Irritable bowel syndrome:Emerging paradigm in pathophysiology

Irritable bowel syndrome(IBS)is one of the most common gastrointestinal disorders,characterized by abdominal pain,bloating,and changes in bowel habits.These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS.Therefore,IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination.Although a great deal of research has been carried out in this area,the pathophysiology of IBS is complex and not completely understood.Multiple factors are thought to contribute to the symptoms in IBS patients;altered gastrointestinal motility,visceral hypersensitivity,and the brain-gut interaction are important classical concepts in IBS pathophysiology.New areas of research in this arena include inflammation,postinfectious low-grade inflammation,genetic and immunologic factors,an altered microbiota,dietary factors,and enteroendocrine cells.These emerging studies have not shown consistent results,provoking controversy in the IBS field.However,certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients,confirming that IBS symptoms cannot be explained by a single etiological mechanism.Therefore,it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms.

Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus

AIM To investigate histologic abnormalities in the gastric smooth muscle of patients with diabetes mellitus(DM).METHODS Full-thickness gastric specimens were obtained from patients undergoing surgery for gastric cancer. H&E stain and Masson's Trichrome stain were performed to assess the degree of fibrosis. Immunohistochemical staining using various antibodies was also performed [antibodies against protein gene product 9.5(PGP9.5), neuronal nitric oxide synthase(n NOS), vasoactive intestinal peptide(VIP), neurokinin-1(NK1) receptor, c-Kit, and platelet-derived growth factor receptor-alpha,(PDGFRα)]. Immunofluorescent staining and evaluation with confocal microscopy were also conducted.RESULTS Twenty-six controls and 35 diabetic patients(21 shortduration patients and 14 long-duration patients) were included. There were no significant differences in basic demographics between the two groups except in mean body mass index(BMI)(higher in the DM group). Proportions of moderate-to-severe intercellular fibrosis in the muscle layer were significantly higher in the DM group than in the control group(P < 0.01). On immunohistochemical staining, c-Kit- and PDGFRα-positive immunoreactivity were significantly decreased in the DM group compared with the control group(P < 0.05). There were no statistically significant differences in PGP9.5, n NOS, VIP, and neurokinin 1 expression. On immunofluorescent staining, cellularity of interstitial cells of Cajal(ICC) was observed to decrease with increasing duration of DM.CONCLUSION Our study suggests that increased intercellular fibrosis, loss of ICC, and loss of fibroblast-like cells are found in the smooth muscle of DM patients. These abnormalities may contribute to changes in gastric motor activity in patients with DM.

Risk factors for local recurrence after en bloc endoscopic submucosal dissection for early gastric cancer

AIM: To investigate factors related to recurrence following en bloc resection using endoscopic submucosal dissection(ESD) in patients with early gastric cancer(EGC). METHODS: A total of 1121 patients(1215 lesions) who had undergone ESD for gastric neoplasia between April 2003 and May 2010 were retrospectively reviewed. Data from 401 patients(415 lesions) were analyzed, following the exclusion of those who underwent piecemeal resection, with deep resection margin invasion or lateral margin infiltration, and diagnosed with benign lesions. RESULTS: Local recurrence after en bloc ESD was found in 36 cases(8.7%). Unclear resection margins, long procedure times, and narrow safety margins were identified as risk factors for recurrence. Lesions located in the upper third of the stomach showed a higher rate of recurrence than those located in the lower third of the stomach(OR = 2.9, P = 0.03). The probability of no recurrence for up to 24 mo was 79.9% in those with a safety resection margin ≤ 1 mm and 89.5% in those with a margin > 1 mm(log-rank test, P = 0.03). CONCLUSION: Even in cases in which en bloc ESD is performed for EGC, local recurrence still occurs. To reduce local recurrences, more careful assessment will be needed prior to the implementation of ESD in casesin which the tumor is located in the upper third of the stomach. In addition, clear identification of tumor boundaries as well as the securing of sufficient safety resection margins will be important.

Significant risk and associated factors of active tuberculosis infection in Korean patients with inflammatory bowel disease using anti-TNF agents

AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.

Prediction of the indication criteria for endoscopic resection of early gastric cancer

AIM: To find risk factors of lymph node metastasis(LNM) in early gastric cancer(EGC) and to find proper endoscopic therapy indication in EGC.METHODS: We retrospectively reviewed the 2270 patients who underwent curative operation for EGC from January 2001 to December 2008. EGC was defined as malignant lesions that do not invade beyond the submucosal layer of the stomach wall irrespective of presence of lymph node metastasis.RESULTS: Among 2270 enrolled patients, LNM was observed in 217(9%) patients. LNM in intramucosal(M) cancer and submucosal(SM) cancer was detectedin 3 8( 2. 8 %, 3 8 / 1 3 4 0) patients and 1 7 9(19%, 179/930) patients, respectively. In univariate analysis, the risk factors for LNM in EGC were size of tumor, Lauren classification, ulcer, lymphatic invasion, vascular invasion, and depth of invasion. However, in multivariate analysis, size of tumor, lymphatic invasion, vascular invasion, and depth of invasion were risk factors for LNM in EGC. Size of tumor, lymphatic invasion, vascular invasion, and depth of invasion were risk factors for LNM in cases of intramucosal cancer and submucosal cancer. In particular, there was no lymph node metastasis in cases of well differentiated early gastric cancer below 1 cm in size without ulcer regardless of lymphovascular invasion.CONCLUSION: Tumor size, perilymphatic-vascular invasion, and depth of invasion were risk factors for LNM in EGC. There was no LNM in EGC below 1 cmregardless risk factors.

Comparison of a novel bedside portable endoscopy device with nasogastric aspiration for identifying upper gastrointestinal bleeding

AIM: To compare outcomes using the novel portable endoscopy with that of nasogastric(NG) aspiration in patients with gastrointestinal bleeding.METHODS: Patients who underwent NG aspiration for the evaluation of upper gastrointestinal(UGI) bleeding were eligible for the study. After NG aspiration, we performed the portable endoscopy to identify bleeding evidence in the UGI tract. Then, all patients underwent conventional esophagogastroduodenoscopy as the gold-standard test. The sensitivity, specificity, and accuracy of the portable endoscopy for confirming UGI bleeding were compared with those of NG aspiration.RESULTS: In total, 129 patients who had GI bleedingsigns or symptoms were included in the study(age 64.46 ± 13.79, 91 males). The UGI tract(esophagus, stomach, and duodenum) was the most common site of bleeding(81, 62.8%) and the cause of bleeding was not identified in 12 patients(9.3%). Specificity for identifying UGI bleeding was higher with the portable endoscopy than NG aspiration(85.4% vs 68.8%, P = 0.008) while accuracy was comparable. The accuracy of the portable endoscopy was significantly higher than that of NG in the subgroup analysis of patients with esophageal bleeding(88.2% vs 75%, P = 0.004). Food material could be detected more readily by the portable endoscopy than NG tube aspiration(20.9% vs 9.3%, P = 0.014). No serious adverse effect was observed during the portable endoscopy.CONCLUSION: The portable endoscopy was not superior to NG aspiration for confirming UGI bleeding site. However, this novel portable endoscopy device might provide a benefit over NG aspiration in patients with esophageal bleeding.

Successful endoscopic submucosal dissection of a giant polyp in a 21-month-old female

Endoscopic submucosal dissection(ESD)is now recognized as the preferred treatment modality for gastrointestinal epithelial lesions.A 21-month-old female was admitted with a giant hyperplastic polyp causing a gastric outlet obstruction.Successful ESD was performed with caution.The post-procedural course was uneventful without a bleeding episode.Although further study of the feasibility of ESD in early children is necessary,ESD could be applied to avoid laparotomy even in young children.

Negative impact of sedation on esophagogastric junction evaluation during esophagogastroduodenoscopy

AIM:To compare the esophagogastric junction(EGJ)areas observed in sedated and non-sedated patients during esophagogastroduodenoscopy(EGD).METHODS:Data were collected prospectively from consecutive patients who underwent EGD for various reasons.The patients were divided into three groups according to the sedation used:propofol,midazolam,and control(no sedation).The EGJ was observed during both insertion and withdrawal of the endoscope.The extent of the EGJ territory observed was classified as excellent,good,fair,or poor.In addition,the time the EGJ was observed was estimated.RESULTS:The study included 103 patients(50 males;mean age 58.44±10.3 years).An excellent observation was achieved less often in the propofol and midazolam groups than in the controls(27.3%,28.6%and91.4%,respectively,P<0.001).There was a significant difference in the time at which EGJ was observed among the groups(propofol 20.7±11.7 s vs midazolam 16.3±7.3 s vs control 11.6±5.8 s,P<0.001).Multivariate analysis showed that sedation use was the only independent risk factor for impaired EGJ evaluation(propofol,OR=24.4,P<0.001;midazolam,OR=25.3,P<0.001).Hiccoughing was more frequent in the midazolam group(propofol 9%vs midazolam25.7%vs control 0%,P=0.002),while hypoxia(SaO2<90%)tended to occur more often in the propofol group(propofol 6.1%vs midazolam 0%vs control 0%,P=0.101).CONCLUSION:Sedation during EGD has a negative effect on evaluation of the EGJ.

Randomized controlled trial to evaluate the efficacy and safety of fexuprazan compared with esomeprazole in erosive esophagitis

BACKGROUND Fexuprazan,a novel potassium-competitive acid blocker,reversibly suppresses the K+/H+-ATPase enzyme in proton pumps within gastric parietal cells.Fexuprazan’s suppression of gastric acid was maintained in healthy individuals for 24 h in a dose-dependent manner.AIM To compare fexuprazan to esomeprazole and establish its efficacy and safety in patients with erosive esophagitis(EE).METHODS Korean adult patients with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg or esomeprazole 40 mg once daily for eight weeks.The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy at week 8.The secondary endpoints included the healing rate of EE at week 4,symptom response,and quality of life assessment.Safety profiles and serum gastrin levels were compared between the groups.RESULTS Of the 263 randomized,218 completed the study per protocol(fexuprazan 40 mg,n=107;esomeprazole 40 mg,n=111).Fexuprazan was non-inferior to esomeprazole regarding the healing rate at week 8[99.1%(106/107)vs 99.1%(110/111)].There were no between-group differences in the EE healing rate at week 4[90.3%(93/103)vs 88.5%(92/104)],symptom responses,and quality of life assessments.Additionally,serum gastrin levels at weeks 4 and 8 and drug-related side effects did not significantly differ between the groups.CONCLUSION Fexuprazan 40 mg is non-inferior to esomeprazole 40 mg in EE healing at week 8.We suggest that fexuprazan is an alternative promising treatment option to PPIs for patients with EE.