Evaluation of the Validity of Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

GOALS: We evaluated the validity of endoscopic transpapillary gallbladder drainage (ETGBD) as a bridging therapy prior to elective Lap-C for the patients with acute cholecystitis (AC). BACKGROUND: The Tokyo Guidelines 2018 recommend early laparoscopic cholecystectomy (Lap-C) for patients with AC, however, some patients require the preoperative drainage because of inadequate for early Lap-C du to background and comorbidities. STUDY: We performed a retrospective cohort analysis using data from our hospital records from 2018-2021. In total, 71 cases of 61 patients with AC underwent ETGBD. RESULTS: The technical success rate was 85.9%. Patients in the failure group had more complicated branching of the cystic duct. The length of time until feeding was started and until WBC levels normalized, and the length of hospital stay were significantly shorter in the success group. The median waiting period for surgery was 39 days in the ETGBD success cases. The median operating time, amount of bleeding, and length of postoperative hospital stay were 134 min, 83.2g, and 4 days, respectively. In patients who underwent Lap-C, the waiting period for surgery and the operating time were similar between the ETGBD success and failure groups. However, the temporary discharge period after drainage and the length of postoperative hospital stay were significantly longer in the patients with ETGBD failure. CONCLUSIONS: Our study revealed that ETGBD has equivalent efficacy prior to elective Lap-C despite some challenges that lower its success rate. Preoperativ ETGBD can improve patient quality of life by eliminating the need for a drainage tube.

Effects of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma: survey findings of the Japanese Red Cross Liver Study Group.

AIM: To investigate, in a large number of cases at multiple institutions, the effects and limitations of antiviral therapy for hepatitis C following treatment of hepatocellular carcinoma (HCC) in clinical practice. METHODS: Retrospective analysis was performed of 112 patients who had received interferon (IFN) for treating hepatitis C following treatment of HCC and were registered with the Japanese Red Cross Liver Study Group. Factors that may influence recurrence and survival rates were investigated. RESULTS: Factors involved in prevention of recurrence were: surgical resection as HCC treatment, platelet and α-fetoprotein (AFP) levels prior to IFN administration, IFN adherence and post-IFN AFP level. Multivariate analysis showed post-IFN AFP level to be an independent factor. Factors involved in prolonging survival were: IFN adherence, IFN response (sustained viral response), pre-IFN alanine aminotransferase and AFP levels, post-IFN AFP level and absence of recurrence. Multivariate analysis showed absence of recurrence to be an independent factor. Although IFN adherence was involved in recurrence and survival, ribavirin adherence was not. IFN was suggested to be involved in preventing recurrence and improving survival due not only to its anti-viral effect, but also its antitumor effect. CONCLUSION: Although complete prevention of HCC recurrence is difficult, the most important factor affecting first recurrence is the AFP level at 6 months after the conclusion of antiviral treatment. The survival rate improves dramatically if the hepatitis C virus is eliminated, but the most important factor for improving survival is absence of recurrence.

Peroxisome proliferator-activated receptor gamma (PPARgamma) regulates trefoil factor family 2 (TFF2) expression in gastric epithelial cells.

Although trefoil factor family 2 (TFF2) plays a critical role in the defense and repair of gastric mucosa, the regulatory mechanism of TFF2 expression is not fully understood. In this study, we investigated the regulation of TFF2 expression by peroxisome proliferator-activated receptor gamma (PPARgamma) in gastric epithelial cells. MKN45 gastric cells were used. TFF2 mRNA expression was analyzed by real-time quantitative RT-PCR. The promoter sequence of the human TFF2 gene was cloned into pGL3-basic vector for reporter gene assays. Ciglitazone was mainly used as a specific PPARgamma ligand. MKN45 cells expressed functional PPARgamma proteins. Endogenous TFF2 mRNA expression and TFF2 reporter gene transcription was significantly up-regulated by ciglitazone in a dose-dependent manner. Reporter gene assays showed that two distinct cis-elements are involved in the response to PAPRgamma activation. Within one of these element (nucleotides -558 to -507), we identified a functional peroxisome proliferator responsive element (PPRE) at -522 (5'-GGGACAAAGGGCA-3'). Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay confirmed the binding of PPARgamma to this sequence. Another element (nucleotides -407 to -358) appeared to be a composite enhancer element indirectly regulated by PPARgamma and a combination of these two cis-elements was required for the full response of the human TFF2 gene expression to PPARgamma. These data demonstrate that human TFF2 gene is a direct target of PPARgamma in gastric epithelial cells. Since TFF2 is a critical gastroprotective agent, PPARgamma may be involved in the gastric mucosal defense through regulating TFF2 expression in humans.

Regulation of TFF3 expression by homeodomain protein CDX2.

Although trefoil factor family 3 (TFF3) plays an important role in protecting the intestinal mucosa, the regulatory mechanisms of its expression are not fully understood. Since homeodomain protein CDX2 has been reported to be critically involved in the development and differentiation of intestinal epithelium, we examined whether CDX2 affects the expression of TFF3. The transcription of human TFF3 reporter genes was significantly up-regulated by the transient overexpression of CDX2 in COS-7 cells and AGS gastric cells. Electrophoretic mobility shift assay revealed the presence of at least two CDX-binding sites within the human TFF3 promoter. Deletion analysis showed the relative importance of the proximal CDX-binding site at -63. We also detected the up-regulation of endogenous TFF3 mRNA expression in AGS cells stably transfected with CDX2 expression vectors. These results suggest that CDX2 plays a key role in the expression of TFF3 in the intestine and perhaps in intestinal metaplasia of the stomach.

Endoscopic balloon dilation for stenotic lesions in Crohn's disease.

BACKGROUND/AIMS: Endoscopic balloon dilation (EBD) can serve as an alternative to surgery for intestinal stenosis associated with Crohn's disease (CD). However, there has been controversy regarding the efficacy and safety of EBD. Here we sought to determine the therapeutic efficacy and safety of EBD for intestinal stenosis in CD. MATERIALS AND METHODS: Of 43 patients with CD accompanied by intestinal stenosis, 30 underwent EBD. These 30 patients were examined retrospectively in terms of the scope passage rate, surgery-free rate, and whether or not the observation of the distal intestinal tract influenced the therapeutic strategy. RESULTS: The overall scope passage and surgery-free rates were 90.0% and 76.7%, respectively. There were no statistically significant differences in the site of the dilated intestinal tract among groups. Patients who had inflammation in the distal intestinal tract alone after EBD accounted for 56.7%. The rate of re-dilation was 46.7%, and time until re-dilation was 6.6±3.6 months. CONCLUSION: EBD was associated with favorable short-term and long-term outcomes and good safety. Observation of the distal intestinal tract influenced the decision-making process for therapeutic strategies. The results of this study suggest that EBD may allow the postponement or even avoidance of surgery, enabling not only intestinal dilation but also the evaluation of mucosal healing to be performed. Thus, EBD is considered to be an effective alternative treatment for intestinal stenotic lesions in patients with CD.

Multicenter study of endoscopic preoperative biliary drainage for malignant distal biliary obstruction.

AIM: To determine the optimal method of endoscopic preoperative biliary drainage for malignant distal biliary obstruction. METHODS: Multicenter retrospective study was conducted in patients who underwent plastic stent (PS) or nasobiliary catheter (NBC) placement for resectable malignant distal biliary obstruction followed by surgery between January 2010 and March 2012. Procedure-related adverse events, stent/catheter dysfunction (occlusion or migration of PS/NBC, development of cholangitis, or other conditions that required repeat endoscopic biliary intervention), and jaundice resolution (bilirubin level < 3.0 mg/dL) were evaluated. Cumulative incidence of jaundice resolution and dysfunction of PS/NBC were estimated using competing risk analysis. Patient characteristics and preoperative biliary drainage were also evaluated for association with the time to jaundice resolution and PS/NBC dysfunction using competing risk regression analysis. RESULTS: In total, 419 patients were included in the study (PS, 253 and NBC, 166). Primary cancers included pancreatic cancer in 194 patients (46%), bile duct cancer in 172 (41%), gallbladder cancer in three (1%), and ampullary cancer in 50 (12%). The median serum total bilirubin was 7.8 mg/dL and 324 patients (77%) had ≥ 3.0 mg/dL. During the median time to surgery of 29 d [interquartile range (IQR), 30-39 d]. PS/NBC dysfunction rate was 35% for PS and 18% for NBC [Subdistribution hazard ratio (SHR) = 4.76; 95%CI: 2.44-10.0, P < 0.001]; the pig-tailed tip was a risk factor for PS dysfunction. Jaundice resolution was achieved in 85% of patients and did not depend on the drainage method (PS or NBC). CONCLUSION: PS has insufficient patency for preoperative biliary drainage. Given the drawbacks of external drainage via NBC, an alternative method of internal drainage should be explored.

Endoscopic ultrasonography can diagnose distal biliary strictures without a mass on computed tomography.

AIM: To assess the diagnostic ability of endoscopic ultrasonography (EUS) for evaluating causes of distal biliary strictures shown on endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP), even without identifiable mass on computed tomography (CT). METHODS: The diagnostic ability of EUS was retrospectively analyzed and compared with that of routine cytology (RC) and tumor markers in 34 patients with distal biliary strictures detected by ERCP or MRCP at Dokkyo Medical School Hospital from December 2005 to December 2008, without any adjacent mass or eccentric thickening of the bile duct on CT that could cause biliary strictures. Findings considered as benign strictures on EUS included preservation of the normal sonographic layers of the bile duct wall, irrespective of the presence of a mass lesion. Other strictures were considered malignant. Final diagnosis of underlying diseases was made by pathological examination in 18 cases after surgical removal of the samples, and by clinical follow-up for > 10 mo in 16 cases. RESULTS: Seventeen patients (50%) were finally diagnosed with benign conditions, including 6 "normal" subjects, while 17 patients (50%) were diagnosed with malignant disease. In terms of diagnostic ability, EUS showed 94.1% sensitivity, 82.3% specificity, 84.2% positive predictive value, 93.3% negative predictive value (NPV) and 88.2% accuracy for identifying malignant and benign strictures. EUS was more sensitive than RC (94.1% vs 62.5%, P = 0.039). NPV was also better for EUS than for RC (93.3% vs 57.5%, P = 0.035). In addition, EUS provided significantly higher sensitivity than tumor markers using 100 U/mL as the cutoff level of carbohydrate antigen 19-9 (94.1% vs 53%, P = 0.017). On EUS, biliary stricture that was finally diagnosed as malignant showed as a hypoechoic, irregular mass, with obstruction of the biliary duct and invasion to surrounding tissues. CONCLUSION: EUS can diagnose biliary strictures caused by malignant tumors that are undetectable on CT. Earlier detection by EUS would provide more therapeutic options for patients with early-stage pancreaticobiliary cancer.

Up-regulation of TFF1 (pS2) expression by TNF-alpha in gastric epithelial cells.

BACKGROUND AND AIM: TFF1 (pS2) is expressed at a high level in gastric epithelial cells and plays an important role in protecting the gastric mucosa. However, the regulatory mechanisms of TFF1 expression are not fully understood. The aim of this study was to investigate the effect of TNF-alpha, a representative proinflammatory cytokine, on TFF1 expression. METHODS: MKN45 and AGS cells, derived from human gastric carcinoma, were used. Endogenous TFF1 mRNA expression was analyzed by real-time quantitative RT-PCR. The sequences of the human TFF1 promoter were cloned into the pGL3-basic vector and reporter gene assays were performed. Nuclear factor (NF)-kappaB activity was monitored using a reporter vector that contained multiple copies of NF-kappaB responsive element upstream of the luciferase gene. Interaction between NF-kappaB and TFF1 cis-element was examined by electophoretic mobility shift assay (EMSA). RESULTS: TNF-alpha activated NF-kappaB and up-regulated endogenous TFF1 mRNA expression as well as the transcription of the TFF1 reporter genes in a dose-dependent manner. IL-1beta, another proinflammatory cytokine, also up-regulated TFF1 expression. TNF-alpha responsive element was mapped between -342 and -147 of the human TFF1 promoter and a putative NF-kappaB binding site was identified at -231. When this element was deleted, the reporter genes became almost insensitive to TNF-alpha treatment. EMSA showed binding of NF-kappaB to this element. CONCLUSIONS: Inflammatory stimuli that activate NF-kappaB appear to up-regulate TFF1 expression in gastric epithelial cells. This mechanism may aid in the protection of the gastric mucosa under inflammatory conditions.