Study of disease phenotype and its association with prognosis of paediatric inflammatory bowel disease in China.

BACKGROUND: To investigate the unique features of inflammatory bowel disease (IBD) in children, we wanted to identify whether there might be a strong correlation between the disease phenotype and its prognosis at various ages in paediatric patients. METHODS: We collected data from patients diagnosed with IBD (ulcerative colitis (UC) or Crohn's disease (CD)) from 2002 to 2016. The diagnosis was made according to the Porto criteria and Paris Classification. Patient characteristics, clinical manifestations and treatments were collected. Risk factors for surgery, mortality and relapse were analysed by Cox proportional hazard models. RESULTS: Of the 143 patients, 113 had CD, and 30 had UC; there were 89 males and 54 females with a median age of 9 years (y). Thirteen patients in the 0-2 y group were identified as having mutations in IL-10 receptor A, and this mutation was significantly more common in this age group than in 3-9 and 10-16 y patients. The risk factor for surgery was the B3 phenotype; risk factors for death were age 0-2 y and B3 phenotype; 0-2 y, B3 phenotype and steroid dependency were risk factors for early relapse. CONCLUSIONS: Clinical manifestations of the onset of IBD in infants and toddlers were extensive and aggressive and were closely associated with early relapse and death. It is of particular interest that some of these patients developed IBD due to monogenic disorders; thus, introduction of genetic testing is essential for these patients.

Role of the potassium chloride cotransporter isoform 2-mediated spinal chloride homeostasis in a rat model of visceral hypersensitivity.

Visceral hypersensitivity represents an important hallmark in the pathophysiology of irritable bowel syndrome (IBS), of which the mechanisms remain elusive. The present study was designed to examine whether cation-chloride cotransporter (CCC)-mediated chloride (Cl(-)) homeostasis of the spinal cord is involved in chronic stress-induced visceral hypersensitivity. Chronic visceral hypersensitivity was induced by exposing male Wistar rats to water avoidance stress (WAS). RT-PCR, Western blotting, and immunohistochemistry were used to assess the expression of CCCs in the spinal cord. Patch-clamp recordings were performed on adult spinal cord slices to evaluate Cl(-) homeostasis and Cl(-) extrusion capacity of lamina I neurons. Visceral sensitivity was estimated by measuring the abdominal withdrawal reflex in response to colorectal distension (CRD). After 10 days of WAS exposure, levels of both total protein and the oligomeric form of the K(+)-Cl(-) cotransporter isoform 2 (KCC2), but not Na(+)-K(+)-2Cl(-) transporter isoform 1 (NKCC1), were significantly decreased in the dorsal horn of the lumbosacral spinal cord. The downregulation of KCC2 resulted in a depolarizing shifted equilibrium potential of GABAergic inhibitory postsynaptic current and impaired Cl(-) extrusion capacity in lamina I neurons of the lumbosacral spinal cord from WAS rats. Acute noxious CRD disrupted spinal KCC2 expression and function 2 h after the final distention in sham rats, but not in WAS rats. Pharmacological blockade of KCC2 activity by intrathecal injection of a KCC2 inhibitor [(dihydroindenyl)oxy] alkanoic acid enhanced visceral nociceptive sensitivity in sham rats, but not in WAS rats. These results suggest that KCC2 downregulation-mediated impairment of spinal cord Cl(-) homeostasis may play an important role in chronic stress-induced visceral hypersensitivity.

Neuron-glial communication mediated by TNF-α and glial activation in dorsal root ganglia in visceral inflammatory hypersensitivity.

Communication between neurons and glia in the dorsal root ganglia (DRG) and the central nervous system is critical for nociception. Both glial activation and proinflammatory cytokine induction underlie this communication. We investigated whether satellite glial cell (SGC) and tumor necrosis factor-α (TNF-α) activation in DRG participates in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rat model of visceral hyperalgesia. In TNBS-treated rats, TNF-α expression increased in DRG and was colocalized to SGCs enveloping a given neuron. These SGCs were activated as visualized under electron microscopy: they had more elongated processes projecting into the connective tissue space and more gap junctions. When nerves attached to DRG (L6-S1) were stimulated with a series of electrical stimulations, TNF-α were released from DRG in TNBS-treated animals compared with controls. Using a current clamp, we noted that exogenous TNF-α (2.5 ng/ml) increased DRG neuron activity, and visceral pain behavioral responses were reversed by intrathecal administration of anti-TNF-α (10 µg·kg(-1)·day(-1)). Based on our findings, TNF-α and SGC activation in neuron-glial communication are critical in inflammatory visceral hyperalgesia.

Resolution of new-onset diabetes after radical pancreatic resection predicts long-term survival in patients with pancreatic ductal cell adenocarcinoma.

PURPOSE: To demonstrate the effect of diabetes mellitus (DM) (stratified by long-term/new-onset presurgical diabetes, resolved/unresolved postsurgical diabetes) on prognosis for pancreatic ductal cell adenocarcinoma (PDAC) after radical resection. METHODS: One hundred ninety-nine patients who underwent radical resection for PDAC between 2007 and 2011 at Ruijin Hospital (Shanghai, China) were retrospectively analyzed. Clinical and pathologic characteristics, surgical and adjuvant chemotherapy related outcomes, disease-free survival (DFS), and postoperative survival were compared among patients with long-term (≥2 years)/new-onset (<2 years) presurgical diabetes and resolved/unresolved postsurgical diabetes. Univariate and multivariable analysis was performed to determine factors associated with DFS and overall survival (OS). RESULTS: Of 199 patients, 90 (44.7%) had DM, 64 of which were new onset and 26 of which were long-standing. Resolution of DM after radical pancreatic resection was observed in 65% (42 of 64) in the new-onset group, but in none of the long-standing group. Resolved new-onset DM patients had larger, well-differentiated tumors compared to patients with unresolved new-onset DM. Patients with long-standing DM had shorter postoperative DFS and OS than nondiabetic/new-onset DM, whereas postoperative resolved new-onset DM is associated with longer DFS and OS than unresolved DM. Morbidity was higher and postoperative hospital stay was longer in patients with new-onset DM compared with patients with long-standing DM and patients without DM. There was no difference in the adjuvant chemotherapy toxicity rate among patients with long-standing or new-onset DM and those without DM. CONCLUSIONS: Different status of DM has different effects on outcome after resection for PDAC. Long-standing DM is related to progression of disease, whereas postsurgical resolved new-onset DM is a favorable prognostic factor.

Direct visualization of drug behaviors in the upper GI tract via magnetically controlled capsule endoscopy.

BACKGROUND AND AIMS: Actual behaviors of drugs in the upper GI tract are not well elucidated. We assess the feasibility of magnetically controlled capsule endoscopy (MCE) in direct and real-time visualization of oral drug behaviors in the stomach. METHODS: From November 2019 to December 2019, 9 patients with a recent history of upper GI symptoms and 10 healthy volunteers were enrolled in this study. Participants swallowed magnetically controlled capsules to examine the whole stomach. After baseline examination, participants ingested dyed sucralfate gel, and MCE recorded the adhesion time, retention time, and distribution area of sucralfate gel. Outcomes included behaviors of sucralfate gel, safety, and satisfaction assessment of the procedures. RESULTS: Adhesion time of sucralfate gel in the abdominal symptoms group was significantly shorter than in the healthy control group (23.76 ± 1.37 minutes vs 31.96 ± 3.09 minutes; P = .032), whereas retention time was longer (98.85 ± 13.94 minutes vs 63.93 ± 8.57 minutes; P = .043). The distribution area of sucralfate gel in the abdominal symptoms group was significantly larger than in healthy control group in cardia (24.29 ± 7.39 vs 9.18 ± 4.06; P < .0001), fundus (18.90 ± 7.08 vs 8.49 ± 4.10; P = .0015), and pylorus (4.64 ± 2.72 vs 0.94 ± 0.90; P = .0019). No adverse events were observed. All participants had a high degree of satisfaction. CONCLUSIONS: MCE is a feasible and noninvasive tool for direct and real-time visualization of drug behaviors (eg, sucralfate gel) in the stomach. (ClinicalTrials.gov. ID: NCT04327869.).

XAF1 as a prognostic biomarker and therapeutic target in pancreatic cancer.

XAF1 (X chromosome-linked inhibitor of apoptosis [XIAP]-associated factor 1) is a novel XIAP modulator that negatively regulates the anti-apoptotic effects of XIAP and sensitizes cells to other cell death triggers. It has been reported to be downregulated in a variety of human cancer cell lines. However, the role of XAF1 in pancreatic carcinogenesis remains unclear. In the present study, we investigated the prognostic values of XAF1 expression and its regulation in cancer cell growth and apoptosis both in vitro and in vivo. From the immunohistochemistry staining of tissue microarray, 40 of 89 (44.9%) pancreatic specimens showed low levels of XAF1 expression. Statistical analysis suggested the downregulation of XAF1 was significantly correlated with tumor staging (P = 0.047) and those patients with low XAF1 levels had shorter survival times (P = 0.0162). Multivariate analysis indicated that XAF1 expression was an independent prognostic indicator of the survival of patients with pancreatic cancer (P = 0.007). Furthermore, we found that restoration of XAF1 expression mediated by Ad5/F35 virus suppressed cell proliferation and induced cell cycle arrest and apoptosis, accompanied by the activation of caspases 3, 8, and 9 and poly(ADP-ribose) polymerase as well as increased level of cytochrome c and Bid cleavage. Notably, XAF1 restoration robustly decreased survivin expression rather than XIAP. In addition, in vivo s.c. xenografts from Ad5/F35-XAF1 treatment, which showed less cellular proliferation and enhanced apoptosis, were significantly smaller than those from control groups. Our findings document that XAF1 is a valuable prognostic marker in pancreatic cancer and could be a potential candidate for cancer gene therapy.

Positive expression of L1-CAM is associated with perineural invasion and poor outcome in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) frequently invades and migrates along neural tissue, which results in local tumor recurrences, distant metastases, and poor prognosis. We evaluated whether L1 cell adhesion molecule (L1-CAM) and glial cell line-derived neurotrophic factor (GDNF) expression in PDAC correlated with neural invasion and overall survival on a large cohort of previously untreated patients. METHODS: L1-CAM and GDNF were examined by immunohistochemistry in pancreatic cancer tissue samples of 94 cases with PDAC on a tissue microarray. The molecular findings were correlated with pain, clinicopathologic characteristics, and overall survival in these patients. RESULTS: L1-CAM and GDNF were overexpressed in pancreatic cancer tissues compared with the adjacent normal tissues of pancreas. Positive L1-CAM expression was associated with node involvement (P = 0.007), vascular invasion (P = 0.012), perineural invasion (P = 0.001), and higher degree of pain (P = 0.005). In univariate analysis, tissue expression of L1-CAM was associated with poor survival (hazard ratio, 2.508; 95% confidence interval, 1.551-4.053; P < 0.001), and this was also significant in multivariate analysis (hazard ratio, 2.046; 95% confidence interval, 1.200-3.488; P = 0.009). Positive staining of GDNF, neural invasion, and vascular invasion were all statistically significantly related to unfavorable prognosis. CONCLUSIONS: Enhanced expression of L1-CAM may contribute to the pain syndrome and perineural invasion and may correlate with poor overall survival in human pancreatic cancer.

[Evaluation of the effect of ilaprazole on intragastric pH in patients with duodenal ulcer].

OBJECTIVE: To evaluate the effect of ilaprazole enteric tablets on intragastric pH in duodenal ulcer patients. METHODS: A randomized, double blind, positive controlled clinical trial was carried out. A total of forty-two patients with duodenal ulcer were randomized into low dose ilaprazole group (5 mg/d), medium dose ilaprazole group (10 mg/d), high dose ilaprazole group (20 mg/d) and omeprazole group (20 mg/d). An ambulatory 24 hour intragastric pH study was performed at the fifth treatment day. Fraction time pH above 3, 4 or 5, median values of 24 hour diurnal pH and 12 hour nocturnal pH, the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours were evaluated. RESULTS: There were no significant differences of fraction time pH above 3 or 4, median values of 24 hour diurnal pH and 12 hour nocturnal pH and the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours among all the groups with different doses of ilaprazole and the omeprazole group. The fraction time pH above 5 in medium and high dose ilaprazole groups were (87.96 + or - 12.29)% and (89.86 + or - 15.18)% respectively, which was higher than that in low dose ilaprazole group [(67.17 + or - 30.16)%] and omeprazole group [(76.14 + or - 16.75)%], P < 0.05. CONCLUSION: Ilaprazole has a strong effect on intragastric acid control with a dose dependent trend.

Voltage-gated potassium channels in IB4-positive colonic sensory neurons mediate visceral hypersensitivity in the rat.

OBJECTIVES: Irritable bowel syndrome (IBS) is associated with a state of chronic visceral hypersensitivity, but the underlying molecular mechanisms of visceral hyperalgesia remain elusive. This study was designed to examine changes in the excitability and alterations of voltage-gated K+ currents in subpopulations of colonic dorsal root ganglion (DRG) neurons in a rat model of IBS-like visceral hypersensitivity. METHODS: The model of IBS-like visceral hypersensitivity was induced by intracolonic infusion of 0.5% acetic acid (AA) in saline from postnatal days 8 -21. Experiments were conducted when rats became adults. DRG neurons innervating the colon were identified by 1,1'-dioleoyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate (DiI) fluorescence labeling and were immunostained for isolectin B4 (IB4) binding to classify these colonic neurons. Patch-clamp recordings were made from acutely dissociated DiI-labeled DRG neurons, and the expression of K+ channel in L6-S2 DRG was examined by reverse transcription-polymerase chain reaction (RT-PCR) and western blot. RESULTS: (1) Neonatal AA treatment induced long-lasting visceral hypersensitivity without significant inflammation but with mast cell hyperplasia. (2) Colonic DRG neurons contained IB4-positive and negative neurons with different electrophysiological properties. IB4-positive colonic neurons have longer action potentials (APs) and larger A-type K+ currents (I(A)) than the IB4-negative neurons, and IB4 phenotypic changes of colonic neurons were not involved in the chronic visceral hypersensitivity. (3) Neonatal AA treatment decreased I(A) density and changed the electrophysiological properties of I(A) and I(K) by shifting the steady-state inactivation toward a negative direction in IB4-positive colonic neurons. The excitability of these cells increased. (4) Kv4.3 was downregulated in neonatal AA-treated rats compared with control rats, which suggests a possible mechanism regarding the changes in electrical activity of DRG neurons in these rats. CONCLUSIONS: A new model for chronic visceral hypersensitivity following a diluted AA stimulus in the neonatal period is described. The hypersensitivity may be associated with mast cell hyperplasia in the colon and increased excitability of IB4-positive colonic neurons as a result of suppression of I(A) density and a shift in the inactivation curves of I(A) and I(K) in a hyperpolarizing direction in these cells. This study identifies for the first time a specific molecular mechanism in subpopulations of colonic DRG neurons that underlies chronic visceral hypersensitivity.

Circulating levels of periostin may help identify patients with more aggressive colorectal cancer.

Elevated levels of periostin have been implicated as playing important roles in tumor invasion and metastasis in various tissues. Thus, we determined whether serum periostin levels were associated with progression and poor prognosis in colorectal cancer (CRC) patients. We measured serum periostin levels by ELISA in 67 CRC patients and 120 controls. We also evaluated periostin expression in human CRC specimens (n=15) using immunohistochemistry, and measured expression of periostin mRNA in 7 CRC tissue samples, matched normal tissues and in 4 colon cancer cell lines by RT-PCR. We analyzed the relationship between serum levels of periostin and other clinicopathologic characteristics in patients with CRC. The serum levels of periostin in CRC patients (40.9+/-15.4 ng/ml) were significantly elevated compared to that in healthy volunteers (21.0+/-7.3 ng/ml, P<0.0001) and benign colorectal polyps or adenomas (22.4+/-8.5 ng/ml, P<0.0001). Higher preoperative serum levels of periostin in CRC were found to correlate with distant metastasis (P=0.003), advanced-stage disease (stage III/IV, P<0.0001) and poor prognosis. Preoperative serum periostin levels of 15 cases were significantly higher than matched postoperative levels (47.2+/-13.5 ng/ml vs. 31.3+/-11.0 ng/ml, P=0.008). Twelve of 15 patients (80%) had positive immunohistochemical periostin staining in CRC samples. Interestingly, periostin mRNA was highly upregulated in CRCs in comparison with matched normal tissues, and no expression of periostin mRNA was detected in 4 colon cancer cell lines. Serum levels of periostin detected by ELISA may be of clinical value in identifying patients who may be at high risk for aggression and metastasis of CRC. Periostin may be produced by the stromal cells surrounding the tumor, but not by the CRC cells themselves.

[Long-term impact on quality of life in patients with gastroesophageal reflux disease after 52-week rabeprazole treatment].

OBJECTIVE: To investigate the longitudinal changes in quality of life (QoL) for gastroesophageal reflux disease (GERD) treated with 52-week rabeprazole over a period of 2-3 years. METHODS: A multi-center, open-label and randomized 52-week rabeprazole trial was conducted in 67 eosinophilic esophagitis (EE) and 31 non-erosive reflux disease (NERD) patients. The follow-up period is 2-3 years after the treatment. Their QoL were evaluated using SF-36 Health Survey Questionnaire and GERD-HRQL scale. The results were compared with those acquired before and after a 52-week proton pump inhibitor (PPI) treatment. RESULTS: (1) Both EE and NERD patients improved significantly according to GERD-HRQL scale in scores of reflux symptoms as well as overall satisfaction (12.5 vs 3.5, 20.0 vs 14.0, both P < 0.01) versus the pre-therapy baseline. (2) Both EE and NERD patients had no significant difference in the scale of GERD-HRQL (2.0 vs 3.5, 5.0 vs 4.0, both P > 0.05) and most major domains of SF-36 questionnaire versus the post-therapy baseline (53 +/- 17 vs 61 +/- 17, t = -2.143, P = 0.035). (3) The NERD patients had a higher score of reflux symptoms than the EE patients according to the GERD-HRQL Scale (14.0 vs 3.5, Z = 2.377, P = 0.017), however there were no significant differences between NERD and EE in 8 major domains of SF-36 questionnaire (P > 0.05). CONCLUSION: Long-term and low-dose PPI treatment achieves improvement both in reflux symptoms and QoL in GERD patients and such effects last a long time. At follow-ups, the reflux symptoms of NERD patients are more severe than EE patients. However, the overall QoL has shown little differences between these two subtypes.

Cigarette Smoking and Mortality in Patients With Pancreatic Cancer: A Systematic Review and Meta-analysis.

Current evidence on cigarette smoking associated with pancreatic cancer mortality is limited. We searched MEDLINE, Web of Science, and Embase databases to identify relevant studies published through January 31, 2018. A random-effects model was used to estimate summary hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 20 studies were retrieved, involving 2,517,623 participants. Of these, more than 15,341 patients with pancreatic cancer died. Compared with never smokers, current (summary HR, 1.56; 95% CI, 1.34-1.83) and former (summary HR, 1.15; 95% CI, 1.06-1.26) smokers had elevated risk of total mortality in patients diagnosed with pancreatic cancer. This effect of cigarette smoking is observed both in the Western regions and the Asia-Pacific regions. This effect of smoking is independent of alcohol use, body mass index, and history of diabetes but is modified by tumor stage and study settings. Dose-response associations between smoking and pancreatic cancer mortality were revealed for smoking intensity, cumulative amount of cigarettes smoked, and duration of smoking. Cigarette smoking was associated with an increase in total mortality for patients with pancreatic cancer. Future studies should further clarify the role of smoking as an effect modifier in treatment trials of pancreatic cancer.

A randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of tegaserod in patients from China with chronic constipation.

AIM: To evaluate the efficacy and safety of tegaserod, 6 mg twice daily (b.i.d.), in men and women with chronic constipation (CC) from China. METHODS: This was a multicenter, double-blind, placebo-controlled study. Following a 2-wk treatment-free baseline period, patients were randomized to receive either tegaserod (6 mg b.i.d.) or placebo (b.i.d.) for 4 wk. An analysis of covariance with repeated measures was used to determine the overall effect of treatment for the primary efficacy variable; the change from baseline in the number of complete spontaneous bowel movements (CSBMs) during the 4-wk treatment period. Secondary efficacy endpoints included other measures of response in terms of CSBMs, and patients' daily and weekly assessment of bowel habits. Safety was also assessed, based on the incidence and severity of adverse events (AEs). RESULTS: A total of 607 patients were randomized to receive either tegaserod (n = 304) or placebo (n = 303). Tegaserod treatment resulted in a rapid and significant increase from baseline in the adjusted mean number of CSBMs per week over wk 1-4 compared with placebo (1.39 vs 0.91, P = 0.0002). A statistically significant difference in favor of tegaserod was also observed for a mean increase > or = 1 CSBM/wk over wk 1-4 (47.7% vs 35.0%, tegaserod vs placebo, respectively, P = 0.0018) and for the absolute number of > or = 3 CSBMs/wk over wk 1-4 (25.0% vs 14.5%, tegaserod vs placebo, respectively, P = 0.0021). Improvements in other symptoms of CC were also seen in the tegaserod group, including improved stool form and reduced straining. In addition, more patients in the tegaserod group reported satisfactory relief from their constipation symptoms. The frequency and severity of AEs was comparable between tegaserod and placebo groups, with the exception of a greater incidence of diarrhea in patients receiving tegaserod (3.6%) compared with placebo (1.7%). CONCLUSION: Tegaserod treatment improved multiple symptoms of CC and was associated with a favorable safety profile.

Comparison of Prevention of NSAID-Induced Gastrointestinal Complications by Rebamipide and Misoprostol: A Randomized, Multicenter, Controlled Trial-STORM STUDY.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects such as dyspepsia, peptic ulcer, hemorrhage, and perforation. Misoprostol and PPIs have been used to prevent NSAID-induced gastroduodenal injury. Rebamipide increases gastric mucus and stimulates the production of endogenous prostaglandins. The prophylactic effect of rebamipide on NSAID-induced gastrointestinal complications is unknown. The aim of this study was to compare NSAID-induced gastrointestinal complications in rebamipide- and misoprostol-treated groups. Patients were randomized to two groups and took a conventional NSAID plus rebamipide or misoprostol for 12 weeks. Gastric mucosal damage was evaluated by endoscopy at screening and the end of the study. The prevalences of active gastric ulcer were 7/176 (3.9%) in the rebamipide group and 3/156 (1.9%) in the misoprostol group. The prevalences of peptic ulcer were 8/176 (4.5%) in the rebamipide group and 7/156 (4.4%) in the misoprostol group. The cumulative incidences of peptic ulcer in the high-risk subgroup were 6/151 (4.0%) for rebamipide and 6/154 (3.9%) for misoprostol. In conclusion, rebamipide prevented NSAID-induced peptic ulcer as effectively as misoprostol in patients on long-term NSAID therapy. Rebamipide may be a useful therapeutic option for the prevention of NSAID-induced gastrointestinal ulcer because of its therapeutic effect and safety.

Adsorptive Granulocyte and Monocyte Apheresis in the Treatment of Ulcerative Colitis: The First Multicenter Study in China.

BACKGROUND/AIMS: Patients with active ulcerative colitis (UC) have elevated levels of activated myeloid-derived leukocytes as a source of inflammatory cytokines. The selective depletion of these leukocytes by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn should alleviate inflammation, promote remission and enhance drug efficacy. However, studies have reported contrasting efficacy outcomes based on patients' baseline demographic variables. This study was undertaken to understand the demographic features of GMA responders and nonresponders. METHODS: This was a multicenter study in China involving four institutions and 34 patients with active UC. Baseline conventional medications were continued without changing the dosage. The treatment efficacy was evaluated based on the endoscopic activity index and the Mayo score. RESULTS: Thirty of the 34 patients completed all 10 GMA treatment sessions. The overall efficacy rate was 70.59%. The receiver operating characteristic analysis showed that the area under the curve was approximately 0.766 for a Mayo score of ≤5.5 with 0.273 specificity and 0.857 sensitivity (Youden index, 0.584) for GMA responders. No GMA-related serious adverse events were observed. CONCLUSIONS: The overall efficacy of GMA in patients with active UC who were taking first-line medications or were corticosteroid refractory was encouraging. Additionally, GMA was well tolerated and had a good safety profile.

Alginate antacid (Gaviscon DA) chewable tablets reduce esophageal acid exposure in Chinese patients with gastroesophageal reflux disease and heartburn symptoms.

OBJECTIVE: To assess the efficacy of Gaviscon Double Action (DA) alginate antacid chewable tablets for reducing esophageal acid exposure in Chinese patients with gastroesophageal reflux disease (GERD). METHODS: Altogether 44 patients reporting moderate to severe heartburn symptoms underwent two pH monitoring visits. The treatment sequence was randomized to patients received DA alginate antacid or placebo at one visit and the alternate treatment 7 days later. After a standardized reflux-provoking meal, patients took four tablets of DA alginate antacid or placebo. Esophageal pH was measured for 4 h post-dosing using an electrode positioned 5 cm above the lower esophageal sphincter. The primary end-point was the percentage of 4-h post-dosing period with pH <4. Secondary end-points were number of acid reflux episodes (pH <4), longest reflux time and DeMeester scores. RESULTS: All 44 patients completed the study and provided data for analysis. With DA alginate antacid, the mean percentage time with pH <4 was 5.1%, significantly less (P = 0.0003) than with placebo (14.8%). DA alginate antacid was statistically significantly superior (P = 0.0290) to placebo (from at least twofold to threefold better) for all other end-points. Two patients reported two mild adverse events (AEs) that resolved within a month of completing the study. No patients had serious and/or severe AEs and none withdrew due to AEs. CONCLUSIONS: DA alginate antacid was statistically significantly superior to placebo in reducing post-prandial acid exposure without serious clinically relevant health risks. These findings suggest DA alginate antacid tablets are appropriate for treating acid reflux in Chinese GERD patients with heartburn symptoms.

Differences and Similarities in the Clinicopathological Features of Pancreatic Neuroendocrine Tumors in China and the United States: A Multicenter Study.

The presentation, pathology, and prognosis of pancreatic neuroendocrine tumors (PNETs) in Asian patients have not been studied in large cohorts. We hypothesized that the clinicopathological features of PNETs of Chinese patients might be different from those of US patients. The objectives of this study were to address whether PNETs in Chinese patients exhibit unique clinicopathological features and natural history, and can be graded and staged using the WHO/ENETS criteria. This is a retrospective review of medical records of patients with PNETs in multiple academic medical centers in China (7) and the United States (2). Tumor grading and staging were based on WHO/ENETS criteria. The clinicopathological features of PNETs of Chinese and US patients were compared. Univariate and multivariate analyses were performed to find associations between survival and patient demographics, tumor grade and stage, and other clinicopathological characteristics. A total of 977 (527 Chinese and 450 US) patients with PNETs were studied. In general, Chinese patients were younger than US patients (median age 46 vs 56 years). In Chinese patients, insulinomas were the most common (52.2%), followed by nonfunctional tumors (39.7%), whereas the order was reversed in US patients. Tumor grade distribution was similar in the 2 countries (G1: 57.5% vs 55.0%; G2: 38.5% vs 41.3%; and G3: 4.0% vs 3.7%). However, age, primary tumor size, primary tumor location, grade, and stage of subtypes of PNETs were significantly different between the 2 countries. The Chinese nonfunctional tumors were significantly larger than US ones (median size 4 vs 3 cm) and more frequently located in the head/neck region (54.9% vs 34.8%). The Chinese and US insulinomas were similar in size (median 1.5 cm) but the Chinese insulinomas relatively more frequently located in the head/neck region (48.3% vs 26.1%). Higher grade, advanced stage, metastasis, and larger primary tumor size were significantly associated with unfavorable survival in both countries. Several clinicopathological differences are found between Chinese and US PNETs but the PNETs of both countries follow a similar natural history. The WHO tumor grading and ENETS staging criteria are applicable to both Chinese and US patients.

[The impact of rabeprazole treatment on the quality of life in patients with reflux esophagitis and non-erosive reflux disease].

OBJECTIVE: To compare the health-related quality of life (HRQL) in the patients with reflux esophagitis (RE) and non-erosive reflux disease (NERD) treated with rabeprazole in the multi-center open study. METHODS: All patients were treated with rebaprazole (10 mg, bid, ac) for eight weeks from Dec. 2002 to June 2003. 74 patients with RE; and 37 patients with NERD defined as negative endoscopic finding, the Demeester scores of 24 h pH monitoring of esophagus > 14.27 and reflux symptoms score > 6, were enrolled in. The impacts on HRQL (SF-36 questionnaire) and GERD-HRQL were assessed before and after therapy. RESULTS: At baseline, HRQL in NERD patients was impaired greater than in RE patients. After therapy, the symptoms were improved significantly in both groups. The quality of life was improved in 7 subscales in RE patients. However it was much lower in NERD patients. The scale of GERD-HRQL decreased significantly in RE patients than in NERD patients. CONCLUSIONS: NERD causes a more significant impairment in the quality of life than RE, which can be attenuated partly after 8 w rabeprazole therapy, unlike the satisfactory results favored in RE. Further research is needed to more completely understand the value of rabeprazole therapy for NERD.

[Effect of changji' an oral liquid on activated signal alterative intensity in algesthesia domain in patients with diarrhea type irritable bowel syndrome due to gan-pi disharmony].

OBJECTIVE: To observe the effect of Changji' an (CJA) oral liquid on the activated signal alterative intensity (ASAI) in intracranial algesthesia domain in patients with diarrhea type irritable bowel syndrome (IBS) due to Gan-Pi disharmony. METHODS: Twenty-four patients were randomly divided into 2 groups, 14 in the treated group and 10 in the control group, they were administrated with CJA and placebo respectively. The sensory threshold and score in the two groups recorded by rectal inflation test were compared and analyzed. The change of ASAI in intracranial algesthesia domain was analyzed by functional magnetic resonance imagine (fM-RI) during rectum being inflated with 30 ml, 60 ml, 90 ml and 120 ml of gas respectively. RESULTS: The initial sensory thresholds in the two groups were insignificantly different, but significant difference did show between the two groups in urgent defecation threshold and pain threshold after treatment (P < 0.05). Comparison in visual simulative scores between the two groups after treatment at rectal inflated for 30 ml showed no significant difference, but it showed significant difference when the inflation was over 30 ml (P < 0.05). In the treated group, the ASAI in insula cortex when rectal inflation being 90 ml or 120 ml and that in thalamus when rectal inflation being 120 ml were significantly decreased (P < 0.05). But in the control group, it changed insignificantly after treatment. CONCLUSION: The treatment of CJA on Gan-Pi disharmony caused diarrhea type IBS might be effected by regulating the ASAI in intracranial insula cortex and thalamus.