ), Eckardt scale and short-form 36 item health survey (SF-36). Paired t test, independent sample t test, Wilcoxon rank sum test and Pearson correlation analysis were used for statistical analysis. Results:At three months and one year after operation, lower esophageal sphincter pressure (LESP) and integrated relaxation pressure (IRP) were all lower than those before operation ((23.89±12.68) and (23.44±12.56) mmHg (1 mmHg=0.133 kPa) vs. (39.29±16.14) mmHg; (16.13±9.43) and (15.37±8.36) mmHg vs. (30.57±11.31) mmHg), and the differences were statistically significant ( t=7.520, 7.866, 7.641 and 8.909, all P<0.05). There were no statistically significant differences in LESP and IRP during the same period between patients with type Ⅰ AC and type Ⅱ AC (all P>0.05). The LESP of patients with partial esophageal peristalsis function recovered one year after operation was lower than that of patients with unrecovered esophageal peristalsis function ((15.38±4.54) mmHg vs. (25.65±13.19) mmHg), and the difference was statistically significant ( t=0.039, P<0.05). The proportions of pathologic acid reflux of AC patients at three months and one year after operation were 7.8%(4/51) and 2.0%(1/51), respectively. The IDQ and Eckardt scores of patients with AC at three months and one year after operation were both lower than those before operation (4 points, 0 points to 10 points and 4 points, 0 points to 11 points vs. 23 points, 18 points to 30 points; 2 points, 1 points to 3 points and 1 points, 0 points to 1 points vs. 5 points, 4 points to 5 points), and the differences were statistically significant ( Z=-6.036, -6.104, -5.971 and -6.209, all P<0.01). According to Eckardt score, the proportions of clinical remission at three months and one year after operation were higher than that before operation (98.0%, 50/51 and 100.0%, 51/51 vs. 19.6%, 10/51), and the differences were statistically significant ( χ2=64.76 and 68.56, both P<0.05). The SF-36 general health and social function scores at three months and one year after operation were both higher than those before operation (0.55 points, 0.45 points to 0.70 points and 0.55 points, 0.45 points to 0.70 points vs. 0.45 points, 0.30 points to 0.55 points; 0.88 points, 0.75 points to 1.00 points and 0.88 points, 0.75 points to 1.12 points vs. 0.75 points, 0.75 points to 1.00 points); and the differences were statistically significant ( Z=-4.439, -4.225, -2.123 and -2.320, all P<0.05); and the health change scores were lower than those before operation (3.00 points, 2.00 points to 3.00 points and 2.00 points, 1.00 points to 3.00 points vs. 4.00 points, 3.00 points to 4.00 points), and the differences were statistically significant ( Z=-4.827 and -4.841, both P<0.05). Before and after modified POEM, the changes of LESP were positively correlated with the changes of IRP ( r=0.624 and 0.592, both P<0.01). Conclusion:Modified POEM can significantly improve the symptoms and LES relaxation function of AC patients, with a low incidence of post-operative reflux.

Thalidomide in refractory Crohn′s disease: long-term efficacy and safety / 中华内科杂志

Objective:To analyze the long-term efficacy and safety of thalidomide on refractory Crohn′s disease (CD).Methods:A total of 79 patients with refractory CD in the First Affiliated Hospital of Sun Yat-sen University treated with thalidomide were enrolled in this retrospective study from September 2005 to July 2018. Clinical effects and adverse drug reactions were recorded and assessed.Results:In this cohort,69 patients were treated with thalidomide for ≥6 months. Sixty-eight patients among the 69 patients achieved complete clinical remission and were followed up for a median 33.5 months (range, 7-110 months). Seventeen cases relapsed during follow-up. The cumulative probabilities of remaining in remission at 12, 24, 60 months were 88.6% (95% CI 80.6%-96.6%), 80.7% (95% CI 70.3%-91.1%), 53.7% (95% CI 32.1%-75.3%) respectively. Disease activity was the only variable associated with relapse risk, with a hazard ratio ( HR) of 3.559 for Crohn′s disease activity index (CDAI) ≥220(95% CI 1.213-10.449, P<0.05). Adverse reactions were recorded in 42 (53.2%) patients including12 (15.2%) leading to discontinuation of thalidomide. No serious side effects were observed in all subjects. Conclusions:This study suggests a long-term benefit of maintenance treatment with thalidomide in refractory CD.Moderate to severe patients have an increased risk of relapse. The high incidence of drug adverse reactions may restrain the clinical application of thalidomide.

Second Asian Consensus on Irritable Bowel Syndrome

BACKGROUND/AIMS: There has been major progress in our understanding of the irritable bowel syndrome (IBS), and novel treatment classes have emerged. The Rome IV guidelines were published in 2016 and together with the growing body of Asian data on IBS, we felt it is timely to update the Asian IBS Consensus. METHODS: Key opinion leaders from Asian countries were organized into 4 teams to review 4 themes: symptoms and epidemiology, pathophysiology, diagnosis and investigations, and lifestyle modifications and treatments. The consensus development process was carried out by using a modified Delphi method. RESULTS: Thirty-seven statements were developed. Asian data substantiate the current global viewpoint that IBS is a disorder of gut-brain interaction. Socio-cultural and environmental factors in Asia appear to influence the greater overlap between IBS and upper gastrointestinal symptoms. New classes of treatments comprising low fermentable oligo-, di-, monosacharides, and polyols diet, probiotics, non-absorbable antibiotics, and secretagogues have good evidence base for their efficacy. CONCLUSIONS: Our consensus is that all patients with functional gastrointestinal disorders should be evaluated comprehensively with a view to holistic management. Physicians should be encouraged to take a positive attitude to the treatment outcomes for IBS patients.

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases

BACKGROUND/AIMS: To examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort. METHODS: A prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD. RESULTS: Three hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77–3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049). CONCLUSIONS: In this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users.

Advances in Diagnosis and Treatment of Sphincter of Oddi Dysfunction / 胃肠病学

Sphincter of Oddi dysfunction (SOD)is a functional gastrointestinal disorder manifesting with the main symptoms of abdominal pain,abnormal liver function and recurrent idiopathic acute pancreatitis,which involved the abnormal contraction of sphincter of Oddi. The incidence of SOD has been increasing in recent years. More attention should be paid on SOD for decreasing the misdiagnosis in clinical practice. This article reviewed the recent advances in diagnosis and treatment of SOD.

Value of intracavitary contrast-enhanced ultrasound via abdomen in fistulas difficult to diagnose before operation / 中国医师杂志

Objective To evaluate the value of intra-cavitary contrast-enhanced ultrasound (IC-CEUS) via abdomen in fistulas difficult to diagnose before operation.Methods Clinical data of 12 patients with preoperative clinical suspicion of Crohn's Disease (CD) complications of fistula were enrolled in the study.Colonoscopy,cystoscope,or CT/MR has not confirmed the diagnosis of intra abdominal fistulas.IC-CEUS were performed by locally-injection of contrast agent in abdominal abscess,observing fistula and the relationship with the adjacent organs in CEUS mode.Diagnostic criteria were surgical findings.Results Fistulas in 10 patients were detected by IC-CEUS,including 7 cases of Ileo-mesenteric fistuls,2 cases of il eo-vesical fistulas,and 1 case of colo-vesical fistula.The accuracy rate of IC-CEUS in diagnosis of fistulas difficult to diagnose before operation in Crohn's disease was 83.3％ (10/12).No severe adverse events occurred during and after IC-CEUS procedure.Conclusions Our preliminary study shows that IC-CEUS is feasible in detecting abdominal fistula with high accuracy.It might be used as the alternative imaging tech nique for detecting fistulas when CT and MR are insufficient.

Prognostic value of carcinoembryonic antigen, alpha fetoprotein, carbohydrate antigen 125 and carbohydrate antigen 19-9 in gastroenteropancreatic neuroendocrine neoplasms / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the rate of elevated common biomarkers of digestive tumors, including carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9), in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) and their prognostic values in GEP-NEN.</p><p><b>METHODS</b>Clinicopathological data of patients with GEP-NEN treated in The First Affiliated Hospital, Sun Yat-sen University from January 2011 to December 2016 were retrospectively studied. The inclusion criteria were as follows: patients with complete clinicopathological data including AFP, CEA, CA125 and CA19-9 level before treatment; patients without previous or other concomitant cancer; patients diagnosed as sporadic but not familial NEN. Serum AFP level >30 μg/L, CEA level >7.5 μg/L, CA125 level >52.5 μg/L and CA19-9 level >52.5 kU/L were defined as elevation respectively. Kaplan-Meier analysis and Log-rank test were applied to investigate the prognostic role of these biomarkers.</p><p><b>RESULTS</b>A total of 170 patients with GEP-NEN were enrolled, and 105 (61.8%) patients were male with median age of 52.5 years. Thirty-six (21.2%), 77 (45.3%) and 57 (33.5%) cases were gastric, intestinal and pancreatic NEN respectively. Elevated AFP, CEA, CA125 and CA19-9 were found in 3(1.8%), 19(11.2%), 22(12.9%) and 21(12.4%) patients. Elevated CEA was related with G3 disease (OR=4.78, 95%CI:1.28-17.85, P=0.020) and elevated CA125 was related with distant metastasis (OR=51.60, 95%CI:5.76-462.44, P=0.000) while elevated CA19-9 was related with both G3 disease (OR=3.81; 95%CI:1.21-11.99, P=0.022) and distant metastasis(OR=4.87; 95%CI:1.41-16.75, P=0.012). The median follow-up was 22.5 months. Forty-six patients (27.1%) died during the follow-up. Patients with elevated CEA, CA125 or CA19-9 had worse overall survival compared with their counterparts with the median survivals of 14 months (95%CI:5.4 to 22.6 months, χ=15.582, P=0.000), 6 months (95%CI:3.2 to 8.8 months, χ=37.627, P=0.001) and 10 months (95%CI:0 to 20.6 months, χ=50.187, P=0.000) respectively. Furthermore, patients with more than two elevated biomarkers (median survival 6 months, 95%CI:4.37-7.63 months) had worse survival than patients with only one elevated biomarker (median survival 26 months, 95%CI:15.68-36.32 months, χ=9.295, P=0.002).</p><p><b>CONCLUSIONS</b>Elevation of AFP, CEA, CA125 or CA19-9 is not common in GEP-NEN. Patients with elevation of these biomarkers have poor survival.</p>

Advances in Medical Treatment for Pancreatic Neuroendocrine Neoplasms / 胃肠病学

Pancreatic neuroendocrine neoplasm (pNEN)is a kind of rare neoplasms with high heterogeneity.Surgery is the first choice to cure local resectable tumor.However,for patients with local advanced tumor or distant metastasis, medical treatment is the main option. Medical treatment mainly encompasses biotherapy, targeted therapy and chemotherapy.Clinicians should make therapeutic option for patients based on the functional status and somatostatin receptor status of the tumor,tumor grade,tumor stage and drug toxicity profile.

Mechanism of Involvement of Intestinal Microbiota in Pathogenesis of Irritable Bowel Syndrome / 胃肠病学

The etiology and pathogenesis of irritable bowel syndrome (IBS) are not fully understood, and intestinal microbiota had been assumed as a possible factor in the pathogenesis of IBS.Increasing evidences have shown that alterations of gut microbiota were found in IBS patients and modulation of intestinal microbiota might be effective in the treatment of IBS.This article reviewed the mechanism of involvement of intestinal microbiota in pathogenesis of IBS by altering mucosal permeability, activating immune reaction, disturbing gastrointestinal motility and affecting brain-gut axis.

Advances of circulating biomarkers in gastroenteropancreatic neuroendocrine neoplasms / 中华胃肠外科杂志

Gastroenteropancreatic neuroendocrine neoplam (GEP-NEN) is a rare group of tumors with its incidence rising significantly in recent decades. Because of the late presentation of the disease and limitations in conventional biomarkers, about 50% of GEP-NEN patients manifests advanced disease when diagnosed. Therefore, it is vital to identify circulating biomarkers which can not only be used for early diagnosis but also accurately evaluating the biological behavior of GEP-NEN. This review summarizes the advances of circulating biomarkers in diagnosing and evaluating efficacy of treatment in GEP-NEN. Well-known circulating biomarkers include chromogranin A (CgA), pancreastatin (PST), chromogranin B (CgB), neuron-specific enolase (NSE) and pancreatic peptide(PP). Novel biomarkers including circulating tumor cell(CTC), microRNA and NETest are promising biomarkers with potential clinical benefit, but further researches are needed before their clinical applications.

Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinical epidemiology change trend of upper gastrointestinal bleeding (UGIB) over the past 15 years.</p><p><b>METHODS</b>Consecutive patients who was diagnosed as continuous UGIB in the endoscopy center of The First Affiliated Hospital of Sun-Yat University during the period from 1 January 1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013 were enrolled in this study. Their gender, age, etiology, ulcer classification, endoscopic treatment and hospitalization mortality were compared between two periods.</p><p><b>RESULTS</b>In periods from 1997 to 1998 and 2012 to 2013, the detection rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(χ=360.089, P=0.000); the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092) (χ=0.179, P=0.672), and the onset age was (47.3±16.4) years and (51.4±18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first etiology of UGIB was peptic ulcer bleeding, accounting for 65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB, but the ratio obviously decreased to 52.7%(575/1092)(χ=32.467, P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of duodenal ulcer bleeding was the main reason (χ=53.724, P=0.000). Esophageal and gastric varices bleeding became the second cause (15.1%,165/1 092, χ=38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092, χ=3.352, P=0.067). The largest increasing amplitude of the onset age was peptic ulcer bleeding [(46.2±16.7) years vs. (51.9±18.9) years, t=-5.548, P=0.000), and the greatest contribution to the amplitude was duodenal ulcer bleeding [(43.4±15.9) years vs. (48.4±19.4) years, t=-3.935, P=0.000], while the onset age of esophageal and gastric varices bleeding [(49.8±14.1) years vs. (48.8±13.9) years, t=0.458, P=0.648] and cancer [(58.4±13.4) years vs. (58.9±16.7) years, t=-0.196, P=0.845] did not change significantly. Compared with the period from 1997 to 1998, the detection rate of high risk peptic ulcer rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (χ=39.958, P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6% (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the achievement ratio of hemostasis was 96.9%(253/261), which was significantly higher (χ=23.287, P=0.000). Compared to the period from 1997 to 1998, more patients with variceal bleeding or non-variceal bleeding received endoscopic treatment in time (39.0% vs. 70.3%, χ=51.930, P=0.000; 3.6% vs. 15.6%, χ=62.292, P=0.000, respectively), and higher ratio of patients staging Forrest stage I(a to II(b also received endoscopic treatment in the period from 2012 to 2013 [27.4%(26/95) vs. 68.5%(111/162), χ=40.739, P=0.000]. More qualified endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs. 15.2%, χ=79.518, P=0.000), hemostatic clip (0 vs. 55.9%, χ=20.879, P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%, χ=5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%, χ=10.420, P=0.001), and single spraying for hemostasis was completely abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs. 6.0%(65/1092), χ=7.970, P=0.005], while no significant difference was found in mortality during hospitalization between two periods.</p><p><b>CONCLUSION</b>Compared with the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the cure rate of endoscopic treatment for UGIB increased, more reasonable and immediate hemostatic methods were used, but overall mortality did not change obviously in the period from 2012 to 2013.</p>

Assessment of the Asian Neurogastroenterology and Motility Association Chronic Constipation Criteria: An Asian Multicenter Cross-sectional Study

BACKGROUND/AIMS: There is a need for a simple and practical tool adapted for the diagnosis of chronic constipation (CC) in the Asian population. This study compared the Asian Neurogastroenterology and Motility Association (ANMA) CC tool and Rome III criteria for the diagnosis of CC in Asian subjects. METHODS: This multicenter, cross-sectional study included subjects presenting at outpatient gastrointestinal clinics across Asia. Subjects with CC alert symptoms completed a combination Diagnosis Questionnaire to obtain a diagnosis based on 4 different diagnostic methods: self-defined, investigator's judgment, ANMA CC tool, and Rome III criteria. The primary endpoint was the level of agreement/disagreement between the ANMA CC diagnostic tool and Rome III criteria for the diagnosis of CC. RESULTS: The primary analysis comprised of 449 subjects, 414 of whom had a positive diagnosis according to the ANMA CC tool. Rome III positive/ANMA positive and Rome III negative/ANMA negative diagnoses were reported in 76.8% and 7.8% of subjects, respectively, resulting in an overall percentage agreement of 84.6% between the 2 diagnostic methods. The overall percentage disagreement between these 2 diagnostic methods was 15.4%. A higher level of agreement was seen between the ANMA CC tool and self-defined (374 subjects [90.3%]) or investigator’s judgment criteria (388 subjects [93.7%]) compared with the Rome III criteria. CONCLUSION: This study demonstrates that the ANMA CC tool can be a useful for Asian patients with CC.

Esophagogastric Junction Contractility Integral Reflect the Anti-reflux Barrier Dysfunction in Patients with Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Anti-reflux barrier dysfunction is one of the primary mechanisms in gastroesophageal reflux disease (GERD) pathogenesis. The esophagogastric junction contractile integral (EGJ-CI) is a new metric adopted to evaluate the EGJ contractility, which implies the anti-reflux barrier function. The aim of the current study was to validate this new metric in patients with GERD and its correlation with the esophageal acid exposure, as well as the efficacy of proton pump inhibitor treatment. METHODS: Ninety-eight patients with GERD and 21 healthy controls were included in the study. Upper endoscopy, high-resolution manometry (HRM) and 24-hour multichannel intraluminal impedance-pH monitoring were performed in all patients. Three respiration cycles were chosen at the initial HRM resting frame and the value computed with distal contractile integral tool was then divided by the duration of the cycles to yield EGJ-CI. All the patients were treated with esomeprazole 20 mg twice-daily for 8 weeks. RESULTS: EGJ-CI was lower in the patients with GERD than that of the controls (P < 0.05). For patients with GERD, EGJ-CI was lower in those with hiatal hernia (P < 0.05). The new metric correlated with esophageal acid exposure in the supine position (P < 0.05), and it also negatively correlated to the total reflux episodes (P < 0.05). There was no significant difference on EGJ-CI between patients with and without response to the esomeprazole treatment (P = 0.627). CONCLUSIONS: EGJ-CI reflected the dysfunction of the anti-reflux barrier in patients with GERD, but it had little impact on the esomeprazole response.

Relationship Between Salivary Pepsin Concentration and Esophageal Mucosal Integrity in Patients With Gastroesophageal Reflux Disease

BACKGROUND/AIMS: Increased salivary pepsin could indicate an increase in gastro-esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients. METHODS: A total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: The IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035). CONCLUSIONS: We confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS.

Clinicopathological characteristics and prognosis analysis of colorectal neuroendocrine neoplasms based on the data from domestic six medical centers / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and their relationship with prognosis of colorectal neuroendocrine neoplasms (NEN).</p><p><b>METHODS</b>Medical records of 329 patients with colorectal NEN between June 2001 and July 2016 from 6 large scale centers in China were reviewed to investigate the clinicopathological characteristics and their relationship with prognosis of colorectal NEN.</p><p><b>RESULTS</b>(1) Colonic NEN: A total of 41 patients with colonic NEN were enrolled from The First Affiliated Hospital of Sun Yat-sen University(n=11), Sun Yat-sen University Cancer Center (n=15), Guangdong General Hospital (n=10), Sun Yet-san Memorial Hospital of Sun Yat-sen University (n=3) and Fudan University Shanghai Cancer Center (n=2). 41 cases, including 20 males and 21 females with a mean age of (58.7±4.7) years. Twenty-three colonic NEN originated in hindgut (23/41, 56.1%), and 20 patients were stage IIII( (20/41, 48.8%). Nine cases (22.0%) were neuroendocrine tumor(NET), 25(61.0%) were neuroendocrine carcinoma (NEC) and 7(17.1%) were mixed adenoendocrine carcinoma (MANEC). Six cases (14.6%) were G1 grade, 3(7.3%) were G2 grade and 32(78.1%) were G3 grade. Ulcerative or cauliflower-like tumors were the most common appearance under endoscopy (both 9/41, 22.0%). Thirty-three patients (80.5%) underwent surgery. During follow-up, 19 cases died and the 3-year survival rate was 46.1%. Multivariate analysis revealed that stage IIII( was an independent risk factor of poor prognosis (HR=3.871, 95%CI:1.342 to 11.167, P=0.012) in colonic NEN patients. (2) Rectal NEN: A total of 288 patients with rectal NEN were enrolled from The First Affiliated Hospital of Sun Yat-sen University(n=130), Nanfang Hospital of Southern Medical University (n=115) and Fudan University Shanghai Cancer Center (n=43). Two hundred and eighty-eight cases, including 181 males and 107 females with a mean age of (47.7±1.5) years. One hundred and ninety-seven patients were stage I((197/288, 68.4%). Of 288 rectal NEN cases, 267(92.7%) were NET, 20(7.0%) were NEC and 1(0.3%) was MANEC; 214(74.3%) were G1 grade, 53(18.4%) were G2 grade and 21(7.3%) were G3 grade. Submucosal tumor was the most common appearance under endoscopy(164/288, 56.9%). Most of the rectal NET G1/G2 tumors were submucosal(146/214, 68.2%;18/53,34.0% respectively) while most of G3 tumors were cauliflower-like (14/21,66.7%). A total of 175 patients (60.8%) underwent endoscopic therapy, while 96 patients(33.3%) underwent surgery. During follow-up, 12 cases died and 3-year survival rate was 94.0%. Multivariate analysis revealed that poor differentiation as NEC or MANEC(HR=8.919, 95% CI:1.911 to 41.637, P=0.005) and stage III( to IIII((HR=10.304, 95%CI:1.772 to 59.916, P=0.009) were independent risk factors of poor prognosis in rectal NEN patients.</p><p><b>CONCLUSIONS</b>The clinicopathological manifestations of rectal NEN and colonic NEN are quite different. Rectal NEN are more common with better differentiation and has better prognosis than colonic NEN.</p>