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Background: Neurokinin-1 receptor antagonists are playing a major advance in Chemotherapy-Induced Nausea and Vomiting (CINV) as powerful prophylactic agents. Therefore, it is significant to find the association between risk factors of patients and CINV so as to adjust the anti-emetic regimens. Objective: To evaluate the role of Neurokinin-1 Receptor (NK-1R) antagonist in preventing chemotherapy-induced vomiting in the acute and delayed phases following the first cycle of treatment. Methods: 145 adult patients with various cancers were recruited in Shanghai Changhai Hospital between September 2017 to November 2017, receiving dual or triple antiemetics. Results: NK-1R antagonist combined with dexamethasone, 5-HT3R antagonist could effectively control delayed- vomiting in patients after Cycle 1 chemotherapy treatment (4.1% vs. 15.6%, P = 0.041 Conclusion: In this study, we found that triple anti-emetic regimen with NK-1R antagonist could effectively prevent the delayed-vomiting than dual agents. Moreover, some risk factors were observed to be associated with CINV in the delayed phase.

Replacement of the exocrine parenchyma by fibrous tissue is a main characteristic of chronic pancreatitis. Understanding the mechanisms of pancreatic fibrogenesis is critical for the development of preventive and therapeutic interventions. Cyclooxygenase-2 (COX-2), a rate-limiting enzyme for prostaglandin synthesis, is expressed in patients with chronic pancreatitis. However, it is unknown whether COX-2 can cause chronic pancreatitis. To investigate the roles of pancreatic acinar COX-2 in fibrogenesis and the development of chronic pancreatitis, COX-2 was ectopically expressed specifically in pancreatic acinar cells in transgenic mice. Histopathological changes and expression levels of several profibrogenic factors related to chronic pancreatitis were evaluated. COX-2 was expressed in the pancreas of the transgenic mice, as detected by Western blot analysis. Immunohistochemical staining showed COX-2 was specifically expressed in pancreatic acinar cells. COX-2 expression led to progressive changes in the pancreas, including pancreas megaly, persistent inflammation, collagen deposition, and acinar-to-ductal metaplasia. Quantitative RT-PCR and immunostaining showed that profibrogenic factors were upregulated and pancreatic stellate cells were activated in the COX-2 transgenic mice. Expression of COX-2 in pancreatic acinar cells is sufficient to induce chronic pancreatitis. Targeting this pathway may be valuable in the prevention of chronic pancreatitis. NEW & NOTEWORTHY COX-2 expression is observed in pancreatic tissues of human chronic pancreatitis. In this study, we showed that COX-2 expression caused the development of chronic pancreatitis in transgenic mice, supporting the idea that COX-2 inhibition may be an effective preventive and therapeutic strategy.

Intra-acinar trypsinogen activation occurs in the earliest stages of pancreatitis and is believed to play important roles in pancreatitis pathogenesis. However, the exact role of intra-acinar trypsin activity in pancreatitis remains elusive. Here, we aimed to examine the specific effects of intra-acinar trypsin activity on the development of pancreatitis using a transgenic mouse model. This transgenic mouse model allowed for the conditional expression of a mutant trypsinogen that can be activated specifically inside pancreatic acinar cells. We found that expression of this active mutated trypsin had no significant effect on triggering spontaneous pancreatitis. Instead, several protective compensatory mechanisms, including SPINK1 and heat shock proteins, were upregulated. Notably, these transgenic mice developed much more severe acute pancreatitis, compared with control mice, when challenged with caerulein. Elevated tissue edema, serum amylase, inflammatory cell infiltration and acinar cell apoptosis were dramatically associated with increased trypsin activity. Furthermore, chronic pathological changes were observed in the pancreas of all transgenic mice, including inflammatory cell infiltration, parenchymal atrophy and cell loss, fibrosis, and fatty replacement. These changes were not observed in control mice treated with caerulein. The alterations in pancreata from transgenic mice mimicked the histological changes common to human chronic pancreatitis. Taken together, we provided in vivo evidence that increased intra-acinar activation of trypsinogen plays an important role in the initiation and progression of both acute and chronic pancreatitis. NEW & NOTEWORTHY Trypsinogen is activated early in pancreatitis. However, the roles of trypsin in the development of pancreatitis have not been fully addressed. Using a genetic approach, we showed trypsin activity is critical for the severity of both acute and chronic pancreatitis.

Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere.

Background & Aims Mutations in the trypsinogen gene (PRSS1) cause human hereditary pancreatitis. However, it is not clear how mutant forms of PRSS1 contribute to disease development. We studied the effects of expressing mutant forms of human PRSS1 in mice. Methods We expressed forms of PRSS1 with and without the mutation encoding R122H (PRSS1R122H) specifically in pancreatic acinar cells under control of a full-length pancreatic elastase gene promoter. Mice that did not express these transgenes were used as controls. Mice were given injections of caerulein to induce acute pancreatitis or injections of lipopolysaccharide to induce chronic pancreatitis. Other groups of mice were fed ethanol or placed on a high-fat diet to induce pancreatitis. Pancreata were collected and analyzed by histology, immunoblots, real-time polymerase chain reaction, and immunohistochemistry. Trypsin enzymatic activity and chymotrypsin enzymatic activity were measured in pancreatic homogenates. Blood was collected and serum amylase activity was measured. Results Pancreata from mice expressing transgenes encoding PRSS1 or PRSS1R122H had focal areas of inflammation; these lesions were more prominent in mice that express PRSS1R122H. Pancreata from mice that express PRSS1 or PRSS1R122H had increased levels of heat shock protein 70 and nuclear factor (erythroid-derived 2)–like 2, and reduced levels of chymotrypsin C compared with control mice. Increased expression of PRSS1 or PRSS1R122H increased focal damage in pancreatic tissues and increased the severity of acute pancreatitis after caerulein injection. Administration of lipopolysaccharide exacerbated inflammation in mice that express PRSS1R122H compared to mice that express PRSS1 or control mice. Mice that express PRSS1R122H developed more severe pancreatitis after ethanol feeding or a high-fat diet than mice that express PRSS1 or control mice. Pancreata from mice that express PRSS1R122H had more DNA damage, apoptosis, and collagen deposition and increased trypsin activity and infiltration by inflammatory cells than mice that express PRSS1 or control mice. Conclusions Expression of a transgene encoding PRSS1R122H in mice promoted inflammation and increased the severity of pancreatitis compared with mice that express PRSS1 or control mice. These mice might be used as a model for human hereditary pancreatitis and can be studied to determine mechanisms of induction of pancreatitis by lipopolysaccharide, ethanol, or a high-fat diet.

Objective We aimed to identify the risk factors for predicting pancreatic infection in patients with severe acute pancreatitis (SAP). Methods In all, 163 patients with SAP were included and divided into two groups based on the presence or absence of pancreatic infection. Their demographic and clinical characteristics, laboratory examination results, complications and treatment modalities were collected from their medical records. Variables were initially screened by univariate analysis and those with statistical significance were then filtered by multivariate analysis to determine the independent risk factors for pancreatic infection in SAP. Results Patients having SAP with pancreatic infection had a lower partial pressure of arterial carbon dioxide (PaCO2), peripheral white blood cell count and alkaline phosphatase levels, together with a higher computed tomography severity index (CTSI) than those without pancreatic infection, while their lactate dehydrogenase (LDH) levels and blood urea nitrogen were much higher. Pancreatic infection was also more common in patients receiving late fluid resuscitation than in those receiving early fluid resuscitation. Multivariate analyses revealed that increased LDH level, high CTSI, delayed fluid resuscitation and hypoxemia were independent risk factors for pancreatic infection in SAP. The sensitivity, specificity, positive and negative predictive values for a model combining the parameters in predicting pancreatic infection were 84%, 97%, 88% and 96%, respectively, with a cut-off value of 0.393, and the area under the receiver operating characteristic curve was 0.923. Conclusion Increased LDH, high CTSI, delayed fluid resuscitation and hypoxemia are independent risk factors for predicting pancreatic infection in patients with SAP.

Aims. We attempted to establish some guidelines for the selection of transmural stents during endoscopic drainage of PFCs by retrospective review of the clinical data obtained from three tertiary hospitals.Patients and Methods. Clinical data of 93 patients with attempted endoscopic drainage of symptomatic PFCs were obtained through chart review and prospective follow-up.Results. Treatment success for acute pseudocyst (n=67), chronic pseudocyst (n=9), and WOPN (n=17) was 95.3%, 100%, and 88.2%, respectively (P=0.309). Clinical success for single-stent drainage was 93.9% (46/49) versus 97.4% (37/38) for multiple-stent drainage (P=0.799). Secondary infection for single-stent drainage was 18.4% (9/49) versus 5.3% (2/38) for multiple-stent drainage (P=0.134). Secondary infection for stent diameter less than or equal to 8.5 F was 3.4% (1/29) versus 17.2% (10/58) for stent diameter larger than or equal to 10 F (P=0.138).Conclusion. EUS-guided transmural drainage is an effective therapy for PFCs. Single-stent transmural drainage of PFCs is enough and does not seem to influence clinical success. The number or diameter of stents does not seem to be associated with secondary infection.

ObjectiveWe aimed to describe the clinical picture, management and outcomes of Chinese patients with peptic ulcer bleeding (PUB), especially in those with high risks. MethodsA multicenter endoscopic survey was conducted. All consecutive patients with endoscopy confirmed PUB from October 2010 to June 2011 were enrolled. Data including patients' gender, age, symptoms and endoscopic findings, Forrest classification, and endoscopic and medical treatment were documented. High-risk ulcer was defined as Forrest grades Ia to IIb upon endoscopy. Rates of rebleeding, surgery and mortality were recorded. ResultsIn all, 1006 patients were included. Of these 437 (43.4%) were categorized with high-risk PUB, among whom 110 (25.2%) received endoscopic treatment, and the success rate was 99.1%. Rebleeding rates 1-3 days, 4-5 days and 6-30 days after treatment in high-risk patients who did and did not receive endoscopic treatment were 10.9% versus 10.4%, 3.6% versus 3.7% and 0.9% versus 1.5%, respectively. The surgery rates of high-risk patients with or without endoscopic treatment were 1.8% (2/110) versus 1.8% (6/327). During the 9-month study period, two patients with high-risk PUB died, therefore, the overall mortality rate of high-risk PUB was 0.5% (2/437). ConclusionThe study suggests that the proportions of high-risk PUB in China is 43.4%, while rebleeding and surgery rate after endoscopic treatment as well as the mortality rate of high-risk PUB in China are 15.6%, 1.8% and 0.5%, respectively.

The transpapillary approach can be used for draining pancreatic pseudocysts (PPs) with pancreatic-duct abnormalities. The purpose of this study was to analyze prognostic factors for clinical success of transpapillary drainage. Data for all patients who underwent transpapillary drainage between November 2000 and September 2009 were obtained by retrospective review and entered into a computerized database. Patient data were prospectively followed up to determine long-term outcomes. Seventy interventional ERCP procedures were performed for 43 patients. Technical success was 90.7 % (39/43). Overall clinical success was 79.5 % (31/39). Clinical success for pancreatic head pseudocyst was significantly different from that for body or tail pseudocyst (62.5 vs. 91.3 %, P = 0.043). Logistic regression analysis showed that location of the PPs predicted the success of endoscopic transpapillary pseudocyst drainage (P = 0.025). Transpapillary drainage is the least traumatic approach for drainage of PPs, and is also effective for patients with no communicating pseudocysts. Clinical success for pancreatic body or tail pseudocyst drainage was higher than that for pancreatic head pseudocyst drainage. It was found that the location of PPs predicted the success of transpapillary pseudocyst drainage. None of the other factors tested was a significant predictor of clinical success.

Background and Aim Recently, Gastroesophageal Reflux Disease Questionnaire (GerdQ) has been developed for diagnosis of GERD. However, no study investigated its value in real-world practice. This study aimed to investigate whether GerdQ can be used for diagnosis of GERD in China. Methods A national multicenter survey was undertaken; all patients who underwent first diagnostic upper endoscopy for upper gastrointestinal (GI) symptoms were included. Data including the gender, age, symptoms, and endoscopic findings were prospectively recorded. The GerdQ score was measured before endoscopic procedure. Results Totally, 8065 patients were included. One thousand four hundred and thirty-five patients (17.8%) had reflux esophagitis. Among them, 620 (43.2%) patients' GerdQ score was ≥ 8. For 2025 patients with GerdQ ≥ 8, 620 (30.6%) were found to have reflux esophagitis, but the remaining 69.4% (1405/2025) were normal. Proportions of patients with reflux esophagitis increased in cut-off range from 3–18 for GerdQ. However, 22.2% of the patients with a GerdQ score ≤ 2 also had reflux esophagitis. Twenty-eight (0.3%) patients were diagnosed to have upper GI malignancies, and 10 out of these 28 (35.7%) patients' GerdQ score was ≥ 8. Conclusions The study suggests the proportions of Chinese patients with reflux esophagitis rise up with the increase of GerdQ score, and GerdQ may be used for diagnosis of GERD. However, low GerdQ score cannot exclude the possibility of reflux esophagitis. A minority of Chinese patients has high GerdQ score but is diagnosed with malignancies, even in the absence of alarm features.

Objective To assess the value of carcinoembryonic antigen (CEA) level and cytology examination obtained by endosonography-guided fine needle aspiration (EUS-FNA) in predicting the malignancy of pancreatic mucinous cystic neoplasm (MCN). Methods The data of patients with pancreatic MCN who underwent EUS-FNA in Changhai Hospital, Second Military Medical University (Shanghai, China) from November 2005 to April 2010 were collected and analyzed. The area under receiver operating characteristic (ROC) curve of cyst fluid CEA, sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of the cytology as well as cyst fluid CEA were determined. Results Of the 20 MCNs confirmed by surgical pathology, 10 were malignant and the remainder were premalignant. Cytology had some value in differentiating malignant from premalignant MCN with a sensitivity of 60.0%, specificity of 100.0%, PPV of 100.0% and NPV of 71.4%. CEA of > 692.8 ng/mL was able to predict malignancy (P = 0.007) with sensitivity of 80.0%, specificity of 90.0%, PPV of 88.9% and NPV of 81.8%, and its area under ROC curve was 0.855. Conclusion Cyst fluid CEA level and cytology obtained by EUS-FNA are useful for predicting the malignancy of pancreatic MCN.

Background Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ( 125 I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. Objective To evaluate the safety and efficacy of direct celiac ganglion irradiation with 125 I seeds for the relief of moderate to severe pain secondary to unresectable PC. Design Prospective study. Setting Single, tertiary care referral center. Patients This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. Intervention All patients underwent EUS-guided direct celiac ganglion irradiation with 125 I seeds. Follow-up was conducted at least once weekly until death. Main Outcome Measurements Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. Results Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. Limitations Uncontrolled study. Conclusions EUS-guided direct celiac ganglion irradiation with 125 I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.

Background & Aims There have been inconsistent results published about the relationship between excess body weight, expressed as increased body mass index (BMI), and risk of colorectal adenoma (CRA). We conducted a meta-analysis to explore this relationship. We focused on whether the relationship varied based on the sex of the study subjects, study design, features of the polyps, or potential confounders, including alcohol use, nonsteroidal anti-inflammatory drug use, smoking, and exercise. Methods We identified studies by performing a literature search of Medline, EMBASE, and ISI Web of Science through July 31, 2011, and by searching the reference lists of pertinent articles. We analyzed 36 independent studies, which included 29,860 incident cases of CRA. Summary relative risks with their 95% confidence intervals (CIs) were calculated with a random-effects model. Between-study heterogeneity was assessed using Cochran's Q statistic and I 2 analyses. Results Overall, a 5-unit increase in BMI (calculated as kg/m 2 ) increased the risk for CRA (summary relative risk=1.19; 95% CI: 1.13–1.26), although there was a high level of heterogeneity among studies ( P heterogeneity I 2 = 76.8%). Subgroup analyses revealed that the increased risk of CRA in obese individuals was independent of race, geographic location, study design, sex, adenoma progression, and confounders. The association between increased BMI and risk for CRA was stronger for colon than rectal adenoma. Conclusions Based on a meta-analysis, increased BMI increases the risk for colon but not rectal adenoma. Unlike colorectal cancer, there is no sex difference in the relationship between increased BMI and risk of CRA.

OBJECTIVE: The aim of this study was to evaluate the effects and safety of different doses of ilaprazole on healthy volunteers without a Helicobacter pylori infection. METHODS: A total of 12 healthy Chinese volunteers were enrolled and divided into four groups randomly, with a 5-day treatment of oral ilaprazole 5 mg, 10 mg and 20 mg or omeprazole 20 mg, respectively. After an interval of a 14-day washout phase, each was switched to another dose group and eventually completed all four regimens. The percentage time of intragastric pH > 4 was the major index. The polymorphisms of the metabolic enzyme CYP2C19 in these volunteers were also detected. RESULTS: The percentage time of intragastric pH > 4 in the ilaprazole 5, 10 and 20 mg groups were 80.4%, 88.1% and 91.0%, respectively, during the first 24 h, compared to that of the 20 mg omeprazole group (76.6%, P > 0.05). Ilaprazole 20 mg provided a significant higher mean 24-h pH than that of the same dose of omeprazole both on Day 1 (7.78 vs 6.67, P

Background and Aim: Conventional radiological methods, including transcutaneous ultrasonography (US), computed tomography (CT), and magnetic resonance cholangiopancreatography (MRCP) are non-invasive and recommended for the detection of etiologies of acute biliary pancreatitis (ABP). There are still, however, a number of patients whose etiologies cannot be found by these methods. The value of endoscopic ultrasound (EUS) for this population is still unknown. The aim of the present study was to evaluate the role of EUS in exploring the unknown etiology of mild ABP. Methods: The data from patients with mild ABP admitted to Changhai Hospital, Shanghai, China, from June 2006 to December 2009 were retrospectively collected, and the results of the imaging methods in detecting biliary disorders were analyzed. Results: A total of 223 patients with mild ABP underwent both US and CT. Of these, 106 underwent additional MRCP. There were still 37 patients with unknown biliary etiologies, even after the use of the conventional methods mentioned earlier. EUS was conducted in 33 of these patients. Abnormalities associated with the etiology of mild ABP were found in 14 cases (42.4%) confirmed by subsequent endoscopic retrograde cholangiopancreatography, with biliary stones in 11 cases, biliary sludge in two cases, and ampullary adenocarcinoma in one case. Conclusion: The results suggest that EUS is helpful in the identification of the etiology of mild biliary pancreatitis when conventional radiological imaging is negative or equivocal.

Background Patients diagnosed with bile-duct, pancreatic-head, and ampullary carcinomas have a poor prognosis. Objective This study evaluated the potential curative efficacy and safety of intraluminal brachytherapy by using radioactive stents for palliative treatment of these patients. Design and Setting Patients with inoperable extrahepatic bile-duct (n = 2), pancreatic-head (n = 6), or ampullary (n = 3) carcinomas were treated by intraluminal implantation of radioactive stents designed according to a computerized treatment-planning system. Interventions Both radioactive stents and commonly used self-expanding metallic or plastic stents were placed in the common bile duct (CBD) of the patients. For pancreatic carcinoma, the combination of radioactive CBD and pancreatic duct (PD) stents or only a radioactive PD stent was chosen according to the tumor position. Main Outcome Measurements Survival, tumor status, and complications were assessed during the follow-up period. Results A total of 16 radioactive stents were successively placed in all 11 patients. There were no life-threatening complications. The median survival was 150 days. After 2 months of the placement of radioactive stents, 8 patients (72.7%) had stable disease, whereas 3 patients (27.3%) showed progressive disease. Conclusions The combination of radioactive stents and metallic and/or plastic stents was technically feasible and tolerable in patients with advanced tumors around the pancreatic-head area.

Background and study aims Implantation of iodine-125 ( (125)I) seeds under the guidance of endoscopic ultrasonography (EUS) has been proved to be a safe alternative treatment option for advanced pancreatic cancer. The main purpose of this study was to evaluate the feasibility and safety of EUS-guided radiation of the celiac ganglia with (125)I seeds in a porcine model. Methods Twelve domestic pigs were randomly divided into three groups. The pigs in group A had blank seeds implanted, and groups B and C had 0.4 mCi and 0.8 mCi (125)I seeds implanted, respectively. Enhanced CT scan and 3-D vascular remodeling were used to check the location of the seeds. All animals were killed and celiac ganglia were checked at 14 and at 60 days after procedure. Necrosis and apoptosis in celiac ganglia and adjacent vessels and organs were also observed. Results EUS-guided implantations of (125)I seeds in celiac plexus were successful at first procedure in 10 animals. The remaining two animals were implanted successfully the next day. No severe complications occurred in any animal and no damage was found in the surrounding organs. At day 60 after operation, the apoptotic index in the ganglia was 0.53 in the 0.4 mCi group and 0.94 in the 0.8 mCi group. No apoptotic cells were found in the control group implanted with blank seeds. Damage to vessels and surrounding organs by radioactive seeds was observed in only one pig at each time point. Conclusion EUS-guided implantation of (125)I seeds beside the celiac ganglia is a safe procedure and can induce apoptosis of local neurons. This new method may lead to an alternative treatment for pain accompanying pancreatic diseases in human.

The aim of the study was to investigate the effects of rebamipide on symptom, histology, endogenous prostaglandin, and mucosal oxygen free radicals in chronic erosive gastritis (CEG) patients by using sucralfate as a control. The trial also examined whether Helicobacter pylori infection would affect rebamipide-induced protection. A total of 453 endoscopy-confirmed CEG patients from 11 hospitals in China were enrolled in the study. They randomly received either rebamipide (100 mg t.i.d) or sucralfate (1.0 t.i.d) for 8 weeks with a ratio of 3:1. Per-protocol analysis (n = 415) showed the accumulated symptom score in the rebamipide group dropped from 5.54 +/- 0.97 to 0.80 +/- 0.47 after 8 weeks (P < 0.001 versus control). The endoscopic inflammation score in rebamipide group also decreased from 2.65 +/- 0.09 to 0.60 +/- 0.10, which showed better effects than sucralfate. It was shown a significant improvement (P < 0.01) in prostaglandin E2 (PGE(2)) contents in rebamipide-treated subjects mucosa (225.4 +/- 18.3 pg/g versus 266.7 +/- 14.7 pg/g) compared with that in sucralfate group after 8 weeks of treatment. Malondialdehyde (MDA) contents were significantly depressed both in the trial and control group. When Helicobacter pylori infection was considered, no statistically difference was found in the effect of rebamipide on either symptom or inflammation scores. In conclusion, Rebamipide demonstrated a stronger suppressive effect on the mucosal inflammation in chronic erosive gastritis than sucralfate. The gastroprotection induced by rebamipide is not influenced by H. pylori infection, which indicates its usage in the treatment of H. pylori-associated CEG.

Background. Researchers have evaluated various molecular tests for improving the differential diagnosis of cystic lesions of the pancreas.Methods. Six electronic databases were searched for articles on molecular tests for the diagnosis of pancreatic cysts. Measures of accuracy were extracted from selected articles and pooled by the random-effects model. Summary receiver operating characteristic curves were used to analyze the overall accuracy of the molecular tests. Pooled sensitivity and specificity values [95% confidence intervals] are reported.Results. The systematic review included eight studies of 428 patients in total. We determined the sensitivities and specificities of tests forKRASmutations (0.47 [0.39–0.54], 0.98 [0.93–0.99]) and loss of heterozygosity (0.63 [0.54–0.71], 0.76 [0.63–0.87]) for distinguishing mucinous from nonmucinous cysts, as well as the sensitivities and specificities of tests forKRASmutations (0.59 [0.46–0.71], 0.78 [0.71–0.85]) and loss of heterozygosity (0.89 [0.78–0.96], 0.69 [0.60–0.76]) for differentiating malignant from benign cysts.Conclusion. Tests ofKRASmutations could confirm but not exclude a diagnosis of a mucinous or malignant pancreatic cyst.

Esomeprazole is the S-isomer of omeprazole, with a stronger acid suppressive effect than omeprazole. This open, randomized crossover study was designed to evaluate the effect of esomeprazole and another proton-pump inhibitor, rabeprazole, on intragastric pH in healthy Chinese.Thirty-six healthy volunteers (26 men and 10 women, aged between 20 and 31 years) were enrolled. Subjects were given either esomeprazole 40 mg (n = 18) or rabeprazole 10 mg (n = 18) orally once daily for 5 days during the first dosing period, then the other medicine at the set dosage for the second dosing period. The two periods were separated by a 14-day washout phase. The doses were chosen according to the State Food and Drug Administration of China for the treatment of acid-related diseases. Intragastric pH was continuously monitored for 24 h on days 1 and 5 of each dosing period. CYP2C19 genotypes were analyzed to identify the extensive metabolizers (EM) and poor metabolizers (PM).The percentage of time with intragastric pH4 was significantly higher (P0.001) in subjects receiving esomeprazole than in those receiving rabeprazole in the first 4 h after administration of the first dose (70.65% vs 44.87%), at 24 h on day 1 (73.7% vs 54.8%) and at 24 h on day 5 (84.2% vs 76.2%). The median intragastric pH was also higher in subjects receiving esomeprazole than in those receiving rabeprazole in the first 6 h, day 1 and day 5 (Por= 0.001). The percentage of subjects with intragastric pH4 for at least 16 h on day 1 (63.9% vs 33.3%) and on day 5 (88.9% vs 61.1%) was higher after administration of esomeprazole than after rabeprazole (both P0.05). On genotype analysis, 28 of the subjects were EM and eight were PM. Those who were PM tended to have a higher, albeit not statistically significant, percentage of time with intragastric pH4 and the median 24-h intragastric pH than those who were EM. Both drugs were well tolerated.Esomeprazole 40 mg orally once daily is more effective and faster in increasing intragastric pH than rabeprazole 10 mg orally once daily, and thus offers a potential for improved efficacy in acid-related diseases.

To investigate in rats the role of endothelin (ET)-1 gene expression in the development and progression of acute gastric mucosal lesions (AGML) induced by stress, and the effect of BQ-123 (a special ETA receptor antagonist) on the AGML.A rat model of gastric ulcer induced by cold-restraint-stress (CRS) was used. ET-1 concentrations in the plasma and gastric mucosa were determined by radioimmunoassay (RIA), gastric mucosa blood flow (GMBF) was measured with a laser Doppler flow meter, the ulcer index (UI) was used to estimate the degree of gastric mucosa damage and the expression levels of ET-1 mRNA in the gastric mucosa were measured using dot blot and reverse transcription polymerase chain reaction (RT-PCR). Different doses of BQ-123 were administered via the left femoral vein prior to the stress in order to observe the effects of BQ-123 on the ET-1 concentrations in the plasma and gastric mucosa, the GMBF and the UI.Compared with the normal controls, the ET-1 concentrations in the plasma and gastric mucosa of the stressed rats were increased significantly (P0.05), the GMBF was decreased markedly (P0.01), and the UI increased dramatically (P0.01). There was a significant positive correlation between the gastric mucosal EF-1 concentration and the UI (r = 0.98, P0.01), and a significant negative correlation between the gastric mucosal ET-1 concentration and GMBF (r = -0.89, P0.01) and also between the UI and GMBF (r = -0.98, P0.01). The expression level of ET-1 mRNA in the gastric mucosa of the stressed rats increased significantly compared with that of the normal controls (P0.01), and there was a positive correlation between the expression of ET-1 mRNA and the ET-1 concentration in the gastric mucosa (r = 0.93, P0.01). Compared with the untreated animals, the GMBF was increased (P0.01) and the UI decreased significantly (P0.01) in the BQ-123-treated rats, and the dose of BQ-123 correlated with the degree of change in the GMBF and UI; however, the ET-1 concentrations of either the plasma or the gastric mucosa did not change markedly in the BQ-123-treated animals (P0.05).The present study showed that the level of expression of ET-1 mRNA and the synthesis of ET-1 in the gastric mucosa both increased significantly, which suggests that the increased concentration of endogenous ET-1 may be involved in the development and progression of stress ulcer (acute gastric mucosa lesion). The mechanism of action may be associated with a reduction of GMBF induced by ETAR-mediated vasoconstriction. BQ-123 can dose-dependently attenuate significantly the degree of damage to the gastric mucosa induced by stress, and may have therapeutic benefits for stress ulcer.