Objectives: The precipitating mechanism(s) from the inactive to the active stage of duodenal ulcer disease (DU) is unclear. It has been shown that hydrogen gas from colonic fermentation provides an important energy source for Helicobacter pylori (Hp) colonization. The lactulose hydrogen breath test (LHBT) is a useful tool to assess the small intestinal and/or colon fermentation. This study examines the association(s) between the status of gastroduodenal disease and the result of a lactulose hydrogen breath test (LHBT). Materials and Methods: We enrolled Hp-positive active duodenal ulcer (aDU) patients, inactive DU (iDU) patients and patients with a positive Hp infection without structural gastroduodenal lesion, i.e., simple gastritis (SG Hp+). The patients with simple gastritis without Hp infection (SG Hp−) served as controls. Histological examinations of the gastric mucosa and lactulose hydrogen breath test (LHBT) were performed. Results: SG Hp+ patients tend to have advanced gastritis (pangastritis or corpus-predominant gastritis) compared with SG Hp− patients (7/29 vs. 0/14, p = 0.08). More iDU patients had advanced gastritis than either the SG Hp+ (7/9 vs. 7/29, p = 0.006) or aDU patients (7/9 vs. 6/24, p = 0.013). In comparison with the aDU patients, the iDU patients were also older (52.1 ± 12.6 vs. 42.2 ± 11.9 years, p = 0.02) and had a lower mean area under the curve value of the LHBT(AUC) (209.1 ± 86.0 vs. 421.9 ± 70.9, p = 0.023). Conclusion: aDU patients with a positive Hp infection have a lower grade of gastric mucosa damage than iDU patients and tend to have a higher level of exhaled hydrogen after LHBT.
Background: Endoscopic submucosal dissection is minimal invasive endoscopic procedure to deal with gastric tumor. Initially, it was developed to resect mucosal neoplasm since 2000 and extended its application to submucosal tumor in the following years. Although the basic ESD skills are similar in gastric mucosal tumor and subepithelial tumor, the success rate, complication may be different between the two types of gastric tumor resection. This retrospective study is conducted to analyze the ESD procedure in gastric mucosal tumor and subepithelial tumor. Methods: From 2007 to 2016, we reviewed all patients who underwent endoscopic submucosal dissection for gastric mucosal tumor and subepithelial tumor in Kaohsiung Medical University Hospital. Results: Totally, 35 patients with gastric subepithelial tumor and 41 patients with gastric mucosal tumor received endoscopic submucosal dissection are enrolled. Among 35 patients with subepithelial tumor, 32 (91.4%) patients achieved curative treatment. 1 patient received emergent operation and 2 patients received salvage operation to complete tumor resection. 8 patients (22.9%) occurred perforation and no delay bleeding was found. Among 41 patients with mucosal neoplasm, 30 (71.4%) patients achieved curative treatment. 2 patients received emergent operation and 9 patients received salvage operation to complete tumor resection. 9 patients (21.9%) occurred complication, 6 patients occurred delay bleeding and 3 patients had perforation. Conclusions: Comparing ESD between gastric mucosal tumor and subepithelial tumor, ESD had similar efficiency in curative treatment. However, ESD in subepethelial tumor encountered higher perforation and lesser delay bleeding.
Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.
Background and Aim Asian populations have relatively lower prevalence of gastroesophageal reflux disease and tend to exhibit symptoms of prolonged gastric retention. However, it remains unknown if slower gastric emptying influences its features in Asian countries. We prospectively assessed the potential implications of slower gastric emptying in an Asian-Pacific cohort of gastroesophageal reflux disease by a hospital-based survey. Methods One hundred fifty-two patients of gastroesophageal reflux disease complete the scintigraphic measurement of solid phase of gastric emptying. Clinical symptoms and psychological stress are recorded by self-report questionnaire. The status of Helicobacter pylori infection, blood level of pepsinogen I, and I/II ratio are assessed. Results Forty-seven percent and 28% of the patients have slower gastric emptying rate, depending on the incremental defined cut-off values of slower gastric emptying, respectively. Multiple logistic regression analysis indicates that older age and depression score are independently related to slower gastric emptying. Subgroup analysis discloses that patients with slower gastric emptying and higher depression score tend to present with non-erosive esophagitis whereas higher body mass index level and male gender in patients with normal gastric emptying predict the presence of erosive reflux disease. Conclusions Our study cohort of Asian patients indicates distinctive clinical implications of slower gastric emptying in patients with gastroesophageal reflux disease.
Mis-swallowed foreign body is a common scenario for endoscopy intervention. Although a long object is rarely seen in our clinical setting, limited published articles could be found for proper retrieval. We hence report a 30-year-old female who mis-swallowed a long table spoon, which was retrieved by a snare from the duodenal second portion with conventional endoscopy.
Gastric antral vascular ectasia (GAVE) is an uncommon but important cause of chronic gastrointestinal bleeding. It is often associated with systemic diseases such as autoimmune diseases, liver cirrhosis, chronic renal insufficiency and cardiovascular disease. The etiology of GAVE has not been fully explored and remains controversial. Diagnosis is mainly based on endoscopic presentation with flat or raised erythematous stripes radiating from the pylorus to the antrum and resembles a watermelon. Clinical presentation may range from iron-deficiency anemia secondary to occult blood loss, melena to hematemesis. In past decades, many therapeutic modalities including medical, endoscopic and surgical intervention have been introduced for GAVE treatment with variable efficacy. Herein, we review the efficacy and safety of these treatment options for GAVE.
Dear Editor, Endometriosis related dysmenorrhea, deep dyspareunia, dyschezia and dysuria are not uncommon among fertile women. Frequently noted anatomic distribution of endometriosis includes ovary, cul-de-sac, and uterus [1]. However, gastrointestinal (GI) tract endometriosis is rarely found. Here we report a case of recto-sigmoid mass relate to endometriosis. This 43-year-old woman with past history of chocolate cyst post excision presented with intermittent bloody stool passage for 2 months. She also had the symptoms of left lower abdominal pain and decreased frequency of stool passage. Her abdominal pain was not related to food intake and stool passage. Bloody stool episode occurred especially during her menstrual cycle. Except for tenderness over left lower abdomen, physical examination including rectal digital examination was unremarkable. Colonoscopy examination revealed a sessile mass occupied about 1/3 circumferential lumen. The mucosa was eroded and with subtle color changes, from 8 cm to 15 cm above the anal verge (Fig. 1A). Endoscopic biopsy showed benign rectal mucosa with chronic inflammatory infiltration in the edematous lamina propria. Contrast computed tomography of the abdomen showed thickening colonic wall along the recto-sigmoid area extending about 7.0 cm in length (Fig. 1B). Blood examinations including CEA level were within normal range. (A) Colonoscopy revealed a sessile mass occupied about 1/3 circumferential lumen with subtle color changes and mucosa erosion (white arrows). (B) Computed tomography of the abdomen survey disclosed wall thickening at the recto-sigmoid colon (white arrows). (C) Operation picture showed total obliteration of Cou-de-sac, the deep infiltrating endometriosis (asterisk) was extended over bilateral uterosacral ligaments and rectum. (D) Endometrial tissue is noted at submucosa (yellow arrow) near the colon mucosal base (100×). Laparoscopic intervention showed a long segment of submucosal lesion along rectum with lumen stricture and bloody ascites (Fig. 1C). Low anterior resection and end-to-side colo-colostomy were performed subsequently. Microscopically, the colon tissue showed multiple embedded foci of endometrial tissue including both glandular and stromal parts in submucosa, muscular wall and subserosal fibroadipose tissue (Fig. 1D). Endometriosis implants to GI tract consist about 5.4% of all endometriosis. The most involving area is rectum (about 70–80%), and followed by sigmoid, appendix, and terminal ileum [2]. The most common symptoms of recto-sigmoid endometriosis are bowel habit change, abdominal pain, and hematochezia. These symptoms may mimic malignancy, inflammatory bowel disease, or ischemic colitis, which pose the difficulties to accurate diagnosis. There is no gold standard for the non-invasive diagnosis of GI involvement of endometriosis. Computed tomography with distention of the colon by rectal enterolysis (MSCTe) may present enhanced solid nodules, contiguous or penetrating the colonic wall, but the depth infiltrated by nodules may be underestimated [3]. Colonfiberscopic examination may appear polyps or masses, thickened wall, mucosa change with erythema or granularity, and even narrowing of the bowel lumen. However, it is difficult to distinguish from malignancy if endometriosis only invades submucosa layer. Kim et al. reported five cases of endometriosis present with fungating ulcerative colonic mass with non-specific biopsy findings [4]. Milone et al. have shown low diagnosis rate of bowel endometriosis by colonoscopy [5]. However, close infiltration of the endometrial tissue to the mucosa layer, as shown in this patient, implicates the potential diagnostic yield of full thickness biopsy by large biopsy forceps before invasive intervention. Laparoscopy or laparotomy is usually the definite diagnostic procedure and treatment of endometriosis. During the operation, surgeons can make complete evaluation of genital and intestinal endometriosis and get tissue proof for accurate diagnosis. Major complications included rectovaginal fistula, rectosigmoid anastomosis dehiscence and bowel occlusion. Endometriosis presented with recto-sigmoid mass was an uncommon finding. It is important to consider this association in a fertile female patient with recurrent abdominal pain, defecation abnormality and bloody stool.
Miniprobe endoscopic ultrasound (miniprobe EUS) has been used as the staging tool in upper gastrointestinal neoplasms, including esophageal cancer and gastric cancer. Staging results have a strong impact on the decision as to whether a patient should undergo endoscopic treatment, surgery alone, or neoadjuvant therapy. This retrospective study was conducted to analyze the accuracy of miniprobe EUS in staging of gastric cancer and esophageal cancer. From January 2007 to August 2011, 71 patients who underwent EUS with 12-MHz miniprobe for staging of esophageal cancer or gastric cancer before endoscopic submucosal dissection or surgical esophagectomy, or gastrectomy plus lymphadenectomy, were included. Seventy-one consecutive patients, 35 with esophageal cancer and 36 with gastric cancer, were included in this study. In the 35 esophageal cancer cases, 22 patients underwent surgical esophagectomy plus lymphadenectomy and 13 patients underwent endoscopic submucosal dissection. Postoperatively, 20 patients were staged as having T1 cancers (57.1%), eight patients T2 (22.9%), six patients T3 (17.1%), and one patient T4 (2.9%). The accuracy of miniprobe EUS to the T stage was 91.4% for T1, 71.4% for T2, 80% for T3, and 82.9% for T4, respectively. Positive lymph nodes were diagnosed histologically in four patients among 22 extensive esophagectomy patients (18.2 %). The accuracy of miniprobe EUS for the diagnosis of lymph node was 50% for esophageal cancer. Among the 36 gastric cancer patients, 32 underwent surgical gastrectomy plus D2 lymphadenectomy and four underwent endoscopic submucosal dissection. Postoperatively, 24 patients were staged as having T1 cancers (66.7%), nine patients T2 (25.0%), two patients T3 (5.6%), and one patient T4 (2.7 %). The accuracy of miniprobe EUS relative to the T stage was 66.7% for T1, 55.6% for T2, 91.7% for T3, and 97.2% for T4, respectively. Positive lymph nodes were diagnosed histologically in eight patients among 32 gastrectomy plus lymphadenectomy. The accuracy of miniprobe EUS for the diagnosis of lymph node was 61% for gastric cancer. The diagnostic accuracy of miniprobe EUS in patients with esophageal cancer was reliable in T1 cancer. However, the lymph node was frequently overstaged. In gastric cancer, the overall accuracy of T-staging was lower than esophageal cancer and frequently overstaged. Besides, gastric metastatic lymph node was easily missed by miniprobe EUS.
Dear Editor, Endoscopic appearance of enlarged or giant gastric folds is known to be the result of diffuse mucosal hypertrophy. Ménétrier disease, acute gastric mucosal lesions, gastric lymphoma, and scirrhous carcinoma are common causes of giant gastric folds. Enlarged gastric folds may result from gastric linitis plastic, i.e. a distinct scirrhous tumor growth pattern with desmoplastic stromal reaction resulting in wall thickening and rigidity and could be caused by gastric cell and hematogenous metastasis of malignant tumor. We report a rare situation in a patient of multiple myeloma with extramedullary spreading that presented with the endoscopic appearance of diffuse enlarged mucosa folds and poor distended lumen from the lower esophagus to the gastric body. An 88-year-old woman was admitted with the complaint of general malaise, poor appetite, progressive dysphagia, nausea with vomiting and black stool passage for several days. Physical examination showed pale conjunctiva. Chest X ray and plain abdomen film were remarkable. Results of laboratory examinations were: WBC count = 20.32 × 109/L, hemoglobin = 9 g/dl, total protein = 5.9 g/dl, albumin = 2.7 g/dl, serum BUN = 30.7 mg/dl and creatinine = 1.51 mg/dl. Urine routine analysis disclosed pyuria (urine WBC = 10–25/HPF). Esophagogastroduodenoscopy (EGD) and abdominal computed tomography (CT) examination were performed after admission (Fig. 1: A, B, C & D). EGD showed large, erosive mucosa folds from the lower esophagus to EC junction resulted in lumen stenosis (A, white arrows) and irregular polypoid enlargement of the mucosa folds and irregular color changes from the gastric body (B, black arrows) to cardia. Abdominal CT showed diffuse, eccentric wall thickening of the lower esophagus (C, white arrow; D, black arrow) and gastric body (C, white arrowhead; D, black arrow head) with lumen stenosis and structural deformity. Pleomorphic cell having eccentrically located nuclei, coarse chromatin and eosinophilic cytoplasm in the lamina propria (E, white arrows) and immune-histologic stains showed positive for CD138 and leukocyte common antigen (LCA) (F, black arrows), and negative for CD20, CD79a, CD3, CD5, CK and CD117. The patho-histological examination and immunochemical survey of the EGD biopsy were shown in D & E parts of Fig. 1. Kappa and lambda immunostains showed kappa light chain restriction. Blood immunoglobulin profile were IgG: 643 mg/dl, IgA: 133 mg/dl and IgM: 946 mg/dl β2 microglobulin level was 1478 μg/dl and immunofixation showed monoclonal IgM kappa gammopathy that were consistent with the pathohistology of gastric specimen. Bone marrow examination showed hypocellular, absent megakaryocyte and increasing plasma cell portion account up to 10%. The chromosome examination didn't disclose abnormality. To our knowledge, MM with diffuse infiltration at the stomach and lower esophagus that resulted in lumen stenosis and dysphagia has not been reported previously. Gutnick et al. [1] described a patient of multiple myeloma presented with infiltrating plasmacytoma associated with endoscopic findings of enlarged mucosa folds and non distensible lumen of the gastric body. A previous treated patient of kappa-light chain multiple myeloma has been noted to have multilobulated submucosal mass with ulceration at the gastric body [2]. Pehlivan et al. reported a rare endoscopic finding of exudate-covered ulcer in the distal esophagus in a 50-year-old woman with dysphagia and the biopsy result showed the involvement of plasma cells consistent with multiple myeloma of IgG kappa subtype [3]. Since lower part of esophagus shared similar lymphatic drainage and blood supply as those of upper body of the stomach, it is conceivable that esophageal involvement of this patient is likely the result of tumor spreading from the stomach to esophagus. The endoscopic appearance of metastatic lesion is indistinguishable from that of gastric linitis plastica. It has been proposed that primary linitis plastic may come from an undifferentiated carcinomas arose from the fundic gland mucosa followed by preferably submucosa infiltration [4]. The mechanism associated with linitis plastic could also be attributed to surrounding fibroblasts synthesize collagen by some paracrine factors secreted from spreading cancer cells [5], either by submucosa invasion from mucosa lesion, or through hematogenous spreading such as metastatic tumor. Supplementary data related to this article can be found at https://doi.org/10.1016/j.kjms.2017.12.013. Supplementary data Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The management of proton pump inhibitor-refractory GERD (rGERD) is a challenge in clinical practice. Since up to one-third of patients with typical GERD symptoms (heartburn and/or acid regurgitation) are not satisfied with proton pump inhibitor (PPI) therapy, new drug development targeting different pathophysiologies of GERD is imperative. At present, no other drugs serve as a more potent acid suppression agent than PPIs. As an add-on therapy, histamine type-2 receptor antagonists, alginates, prokinetics and transient lower esophageal sphincter relaxation inhibitors have some impact on the subgroups of rGERD, but greater effectiveness and fewer adverse effects for widespread use are required. Visceral hypersensitivity also contributes to the perception of GERD symptoms, and neuromodulators including antidepressants play a role in this category. Esophageal pH-impedance monitoring helps to distinguish functional heartburn from true GERD, and psychologic medication and cognitive behavior therapy are further therapy options instead of PPIs.
We present the preliminary experiences with and short-term outcomes of 50 consecutive patients with rectal cancer who underwent preoperative concurrent chemoradiotherapy (CCRT) followed by robotic surgery by using the high dissection and low ligation technique.
Implantable venous access port (IVAP)-related blood stream infections (BSIs) are one of the most common complications of implantable venous ports. The risk factors and pathogens for IVAP-related BSIs are still controversial.
Gastrointestinal (GI) endoscopy is the major technique for diagnosis of GI disease and treatment. Various sedation and analgesia regimens such as midazolam, fentanyl, and propofol can be used during GI endoscopy. The purpose of the study was to compare propofol alone and propofol combination with midazolam and fentanyl in moderate sedation for GI endoscopy. One hundred patients undergoing GI endoscopy were enrolled in this study. All patients received a propofol target-controlled infusion (TCI) to maintain sedation during the procedure. Patients were randomly allocated into either Group P (propofol TCI alone) or Group C (combination of propofol TCI plus midazolam and fentanyl). Dermographic data, anesthetic parameters (sedation regimen, blood pressure, heart rate, and oxygen saturation), procedure parameters (procedure time, colonoscopy, or panendoscopy), propofol consumption, and adverse events (hypoxia, hypotension, and bradycardia) were all recorded. Postprocedural records included recovery time, postoperative adverse events (nausea, vomiting, dizziness, recall, and pain) and satisfaction. The average propofol consumption was 251 ± 83 mg in Group P and 159 ± 73 mg in Group C (p < 0.001). The incidence of transient hypotension was higher in Group P (p = 0.009). The recovery time and discharge time were both shorter in Group C (p < 0.001 and p = 0.006 respectively). Overall, postprocedural adverse events were similar in both groups. The postanesthetic satisfaction was comparable in both groups. TCI of propofol combined with midazolam and fentanyl achieved sedation with fewer hypotension episodes and shorter recovery and discharge time than propofol TCI alone in patients undergoing GI endoscopy.
Increased incidence of erectile dysfunction (ED) has been reported among patients with sleep apnea (SA). However, this association has not been confirmed in a large-scale study. We therefore performed a population-based cohort study using Taiwan National Health Insurance (NHI) database to investigate the association of SA and ED. From the database of one million representative subjects randomly sampled from individuals enrolled in the NHI system in 2010, we identified adult patients having SA and excluded those having a diagnosis of ED prior to SA. From these suspected SA patients, those having SA diagnosis after polysomnography were defined as probable SA patients. The dates of their first SA diagnosis were defined as their index dates. Each SA patient was matched to 30 randomly-selected, age-matched control subjects without any SA diagnosis. The control subjects were assigned index dates as their corresponding SA patients, and were ensured having no ED diagnosis prior to their index dates. Totally, 4,835 male patients with suspected SA (including 1,946 probable SA patients) were matched to 145,050 control subjects (including 58,380 subjects matched to probable SA patients). The incidence rate of ED was significantly higher in probable SA patients as compared with the corresponding control subjects (5.7 vs. 2.3 per 1000 patient-year; adjusted incidence rate ratio = 2.0 [95% CI: 1.8-2.2], p<0.0001). The cumulative incidence was also significantly higher in the probable SA patients (p<0.0001). In multivariable Cox regression analysis, probable SA remained a significant risk factor for the development of ED after adjusting for age, residency, income level and comorbidities (hazard ratio = 2.0 [95%CI: 1.5-2.7], p<0.0001). In line with previous studies, this population-based large-scale study confirmed an increased ED incidence in SA patients in Chinese population. Physicians need to pay attention to the possible underlying SA while treating ED patients.
Gastrointestinal nodular lymphoid hyperplasia is a rare lymphoproliferative state. In children, it is associated with familial immunodeficiency disease but most cases have no obvious etiology. In adults, nodular lymphoid hyperplasia is associated with immunocompromised status, including chemotherapy, acquired immunodeficiency viral infection, organ transplantation, and multiple polypoid lesions are noted in endoscopic findings and sometimes may be confused with family polypoid syndrome. We present a child with histological proof of focal intestinal nodular lymphoid hyperplasia that had a complete image study including negative results of 18F-fluoro-2-deoxyglucose positron emission tomography/computerized tomography analysis.
Different types of proton pump inhibitor (PPI)-based triple therapies could result in different Helicobacter pylori eradication rates. This study aimed to compare the efficacy and safety of rabeprazole-and lansoprazole-based triple therapies in primary treatment of H. pylori infection. From September 2005 to July 2008, 426 H. pylori-infected patients were randomly assigned to receive a 7-day eradication therapy with either rabeprazole 20 mg bid (RAC group, n = 222) or lansoprazole 30 mg bid (LAC group, n = 228) in combination with amoxicillin 1 g bid and clarithromycin 500 mg bid. The patients received follow-up esophagogastroduodenoscopy (EGD) and/or C-13-urea breath test 12-16 weeks later to define H. pylori status. Their personal and medical history, compliance and side effects were obtained by using a standardized questionnaire. Intention-to-treat analysis revealed that the eradication rate was 87.84% in the RAC group and 85.96% in the LAC group (p = 0.56). All patients returned for assessment of compliance (100% in the LAC group vs. 99.50% in the RAC group; p = 0.32) and adverse events (7.20% in the RAC group vs. 5.70% in the LAC group, p = 0.51). Univariate analysis suggested that patients with nonsteroid anti-inflammatory agent (NSAID) use had lower eradication rates than those without (76.71% vs. 88.74%; p = 0.006). Our results showed that efficacy and safety were similar in rabeprazole-and lansoprazole-based primary therapies. The influence of NSAID usage on H. pylori eradication needs to be further investigated. Copyright (C) 2012, Kaohsiung Medical University. Published by Elsevier Taiwan LLC. All rights reserved.
Gastroesophageal reflux disease (GERD), a common disorder with troublesome symptoms caused by reflux of gastric contents into the esophagus, has adverse impact on quality of life. A variety of medications have been used in GERD treatment, and acid suppression therapy is the mainstay of treatment for GERD. Although proton pump inhibitor is the most potent acid suppressant and provides good efficacy in esophagitis healing and symptom relief, about one-third of patients with GERD still have persistent symptoms with poor response to standard dose PPI. Antacids, alginate, histamine type-2 receptor antagonists, and prokinetic agents are usually used as add-on therapy to PPI in clinical practice. Development of novel therapeutic agents has focused on the underlying mechanisms of GERD, such as transient lower esophageal sphincter relaxation, motility disorder, mucosal protection, and esophageal hypersensitivity. Newer formulations of PPI with faster and longer duration of action and potassium-competitive acid blocker, a newer acid suppressant, have also been investigated in clinical trials. In this review, we summarize the current and developing therapeutic agents for GERD treatment.
The current study was to investigate the interaction between Helicobacter pylori and human dendritic cells (DCs). Whether impaired DC function can influence the outcome of H. pylori infections. Human monocyte-derived DCs (MDDCs) from five gastric cancer patients and nine healthy controls were stimulated with H. pylori. Maturation markers of MDDC were examined by flow cytometry. IL-10 and TNF-α released by MDDCs and IL-17 produced by T cells were measured by ELISA. Regulatory signaling pathways of IL-10 were examined by ELISA, western blotting, and chromatin immunoprecipitation assay. The results showed that as compared with healthy individuals, the maturation marker CD40 in MDDCs, IL-17A expression from T cells, and IL-10 expression from MDDCs were significantly lower in gastric cancer patients. Blocking DC-SIGN, TLR2, and TLR4 could reverse H. pylori-associated IL-10 production. Activation of the p38 MAPK and NF-kB signaling pathways concomitant with decreased tri-methylated H3K9 and increased acetylated H3 accounted for the effect of H. pylori on IL-10 expression. Furthermore, upregulated IL-10 expression was significantly suppressed in H. pylori-pulsed MDDCs by histone acetyltransferase and methyltransferase inhibitors. Taken together, impaired DC function contributes to the less effective innate and adaptive immune responses against H. pylori seen in gastric cancer patients. H. pylori can regulate IL-10 production through Toll-like and DC-SIGN receptors, activates p-p38 MAPK signaling and the transcription factors NF-kB, and modulates histone modification.
Ichen Wu合作论文数Department of Computer Science and Information Engineering, National Chiao-Tung University7