Safety/efficacy of atezolizumab + bevacizumab during anti-platelet/anticoagulation therapy in unresectable hepatocellular carcinoma.

BACKGROUND AND AIMS: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants. METHODS: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined. RESULTS: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis. CONCLUSION: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants.

Machine learning for individualized prediction of hepatocellular carcinoma development after the eradication of hepatitis C virus with antivirals.

BACKGROUND AND AIMS: Accurate risk stratification for hepatocellular carcinoma (HCC) after achieving a sustained viral response (SVR) is necessary for optimal surveillance. We aimed to develop and validate a machine learning (ML) model to predict the risk of HCC after achieving an SVR in individual patients. METHODS: In this multicenter cohort study, 1742 patients with chronic hepatitis C who achieved an SVR were enrolled. Five ML models were developed including DeepSurv, gradient boosting survival analysis, random survival forest (RSF), survival support vector machine, and a conventional Cox proportional hazard model. Model performance was evaluated using Harrel' c-index and was externally validated in an independent cohort (977 patients). RESULTS: During the mean observation period of 5.4 years, 122 patients developed HCC (83 in the derivation cohort and 39 in the external validation cohort). The RSF model showed the best discrimination ability using seven parameters at the achievement of an SVR with a c-index of 0.839 in the external validation cohort and a high discriminative ability when the patients were categorized into three risk groups (P <0.001). Furthermore, this RSF model enabled the generation of an individualized predictive curve for HCC occurrence for each patient with an app available online. CONCLUSIONS: We developed and externally validated an RSF model with good predictive performance for the risk of HCC after an SVR. The application of this novel model is available on the website. This model could provide the data to consider an effective surveillance method. Further studies are needed to make recommendations for surveillance policies tailored to the medical situation in each country. IMPACT AND IMPLICATIONS: A novel prediction model for HCC occurrence in patients after hepatitis C virus eradication was developed using machine learning algorithms. This model, using seven commonly measured parameters, has been shown to have a good predictive ability for HCC development and could provide a personalized surveillance system.

Vonoprazan versus proton pump inhibitors for postendoscopic submucosal dissection bleeding in the stomach: a multicenter population-based comparative study.

BACKGROUND AND AIMS: The effectiveness of vonoprazan relative to that of proton pump inhibitors (PPIs) after gastric endoscopic submucosal dissection (ESD) is unclear. Although previous studies used post-ESD ulcer healing as the outcome measure, post-ESD bleeding rate is the most objective and appropriate outcome measure because it has less ascertainment bias. We aimed to compare the post-ESD bleeding rates between vonoprazan and PPIs. METHODS: This nationwide population-based retrospective cohort study was conducted between 2014 and 2018 and involved 9 hospitals. After 2 days of intravenous PPI administration, either vonoprazan or PPI was administrated from postoperative day 2 to 30. RESULTS: Overall, data of 1715 patients (627 patient pairs) were analyzed through propensity score matching. The vonoprazan group had significantly lower post-ESD bleeding rates than the PPI group (overall, 11.9% vs 17.2%, P = .008; bleeding between days 2 and 30, 7.8% vs 11.8%, P = .015). The readmission rate because of post-ESD bleeding was lower in the vonoprazan group (2.4% vs 4.1%, P = .081). Blood transfusion (2.1% vs 3.0%, P = .15) and additional surgery because of delayed perforation (.5% vs 1.0%, P = .32) were not significantly different between the 2 groups. No deaths within 30 days occurred in both groups. On Cox regression analysis, vonoprazan use, lesion location (antrum), aspirin use, direct oral anticoagulant use, and Charlson Comorbidity Index (≥2) were associated with an increased risk of post-ESD bleeding within 30 days. CONCLUSIONS: Vonoprazan has a lower post-ESD bleeding rate than PPIs. Further prospective studies are required to confirm these results.

Chemoprevention of Oesophageal Squamous-Cell Carcinoma and Adenocarcinoma: A Multicentre Retrospective Cohort Study.

BACKGROUND: Oesophageal cancer comprises 2 different histological variants: oesophageal squamous-cell carcinoma (ESCC) and adenocarcinoma (EAC). While there are multiple therapeutic options for both types, patients with advanced or metastatic oesophageal cancer still suffer from poor prognosis. AIMS: The study aimed to examine the association between the risk of oesophageal cancer and medications and to estimate the chemopreventive effects of commonly used drugs. METHODS: A multicentre retrospective cohort study was conducted using data from 9 hospital databases of hospitalized patients between 2014 and 2019. The primary outcomes were ESCC and EAC. The association of oesophageal cancer with drug use and clinical factors was evaluated. Odds ratios (ORs) were adjusted for age, sex, Charlson comorbidity index scores, and smoking with/without gastro-oesophageal reflux disease. RESULTS: The use of proton pump inhibitors (PPIs) (adjusted OR [aOR] 0.48, p < 0.0001), aspirin (aOR 0.32, p < 0.0001), cyclooxygenase-2 inhibitor (COX2I) (aOR 0.70, p = 0.0005), steroid (aOR 0.19, p < 0.0001), statin (aOR 0.43, p < 0.0001), and metformin (aOR 0.42, p < 0.0001) was associated with a lower risk of ESCC than that in non-use. The use of aspirin (aOR 0.33, p = 0.0006) and steroids (aOR 0.54, p = 0.022) was associated with a lower risk of EAC than that in non-use. CONCLUSION: COX2Is, statins, metformin, and PPIs could help in prevention of ESCC, and aspirin and steroids may be chemopreventive for both types of oesophageal cancer.

Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers?

BACKGROUND AND AIMS: Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes. CONCLUSIONS: Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.

Identification of histopathological and clinical spectrum of diabetic kidney disease based on an unsupervised hierarchical clustering analysis of elderly autopsy specimens.

AIM: Diabetic kidney disease (DKD), a chronic kidney disease caused by diabetes and other comorbidities, is the leading cause of end-stage renal disease. The pathogenesis of DKD is diverse and influenced by various causes, some but not all of which cause proteinuria. Some factors such as hypertension can modify DKD. Therefore, the spectrum of DKD is difficult to elucidate and remains unsolved. This study aims to classify and characterize DKD. METHODS: We examined autopsy specimens from type 2 diabetes mellitus (DM) (n = 44) and non-DM (n = 21) groups. RESULTS: The frequency of interstitial fibrosis and tubular atrophy was higher in patients with proteinuric DKD than in those with non-proteinuric DKD. The presence of polar vasculosis was associated with hypertension in DKD. In addition, an unsupervised hierarchical clustering analysis revealed the spectrum of renal histopathology findings for more-proteinuric and less-proteinuric DKD. With changes in the diagnostic criteria for hypertension and advances in antihypertensive drugs, the pathogenesis of DKD may be changing. Furthermore, a decision tree model suggested how diabetes, hypertension, and dyslipidemia interacted in predicting the characteristics of DKD. CONCLUSION: Polar vasculosis is a good indicator of the presence of DM and hypertension. Furthermore, the histopathological and clinical spectrum of DKD were related to the interaction of diabetes, hypertension, and dyslipidemia. These histopathological and clinical results may help to show the range of patient characteristics when conducting clinical trials and could help to determine whether chronic kidney disease is caused by DM or some other cause.

IFN-λ3 as a host immune response in acute hepatitis E virus infection.

BACKGROUND AND AIM: Hepatitis E virus (HEV) is mainly transmitted orally, either waterborne or zoonotic foodborne. Intestinal viruses such as rotavirus are known to induce type III interferon (IFN) in the gastrointestinal (GI) tract where type III IFN dominantly functions in comparison with type I IFN. Therefore, the aim of this study is to investigate the significance of type III IFN (IFN-λ3) in acute hepatitis E. METHODS: IFN-λ3 and HEV RNA levels in the sera of patients with acute HEV infection and in the supernatant of HEV-inoculated cells were measured, using an in-house high-sensitivity method and reverse transcription-polymerase chain reaction, respectively. RESULTS: High serum IFN-λ3 levels were found in the early phase of acute HEV infection, which normalized after resolution. Interestingly, serum IFN-λ3 levels correlated well with serum HEV RNA titers in the same sera, both of which showed the peak before the robust increase of transaminases. In vitro experiments demonstrated that HEV replicated well in the cells with little IFN-λ3 induction (Caco-2, A549) and recombinant IFN-λ3 inhibited HEV replication in a dose-dependent manner. In contrast, in HT-29 cells, a colon cancer cell line, HEV poorly replicated and induced IFN-λ3 in a titer-dependent manner. CONCLUSIONS: These clinical and experimental observations suggest that HEV induced IFN-λ3 as a host innate immune response, which may play a protective role against HEV.

Investigating the origin and global dispersal history of hepatitis E virus genotype 4 using phylogeographical analysis.

BACKGROUND & AIMS: Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach. METHODS: The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy. RESULTS: The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries. CONCLUSIONS: Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.

Association of coronary artery calcification with liver fibrosis in Japanese patients with non-alcoholic fatty liver disease.

AIMS: Cardiovascular events are the leading cause of death among patients with non-alcoholic fatty liver disease (NAFLD), but their relationship remains unclear. This study examined the association between coronary atherosclerosis and liver fibrosis, represented by the coronary artery calcification (CAC) score and non-invasive fibrosis markers, respectively. METHODS: Among 698 patients with chest pain or electrocardiographic abnormalities who underwent coronary computed tomography (CT) between April 2006 and March 2010, those with known liver disorders or history of emergency coronary angioplasty were excluded, leaving 366 patients for this study. Diagnosis of NAFLD was based on abdominal CT and history of alcohol consumption. Subjects with CAC of 100 AU or more were categorized into the high-risk group for cardiovascular events. Patient records were examined for clinical parameters including CAC score and non-invasive fibrosis marker FIB-4 index. RESULTS: Ninety-four patients (25.7%) had NAFLD. In this group, univariate analysis identified old age, high diastolic blood pressure, high liver to spleen ratio and high FIB-4 index as risk factors for cardiovascular events and multivariate analysis identified age of 66 years or older and FIB-4 index of 2.09 or more as the significant risk factors. For the observation period until August 2014, the cumulative proportion of PCI performance was significantly higher in patients with FIB-4 of 2.09 or more than those with FIB-4 of less than 2.09. CONCLUSION: The progression of arteriosclerosis and that of liver fibrosis may be associated in NAFLD patients. The FIB-4 index can be easily determined and thus can be a useful marker for predicting cardiovascular events in NAFLD patients.

High genomic similarity between European type hepatitis E virus subgenotype 3e strains isolated from an acute hepatitis patient and a wild boar in Mie, Japan.

A 67-year-old male living in Tsu city, Mie prefecture, Japan was referred to our hospital for further examination of acute liver injury and was diagnosed as having clinical hepatitis E virus (HEV) infection in January 2010. The HEV strain (HE-JA11-1701) isolated from the patient belonged to genotype 3 and European-type subgenotype 3e. It was presumed that the patient had been infected from a wild boar (Sus scrofa leucomystax) because he consumed meat/viscera from a wild boar that he had captured himself as a hunter approximately 2 months before disease onset. A specimen of the boar meat/viscera that the patient had ingested was not available. However, the HE-JA11-1701 strain was 99.8% identical within the 412-nucleotide sequence of the open reading frame 2 region to a HEV strain (JBOAR012-Mie08) that had been recovered from a wild boar captured near the patient's hunting area in 2008. A phylogenetic analysis confirmed that the two HEV strains had a close genetic relationship and were segregated into subgenotype 3e, supported by a high bootstrap value of 99%. Of note, the HE-JA11-1701 and JBOAR012-Mie08 strains were remotely related to the 3e strains reported in Japan and European countries, with a nucleotide difference of 7.9-13.9%, reinforcing the uniqueness of the 3e strains obtained in the present study. These results strongly support our speculation that the patient developed acute hepatitis E via consumption of HEV-infected boar meat/viscera. Genetic analyses of HEV strains are useful for tracing infectious sources in sporadic cases of acute hepatitis E.

Usefulness of assessment of the Clinical Frailty Scale and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items at the time of initiation of maintenance hemodialysis in older patients with chronic kidney disease.

INTRODUCTION: We examined whether the Clinical Frailty Scale (CFS), a widely adopted tool for stratifying the degree of frailty, and the Dementia Assessment Sheet for Community-based Integrated Care System 21-items (DASC-21), a simple tool for simultaneous assessment of impaired cognition and impaired ADL, at the time of initiation of hemodialysis is useful tool of older patients for the outcome and prognosis. METHODS: Data for 101 patients aged 75 years or older (mean age, 84.3 years) with ESRD who were initiated on hemodialysis and could be followed up for a period of 6 months were reviewed. RESULTS: The 6-month survival curves showed a significantly higher number of deaths in the frailty (CFS≥5) group than in the normal to vulnerable (CFS<5) group (p<0.01). The CFS level was also significantly higher (6.5±1.5) in patients who died within 6 months of dialysis initiation as compared with that (4.6±1.7) in patients who survived (p<0.01). On the other hand, the total score of DASC-21 was related to need for inpatient maintenance dialysis (p<0.01). The total score on the DASC-21 were found as showing significant correlations with the CFS level. The IADL outside the home was identified in the DASC-21 sub-analyses as being correlated with CFS. CONCLUSIONS: The CFS and the DASC-21 appeared to be a useful predictive tool of outcome and prognosis for older patients being initiated on hemodialysis. Assessment by the CFS or the DASC-21 might be useful for selecting the renal replacement therapy by shared decision-making and for advance care planning.

Severe Drug-Induced Interstitial Lung Disease After Administration of Osimertinib as Adjuvant Treatment for Resected EGFR-Mutated NSCLC: A Case Report.

Osimertinib administration has been approved as an adjuvant treatment after complete surgical resection in patients with EGFR-mutated NSCLC. This article presents the first report of life-threatening postoperative osimertinib-induced interstitial lung disease. An 83-year-old male patient underwent right upper lobectomy (pathologic stage IIA) and osimertinib (80 mg/d) was initiated on postoperative day 75. On day 44 of osimertinib administration, chest computed tomography revealed diffuse ground-glass opacities; accordingly, osimertinib-induced interstitial lung disease was diagnosed. Steroid pulse therapy was initiated using a high-flow nasal cannula to treat dyspnea and hypoxemia, rapidly improving the respiratory status and imaging findings; moreover, the patient's clinical course was excellent. This case report suggests that the postoperative occurrence of severe osimertinib-induced interstitial lung disease is a crucial factor that must be considered in patient decision-making regarding perioperative treatment.

Epidemiological and molecular analyses of a non-seasonal outbreak of acute icteric hepatitis E in Bangladesh.

Acute hepatitis due to hepatitis E virus (HEV) is endemic in Bangladesh, but its epidemiological characteristics and virological features remain obscure. An outbreak of acute icteric hepatitis E occurred in Rajshahi, Bangladesh during 2010 when 200 patients with visible jaundice visited physicians within a period of 1 month (January-February). Clinical and epidemiological data were collected from these patients using questionnaires. Nucleic acids were isolated from 15 patients who were selected at random to ascertain their HEV genotypes. Near-complete nucleotide sequences of the HEV genome were detected in two patients and partial ORF2 regions in the other 13 patients. All patients tested positive for IgM antibodies to HEV but negative for other hepatitis viruses. Most patients were icteric and complained of vomiting, fever, itching, and abdominal pain. All 15 HEV sequences formed a single cluster within genotype 1a. Two of the 7,186-nt HEV sequences were 99.8% identical. This is the first study to report the clinical, epidemiological, and molecular characterization of an outbreak of acute hepatitis E in Bangladesh.

Female intravesical foreign body penetrating the bladder wall: A rare case of traditional Asian hair stick kanzashi.

A female in her thirties inserted an Asian traditional hair stick, kanzashi, into her urinary bladder for sexual gratification. We need to know that everyday objects can become bladder foreign bodies and how to manage them properly.

Association of probiotic use with nivolumab effectiveness against various cancers: A multicenter retrospective cohort study.

BACKGROUND: Previous studies have revealed an association between probiotic use and effectiveness of immune checkpoint inhibitors in renal and lung cancers. However, little is known regarding other cancers, including gastrointestinal cancer. METHODS: To address this issue, we conducted a multicenter retrospective cohort study and the duration of nivolumab treatment for various cancers was compared between probiotic users and non-users. RESULTS AND CONCLUSIONS: In total, 488 patients who received nivolumab therapy were included. In all cancers, no significant differences in treatment duration of nivolumab were observed between probiotic users and non-users (median 62.0 vs. 56.0, hazard ratio = 1.02, p = 0.825), whereas probiotic use, compared with non-use, in patients with gastric cancer was significantly associated with a longer duration of nivolumab treatment (55.0 vs. 31.0 days, hazard ratio = 0.69, p = 0.039). In conclusion, probiotics may improve the response to nivolumab and potentially prolong progression-free survival in patients with gastric cancer.

New findings regarding the epidemic history and population dynamics of Japan-indigenous genotype 3 hepatitis E virus inferred by molecular evolution.

BACKGROUND: Since previous studies have investigated the population dynamics of Japan-indigenous genotype 3 hepatitis E virus (HEV) using virus sequences, more nucleotide sequences have been determined, and new techniques have been developed for such analysis. AIMS: To prevent future hepatitis E epidemic in Japan, this study aimed to elucidate the cause of past HEV expansion. METHODS: The epidemic history of Japan-indigenous genotype 3 HEV was determined using the coalescent analysis framework. Bayesian skyline plot (BSP) and Bayesian estimate of phylogeny with relaxed molecular clock models were calculated using Markov chain Monte Carlo sampling. RESULTS: Japan-indigenous strains consist of New World strains (subtype 3a), Japanese strains (3b) and European strains (3e). The oldest lineage, 3b, appeared around 1929. Lineages 3a and 3e appeared around 1960. BSPs indicated similar radical population growth of the 3a and 3b lineages from 1960 to 1980. CONCLUSIONS: Population dynamics of the three lineages shared some common characteristics, but had distinguishing features. The appearance of 3a and 3e lineages coincides with the increase of large-race pig importation from Europe and the USA after 1960. The epidemic phase of 3a and 3b strains from 1960 to 1980 could be related to increased opportunity for HEV infection arising from large-scale pig breeding since 1960. Our observations revealed new findings concerning the close relationship between the epidemic history of Japan-indigenous genotype 3 HEV and the improvement of the Japanese pig industry. Infection control in pig farms should be an effective method of preventing HEV infection in humans.

Rare case of a patient with testicular torsion complicated by acute pneumonia, requiring emergency surgery, during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has been causing delay in patient arrival at hospital and starting surgery. We report a delay in a case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic in Japan. CASE PRESENTATION: A 17-year-old Japanese boy presented to our emergency room with acute left scrotum pain and fever in January 2021. It took 2.5 h to transfer him. Physical examination and color Doppler ultrasonography revealed left testicular torsion. Chest computed tomography indicated acute pneumonia. He successfully underwent surgical detorsion 7.5 h after symptom onset, with COVID-19 preventive measures in place. A negative polymerase chain reaction test result for COVID-19 was revealed after surgery. CONCLUSION: We experienced a rare case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic. Special attention should be paid to preventing infection and surgery delay to avoid testicular loss.

Effectiveness and safety of chemotherapy for patients with malignant gastrointestinal obstruction: A Japanese population-based cohort study.

BACKGROUND: The impacts of chemotherapy on patients with malignant gastrointestinal obstructions remain unclear, and multicenter evidence is lacking. AIM: To evaluate the effectiveness and safety of chemotherapy in patients with unresectable malignant gastrointestinal obstructions. METHODS: We conducted a multicenter retrospective cohort study that compared the chemotherapy group who received any chemotherapeutics after interventions, including palliative surgery or self-expandable metal stent placement, for unresectable malignant gastrointestinal obstruction vs the best supportive care (BSC) group between 2014 and 2019 in nine hospitals. The primary outcome was overall survival, and the secondary outcomes were patency duration and adverse events, including gastrointestinal perforation and gastrointestinal bleeding. RESULTS: In total, 470 patients in the chemotherapy group and 652 patients in the BSC group were analyzed. During the follow-up period of 54.1 mo, the median overall survival durations were 19.3 mo in the chemotherapy group and 5.4 mo in the BSC group (log-rank test, P < 0.01). The median patency durations were 9.7 mo [95% confidence interval (CI): 7.7-11.5 mo] in the chemotherapy group and 2.5 mo (95%CI: 2.0-2.9 mo) in the BSC group (log-rank test, P < 0.01). The perforation rate was 1.3% (6/470) in the chemotherapy group and 0.9% (6/652) in the BSC group (P = 0.567). The gastrointestinal bleeding rate was 1.5% (7/470) in the chemotherapy group and 0.5% (3/652) in the BSC group (P = 0.105). CONCLUSION: Chemotherapy after interventions for unresectable malignant gastrointestinal obstruction was associated with increased overall survival and patency duration.

Biliary Peritonitis Caused by Spontaneous Bile Duct Rupture in the Left Triangular Ligament of the Liver after Endoscopic Sphincterotomy for Choledocholithiasis.

Spontaneous bile duct rupture is a rare condition in adults, with only 70 cases reported. Increased bile duct wall pressure may lead to rupture and biliary peritonitis. In this patient, the bile duct ruptured in the hepatic left triangular ligament. A 91-year-old man underwent endoscopic retrograde cholangiopancreatography for choledocholithiasis and endoscopic retrograde biliary drainage (ERBD) placement. One week later, removal of the ERBD and common bile duct stones and an endoscopic sphincterotomy (EST) were performed. Four days later, the patient had abdominal pain, increased inflammatory reaction, and jaundice. Abdominal computed tomography showed ascites, bile duct dilatation and fluid collection under the liver (10 cm in diameter). Emergency surgery was performed to drain the fluid. On laparotomy, encapsulated biliary ascites was seen. To search for the site of the leak, after cholecystectomy, a tube (C-tube) was inserted into the common bile duct via cystic duct stump. Because of uncontrollable bleeding, after packing with surgical gauze, the operation was temporarily stopped. The next day, reoperation was performed. Intraoperative cholangiography with contrast dye revealed the perforation site in the left triangular ligament and a partial resection was performed. Bile excretion from the C-tube was subsequently observed, but the patient's jaundice did not improve. Although endoscopic retrograde cholangiopancreatography revealed that the EST site was normal, ERBD was placed again, and the jaundice gradually improved. Although EST was performed in this case, biliary peritonitis resulting from spontaneous bile duct rupture occurred. This case was very informative because biliary perforation may occur even after EST.

Nonsteroidal anti-inflammatory drugs prevent gastric cancer associated with the use of proton pump inhibitors after Helicobacter pylori eradication.

BACKGROUND AND AIM: Proton pump inhibitors (PPIs) are a potential cause of gastric carcinogenesis after Helicobacter pylori eradication. Thus, appropriate management including chemoprevention is required. The aim of this study was to evaluate the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and the incidence of post-eradication gastric cancer in PPI users. METHODS: A multicenter retrospective cohort study was conducted. Patients who used a PPI (≥30 days) after H. pylori eradication between 2014 and 2019 were analyzed in nine hospital databases. Gastric cancer incidence was a primary outcome, and their association with NSAIDs use and clinical factors was evaluated. Hazard ratios were adjusted by age, sex, smoking, and Charlson Comorbidity Index. RESULTS: During the mean follow-up period of 2.38 years, 1.13% (31/2431) of all patients developed gastric cancer. The cumulative incidence of gastric cancer in PPI users was 0.25% at 1 year, 0.51% at 3 years, and 1.09% at 5 years in the NSAID users and 0.89% at 1 year, 2.32% at 3 years, and 3.61% at 5 years in nonusers. NSAIDs were associated with a lower gastric cancer risk (adjusted hazard ratio = 0.28, P = 0.005). No gastric cancer was observed in the cyclooxygenase-2 inhibitor users (n = 256). NSAID use with high dose and long duration was significantly associated with a lower incidence of gastric cancer. CONCLUSION: NSAIDs were associated with a 60% decrease in the gastric cancer incidence in H. pylori-eradicated PPI users, with dose and duration response effects. NSAIDs may be effective for chemoprevention against PPI-related gastric cancer.