Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE).

Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naïve hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555.

Non-alcoholic fatty liver diseases and risk of colorectal neoplasia.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with colorectal neoplasia. Yet, NAFLD ranges from simple steatosis to steatohepatitis with advanced fibrosis. AIM: To investigate the risk of colorectal neoplasia according to the presence and severity of NAFLD. METHODS: A total of 26 540 asymptomatic adults who underwent same day first-time colonoscopy and abdominal ultrasonography as a health check-up programme were analysed. NAFLD was diagnosed by ultrasonography. Advanced colorectal neoplasia was defined as an invasive cancer or adenoma that was at least 10 mm in diameter, had high-grade dysplasia, or had villous histological characteristics or any combination thereof. RESULTS: NAFLD patients had a higher prevalence of any colorectal neoplasia (38.0% vs. 28.9%) and advanced colorectal neoplasia (2.8% vs. 1.9%) compared to those without NAFLD. In a multivariable model adjusted for age, sex, smoking, alcohol, body mass index, first-degree family history of colorectal cancer, aspirin use and metabolic factors, the odd ratios comparing patients with NAFLD to those without were 1.10 [95% confidence interval (CI): 1.03-1.17] for any colorectal neoplasia and 1.21 (95% CI: 0.99-1.47) for advanced colorectal neoplasia. When NAFLD patients were further stratified according to the non-invasive parameters of liver disease severity, the risk of any colorectal neoplasia or advanced colorectal neoplasia was higher for those with severe liver diseases than those with mild liver diseases. CONCLUSIONS: The presence and severity of NAFLD were closely associated with any colorectal neoplasia and advanced colorectal neoplasia, suggesting that clinicians should be aware of the increased risk of colorectal neoplasia in patients with NAFLD.

A phase 3b study of sofosbuvir plus ribavirin in treatment-naive and treatment-experienced Korean patients chronically infected with genotype 2 hepatitis C virus.

In Korea, patients with chronic hepatitis C virus (HCV) infection are typically treated with pegylated interferon-alpha plus ribavirin, but interferons are contraindicated in many patients and are often poorly tolerated, particularly by the elderly and those with advanced liver disease. No interferon-free treatment regimens are approved in Korea. Sofosbuvir is an oral nucleotide analog inhibitor of the HCV nonstructural 5B RNA polymerase. It is approved in the USA, European Union and Japan for treating a number of HCV genotypes, including genotype 2. Genotype 2 has a seroprevalence of 38-46% in Korea. This single-arm, phase 3b study (NCT02021643) examined the efficacy and safety of sofosbuvir plus ribavirin (12-week duration) in chronic genotype 2 HCV-infected treatment-naive and treatment-experienced Korean patients with and without cirrhosis. The proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12) was 97% (125/129), with 96% (101/105) of treatment-naive and 100% (24/24) of treatment-experienced patients achieving SVR12. Two patients experienced virologic failure (n = 1, on-treatment failure; n = 1, relapse). No patient discontinued study treatment due to an adverse event (AE). The most common treatment-emergent AEs were headache (18%, 23/129) and pruritus (15%, 19/129). Few patients had grade 3 AEs (5%, 6/129) or grade 3 laboratory abnormalities (12%, 15/129). No grade 4 AE was reported. These data suggest that 12 weeks of treatment with the all-oral, interferon-free regimen of sofosbuvir plus ribavirin is effective and well tolerated in Korean patients with chronic genotype 2 HCV infection.

Influence of hepatitis B virus reactivation on the recurrence of HBV-related hepatocellular carcinoma after curative resection in patients with low viral load.

It is unclear whether the reactivation of hepatitis B virus (HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resection in patients with chronic hepatitis B. The aim of this study was to identify the influence of HBV reactivation on the recurrence of hepatitis B-related HCC after curative resection in patients with low viral load (HBV DNA <2000 IU/mL). We retrospectively analysed a total of 130 patients who underwent curative resection for HBV-related early stage HCC (single nodule; <5 cm/two or three nodules; <3 cm) with pre-operative HBV DNA levels <2000 IU/mL with serial HBV DNA tests. The predictive factors including HBV reactivation for the recurrence of HBV-related HCC after curative resection were investigated. Fifty-three patients (41%) had HBV reactivation after resection among 130 patients. HBV reactivation was observed in 22 of 53 patients with undetectable baseline HBV DNA and in 31 of 77 patients with detectable baseline HBV DNA. Cumulative recurrence rates after resection at 1, 2 and 3 years were 17.0%, 23.3% and 31.4%, respectively. The multivariable analysis demonstrated that the risk factors for the recurrence were the presence of microvascular invasion (hazard ratio (HR) 2.62, P = 0.003), multinodularity (HR 4.61, P = 0.005), HBV reactivation after resection (HR 2.03, P = 0.032) and HBeAg positivity (HR 2.06, P = 0.044). HBV reactivation after curative resection is associated with the recurrence of HBV-related HCC in patients with low viral load.

Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in 1965 patients with cirrhosis and ascites: a propensity score matched cohort study.

BACKGROUND: The risk of spontaneous bacterial peritonitis (SBP) associated with proton pump inhibitor (PPI) use has been raised in cirrhotic patients with ascites. However, this is based on case-control studies, often with a small series. AIM: To determine whether PPI use increases the risk of SBP using a large cohort. METHODS: This retrospective cohort study included 1965 cirrhotic patients with ascites diagnosed between January 2005 and December 2009. The SBP incidence rate was compared between the PPI and non-PPI groups before and after propensity score matching to reduce the effect of selection bias and potential confounders. Multivariate analysis was conducted to confirm the association of PPI use with SBP. RESULTS: After excluding 411 patients, 1554 were analysed. Among them, 512 patients (32.9%) were included in the PPI group. The annual SBP incidence rate was higher in the PPI group than in the non-PPI group (10.6% and 5.8%, P = 0.002) before matching. Indications for PPI use and dose of PPI were similar between patients with and without SBP. In the propensity score matched cohort (402 pairs), the SBP incidence rate was also higher in the PPI group than in the non-PPI group (10.8% vs. 6.0%, P = 0.038). Multivariate analysis revealed that PPI use (Hazard ratio 1.396; 95% confidence interval, 1.057-1.843; P = 0.019) was the independent risk factor for SBP. CONCLUSIONS: Proton pump inhibitor use significantly increases the risk of spontaneous bacterial peritonitis in cirrhotic patients with ascites. Proton pump inhibitor use should be undertaken with greater caution and appropriately in patients with cirrhosis.

Expanded criteria for liver transplantation in patients with hepatocellular carcinoma.

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL.

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.

PURPOSE: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). PATIENTS AND METHODS: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated. RESULTS: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors. CONCLUSION: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma.

OBJECTIVE: To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC). METHODS: From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion. RESULTS: The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI-CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05). CONCLUSIONS: Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease. ADVANCES IN KNOWLEDGE: There were discrepancies of approximately 5 mm in gated MRI-CT fusion planning for HCC patients.

Effectiveness of locoregional therapy before living donor liver transplantation in patients with hepatocellular carcinoma who meet the Milan criteria.

BACKGROUND: Many patients are diagnosed with hepatocellular carcinoma (HCC) within the Milan criteria. In Korea, these patients are preferentially treated with locoregional therapy (LRT) instead of living donor liver transplantation. We investigated the effectiveness of LRT in liver transplant recipients who met the Milan criteria at the time of HCC diagnosis and investigated risk factors for HCC recurrence. METHODS: We retrospectively reviewed the medical records of patients diagnosed with HCC who met the Milan criteria between 2002 and 2008. RESULTS: We performed 101 liver transplants for HCC during the study period. Seventy-one patients (70%) underwent pretransplant LRT. The disease-free survival rates at 1, 3, and 5 years in patients who received LRT were 96.6%, 93.1%, and 93.1%, and in those who did not receive LRT, 94.2%, 83.4%, and 83.4%, respectively. There were no differences between the 2 groups. Multivariate analysis showed that a low Model for End-Stage Liver Disease (MELD) score and microvascular invasion were independent predictors of HCC recurrence after transplantation. The MELD scores and rate of microvascular invasion were not statistically different in patients with or without previous LRT. CONCLUSION: Pretransplant LRT for patients with HCC who met the Milan criteria at the time of diagnosis did not provide a clear benefit with respect to HCC recurrence after transplantation. If patients have suitable living donors, those who meet the Milan criteria should undergo a liver transplantation as soon as possible.

Clinical significance of pre-S mutations in patients with genotype C hepatitis B virus infection.

We investigated the overall and site-specific prevalence of pre-S mutations and its clinical significance in patients with genotype C hepatitis B virus (HBV) infection. Three hundred subjects were included: 50 asymptomatic carriers (AC), 87 chronic hepatitis (CH), 91 liver cirrhosis (LC) and 72 hepatocellular carcinoma (HCC). Pre-S mutations were determined by nucleotide sequence analysis. Possible correlations between pre-S mutations and clinical/virological parameters were examined. Pre-S mutations were detected in 82 cases (27.3%); it was more frequently found in HCC (43.1%) and LC (35.2%) group than in the CH (20.7%) and AC (2.0%) group. Pre-S2 deletion was the most commonly found mutation (10.7%), followed by pre-S2 start codon mutation (9.7%), pre-S1-S2 deletion (3.0%) and both pre-S2 deletion and start codon mutation (2.7%). Pre-S2 deletion and pre-S2 start codon mutation were more frequently detected in advanced diseases (LC and HCC). Pre-S mutations were associated with older age and higher rates of positive HBV DNA (>/=0.5 pg/mL). Advanced disease and positive HBV DNA were shown to be independent predictors of pre-S mutations by logistic regression analysis. These findings suggest that pre-S mutations, especially pre-S2 deletions and pre-S2 start codon mutations, are common in patients with genotype C HBV infection and are associated with advanced liver disease and active viral replication.

Non-surgical management of microperforation induced by EMR of the stomach.

BACKGROUND: Perforation and bleeding are major complications associated with gastric endoscopic mucosal resection. Evident perforation during endoscopic mucosal resection can be managed by endoscopic clipping. However, management of microperforation is not well established. PATIENT AND METHOD: From January 2002 to June 2004, 109 early gastric cancers and 300 adenomas were treated with endoscopic mucosal resection. Iatrogenic perforations occurred in 4.16% (n=17) patients. Following exclusion of four evident perforations, microperforation was observed in 3.18% (n=13) patients. The clinical features of microperforation in patients were retrospectively reviewed. RESULTS: In a total of 13 microperforation cases, 2 patients were managed surgically. The remaining patients successfully recovered without surgical management. In the case of 11 patients without surgery, 7 experienced abdominal pain, which required analgesics, 2 patients experienced mild discomfort and 2 patients experienced no symptoms. A body temperature above 37.5 degrees C was observed in 9.1% (n=1) patients and leucocytosis above 9000 microL-1 was in 72.7% (n=8) patients. The mean duration of nasogastric tube drainage was 2.36+/-1.03 days, of fasting 4.18+/-1.17 days, of intravenous antibiotics 5.55+/-1.44 days and of hospitalisation 7.45+/-1.04 days. CONCLUSION: Microperforation induced by gastric endoscopic mucosal resection can be managed successfully using a non-surgical approach including fasting, nasogastric tube drainage and intravenous antibiotics.

Nonsurgical treatment of abdominal or pelvic abscess in consecutive patients with Crohn's disease.

BACKGROUND: There is little agreement about the efficacy of nonsurgical treatment for abscess associated with Crohn's disease. Furthermore, there is no study on characteristics of abscess or patient that nonsurgical treatment could be worth trying as initial treatment. AIMS: To evaluate the outcome of nonsurgical treatment in Crohn's disease-related abscess and identify factor leading to failure of nonsurgical treatment of this complication. PATIENTS: Twenty-four patients, who consecutively admitted for Crohn's disease-related abscess to our institution during a 7-year period, underwent nonsurgical treatment as initial therapy. METHODS: Outcome data such as recurrence and intractability, and clinical features were retrospectively analysed. Univariate analysis with patient-related factors and abscess-related factors was performed for risk factor identification. RESULTS: Median follow-up period was 47.5 months. Of the eligible patients, 19 patients were treated medically and 5 patients underwent percutaneous catheter drainage with medical treatment. Overall success rate of nonsurgical treatment in our centre was 66.7%. The cumulative recurrence rate at 7 months was 12.5%. All recurrences occurred within 7 months from complete resolution on follow-up imaging. Univariate analysis showed that the significant factors which lead to failure of nonsurgical treatment were presence of associated fistula and concurrent steroid use (P=0.019 and P=0.019, respectively). CONCLUSION: Nonsurgical treatment can be considered as initial treatment modality for the Crohn's disease-related abscess without concurrent steroid therapy or relevant fistula.

The role of follow-up endoscopy after total gastrectomy for gastric cancer.

BACKGROUND: Follow-up endoscopy after total gastrectomy for gastric cancer is commonly performed without there being any definite evidence of clinical relevance. Therefore, we investigated the role of the upper endoscopic examinations after total gastrectomy for gastric cancer. METHODS: The medical records of 212 early gastric cancer (EGC) patients and 622 advanced gastric cancer (AGC) patients who underwent follow-up endoscopic examination after total gastrectomy between 1994 and 2001 were reviewed. RESULTS: Two of 212 EGC patients and 233 of 622 AGC patients revealed tumour recurrence at all sites. All the endoscopically accessible local tumour recurrences (n=24) were found in the AGC group. Anastomosis site stenosis was detected in 72 of 834 patients. CONCLUSION: Follow-up endoscopy after total gastrectomy for gastric cancer is useful in detecting complications and tumour recurrence. However, this procedure has a limited role in the clinical management and overall survival for patients with recurrent gastric adenocarcinoma.

Outcomes in patients with hepatopulmonary syndrome undergoing liver transplantation.

Hepatopulmonary syndrome (HPS) is a condition of significant hypoxia due to intrapulmonary shunting (IPS) in patients with advanced liver disease. Reversibility of HPS after liver transplantation (LT) has been suggested, but the results of LT for HPS remain poorly defined. We studied 78 patients with decompensated liver disease who underwent LT after a preoperative evaluation including contrast echocardiography. We compared the baseline characteristics and outcomes after LT in patients with HPS (n = 13) with those of patients without HPS (n = 65, controls). Before LT, prolongation of prothrombin time was more severe and an advanced Child-Pugh class were more frequent among HPS, patients compared with controls (INR 2.5 +/- 0.8 vs 1.9 +/- 0.7, P = .01; Child-Pugh class A:B:C = 0%:31%:69% vs 14%:65%:21%, P < .01). After LT, no significant differences were observed between the two groups in: clinical outcomes, duration of endotracheal intubation (4.5 +/- 7.7 vs 4.4 +/- 15.0 days), duration of intensive care unit stay (12.0 +/- 8.7 vs 14.4 +/- 19.4 days), duration of total hospital stay (40.0 +/- 33.5 vs 39.8 +/- 23.0), rate of pulmonary complications (7.7% vs 9.2%), or 3-month survival rates (92.3% vs 86.1%). These findings suggest that the presence of HPS does not significantly affect LT outcomes in patients with decompensated liver disease.

Factors affecting graft survival after living donor liver transplantation.

Living donor liver transplantation (LDLT) has been considered as an alternative option to resolve the shortage of cadaveric donor organs, despite the ethical aspects of the donor procedure. The objective of this study was to analyze the risk factors affecting graft survival in LDLT. From June 1996 to December 2002, 141 patients who underwent LDLT were retrospectively analyzed. Graft survival rates were 82.5%, 80%, 77.3%, and 77.3% at 6 months, 1 year, 3 years, and 5 years, respectively. The factors influencing graft survival in univariate analysis were graft-to-recipient body weight ratio (GRWR) less than 0.8% (P = .0009), intraoperative transfusion of more than six packed RBC units in addition to the use of cell saver amounts (P = .0001), left lobe grafts in adults causing small-for-size situations (P = .0135), and donor age (P = .0472). The multivariate analysis demonstrated that GRWR less than 0.8% (P = .002) and intraoperative transfusion of more than six packed RBC units (P = .014) were independent factors that decreased graft survival rates. The graft selection of greater than 0.8% of GRWR and reduction of intraoperative RBC transfusion improve graft survival.

Can we expand the Milan criteria for hepatocellular carcinoma in living donor liver transplantation?

INTRODUCTION: The Milan criteria, namely, tumors 5 cm or less in diameter in patients with single hepatocellular carcinoma (HCC), no more than 3 tumor nodules, and each 3 cm or less in diameter in patients with multiple tumors, are accepted for cadaveric liver allocation. However, in living donor liver transplantation (LDLT), graft donation may only depend on the donor's intention. The aim of this study was to elucidate the feasibility of Milan criteria in LDLT. MATERIALS AND METHODS: From January 2001 to December 2002, 46 cases of liver transplantation (LT) for HCC included 5 hospital mortalities and 3 cadaveric transplantations, all of which were excluded. We classified the patients into Group I cases that met the Milan criteria and Group II cases that did not meet the Milan criteria. The analyses examined tumor-related risk factors affecting recurrence and survival, such as tumor size, number of tumor nodules, and presence of microvascular and macrovascular invasion. RESULTS: Twenty-one cases belonged to Group I and 17 to Group II. There was no significant difference in the recurrence or survival rates between Groups I and II. The risk factors affecting recurrence were macrovascular invasion and tumor size (5 cm). The number of tumor nodules and microvascular invasion did not appear to affect recurrence. The risk factor affecting survival was macrovascular invasion. CONCLUSION: We suggest that in selected cases the Milan criteria could be extended to increase the number of tumor nodules as long as the HCC were small and did not macrovascular invasion.

Long-term stress and Helicobacter pylori infection independently induce gastric mucosal lesions in C57BL/6 mice.

BACKGROUND: Long-term psychological stresses may have a role in the pathogenesis of peptic ulcer. However, the interaction between stress and Helicobacter pylori infection in the development of peptic ulcer is not established. The aim of this study was to elucidate the roles of long-term stress and H. pylori infection in the development of gastric mucosal lesions in mice. METHODS: The Sydney strain (SS1) of H. pylori was inoculated into the stomach of C57BL/J6 mice. Twelve weeks later, mice with or without H. pylori infection were exposed to long-term repeated water-immersion-restraint stress (WIRS) for 12 h per day, 3 times per week, for 8 weeks. Gastric mucosal lesions were evaluated both macroscopically (ulcer index) and microscopically (Updated Sydney System). RESULTS: The long-term WIRS induced mild inflammation, oedema, interstitial haemorrhage and superficial erosions in the stomach of mice both with and without H. pylori infection. The degree of mucosal inflammation or atrophy in H. pylori-infected mice was not influenced by the stress. In the mice without H. pylori infection, the ulcer index of the stressed mice was greater than that of non-stressed mice (1.66 +/- 0.39 versus 0.17 +/- 0.08, P = 0.007). In the mice with H. pylori infection, the ulcer index (mean +/- s(x)) of the stressed mice was also greater than that of non-stressed mice (2.31 +/- 0.59 versus 0.64 +/- 0.22, P = 0.027). CONCLUSIONS: The present study showed that long-term stress can induce gastric mucosal inflammation and erosions, and this effect may occur independently of H. pylori infection.

Increased risk of peristomal wound infection after percutaneous endoscopic gastrostomy in patients with diabetes mellitus.

BACKGROUND: Results of prospective studies on the effect of prophylactic antibiotics before percutaneous endoscopic gastrostomy are conflicting. Factors for increased risk of peristomal wound infection have not been clearly identified. AIM: To evaluate the incidence of complications of percutaneous endoscopic gastrostomy and to determine the predictors of wound infection. PATIENTS AND METHODS: Percutaneous endoscopic gastrostomy was performed on 134 patients in different disease groups between January 1996 and June 2000. Medical records were carefully reviewed for demographic data, indications for percutaneous endoscopic gastrostomy, use of prophylactic antibiotics, complications and comorbid conditions predisposing to wound infection. RESULTS: Of 134 patients, 22 (16.4%) developed complications after percutaneous endoscopic gastrostomy Wound infection, the most common complication, occurred in 19 patients (14.2%) and Pseudomonas aeruginosa was the most frequently isolated microorganism. In univariate analysis, non-malignant disease and diabetes mellitus were significantly associated with peristomal wound infection after percutaneous endoscopic gastrostomy. In multivariate analysis, only diabetes mellitus was an independent risk factor for the development of peristomal wound infection after percutaneous endoscopic gastrostomy (p = 0.035) CONCLUSIONS: Patients with diabetes mellitus have a higher risk of peristomal wound infection after percutaneous endoscopic gastrostomy.