Miliary tuberculosis diagnosed by diffuse hepatic uptake on PET/CT and transjugular liver biopsy.

The patient was an 81-year-old man. In his 20s, he had been treated with pharmacotherapy for pulmonary tuberculosis for 1 year. He presented to the Department of Respiratory Medicine with a chief complaint of dyspnea. The possibility of respiratory disease appeared to be low, but hepatic impairment was detected. The patient was thus referred to our department. Though the cause of hepatic impairment was unknown, the soluble interleukin-2 receptor level was elevated, suggesting malignant lymphoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) revealed diffuse, homogenous, intense FDG uptake in the entire liver, and transjugular liver biopsy confirmed the diagnosis. Histopathological examination revealed an epithelioid granuloma, and auramine staining was positive for bacilli suggestive of tuberculosis. CT revealed diffuse micronodular shadows in the lung, yielding a diagnosis of miliary tuberculosis. Therefore, the patient was prescribed antituberculosis medication by the Department of Respiratory Medicine. His subsequent clinical course was good. The miliary (hepatic) tuberculosis was typical based on the diffuse, homogenous, intense FDG uptake throughout the liver observed on PET-CT.

Randomised clinical trial: 3-year interim analysis results of the VISION trial to evaluate the long-term safety of vonoprazan as maintenance treatment in patients with erosive oesophagitis.

BACKGROUND: VISION is a randomised, phase 4, open-label, parallel-group, multicentre study conducted in 33 centres in Japan. The aim of this study was to assess the long-term safety of vonoprazan for maintenance treatment of healed erosive oesophagitis versus lansoprazole. METHODS: Patients with endoscopically diagnosed erosive oesophagitis were randomised 2:1 to once-daily vonoprazan 20 mg or lansoprazole 30 mg, for a 4- to 8-week healing phase. Patients with endoscopically confirmed healing entered a 260-week maintenance phase with a once-daily starting dose of vonoprazan 10 mg or lansoprazole 15 mg. Primary endpoint was change in gastric mucosal histopathology. RESULTS: Of 208 patients (vonoprazan, n = 139; lansoprazole, n = 69) entering the healing phase, 202 entered the maintenance phase (vonoprazan, n = 135; lansoprazole, n = 67). At 3 years, 109 vonoprazan-treated and 58 lansoprazole-treated patients remained on treatment. Histopathological evaluation of gastric mucosa showed that hyperplasia of parietal, foveolar and G cells was more common with vonoprazan than lansoprazole at week 156 of the maintenance phase. There was no marked increase in the occurrence of parietal, foveolar and G cell hyperplasia among patients in the vonoprazan group from week 48 to week 156. Histopathological evaluation of the gastric mucosa also showed no neoplastic changes in either group. No new safety issues were identified. CONCLUSIONS: In this interim analysis of VISION, no new safety concerns were identified in Japanese patients with healed erosive oesophagitis receiving vonoprazan or lansoprazole as maintenance treatment for 3 years. (CT.gov identifier: NCT02679508; JapicCTI-163153; Japan Registry of Clinical Trials: jRCTs031180040).

Main causes of death in advanced biliary tract cancer.

BACKGROUND: There are no previous reports on the main causes of death in biliary tract cancer (BTC) patients. This study aimed to evaluate the main causes of death and survival rates in patients with BTC. METHODS: We retrospectively evaluated 143 patients who were diagnosed with unresectable BTC between August 2010 and March 2020. We classified the main causes of death based on laboratory data, imaging studies, and medical records. The main causes of death evaluated included liver failure, cholangitis, cachexia, other causes associated with tumor progression, and complications. We also analyzed survival rates for each main cause of death. RESULTS: After excluding patients who were lost to follow-up, living patients, and patients who had no records of laboratory data within 30 days before the date of death, 108 patients were analyzed. The main cause of death was cholangitis in 33 (30.6%), cachexia in 22 (20.4%), liver failure in 10 (9.3%), other causes associated with tumor progression in 18 (16.7%), and complications in 25 (23.2%) patients. Median overall survival (OS) was 334.0 days in the chemotherapy group and 75.0 days in the best supportive care (BSC) group. Survival analyzed according to the main cause of death was significantly different between the chemotherapy and BSC groups; OS for cachexia, cholangitis, liver failure, other causes associated with tumor progression, and complications, respectively, were 453.0, 499.0, 567.0, 205.0, and 327.5 days (p = 0.003) in the chemotherapy group and 219.0, 69.0, 34.0, 93.0, and 56.0 days (p = 0.001) in the BSC group. CONCLUSION: The main causes of death in patients with advanced BTC are cholangitis, cachexia, liver failure, other causes associated with tumor progression, and complications. Other causes associated with tumor progression in the chemotherapy group, and liver failure in the BSC group as the main causes of death shortened the survival of BTC patients.

Ability of artificial intelligence to detect T1 esophageal squamous cell carcinoma from endoscopic videos and the effects of real-time assistance.

Diagnosis using artificial intelligence (AI) with deep learning could be useful in endoscopic examinations. We investigated the ability of AI to detect superficial esophageal squamous cell carcinoma (ESCC) from esophagogastroduodenoscopy (EGD) videos. We retrospectively collected 8428 EGD images of esophageal cancer to develop a convolutional neural network through deep learning. We evaluated the detection accuracy of the AI diagnosing system compared with that of 18 endoscopists. We used 144 EGD videos for the two validation sets. First, we used 64 EGD observation videos of ESCCs using both white light imaging (WLI) and narrow-band imaging (NBI). We then evaluated the system using 80 EGD videos from 40 patients (20 with superficial ESCC and 20 with non-ESCC). In the first set, the AI system correctly diagnosed 100% ESCCs. In the second set, it correctly detected 85% (17/20) ESCCs. Of these, 75% (15/20) and 55% (11/22) were detected by WLI and NBI, respectively, and the positive predictive value was 36.7%. The endoscopists correctly detected 45% (25-70%) ESCCs. With AI real-time assistance, the sensitivities of the endoscopists were significantly improved without AI assistance (p < 0.05). AI can detect superficial ESCCs from EGD videos with high sensitivity and the sensitivity of the endoscopist was improved with AI real-time support.

Endoscopic resection for gastrointestinal tumors (esophageal, gastric, colorectal tumors): Japanese standard and future prospects.

Endoscopic resection (ER) techniques such as polypectomy, endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are widely accepted as a less invasive treatment for gastrointestinal (GI) tumors. Since there is a limit to the size that can be resected by EMR and it is often divided, it is not possible to accurately evaluate the degree of cancer progression, and the cancer remains or causes recurrence. ESD is a technology that overcomes these weaknesses. ER techniques are considered for tumors that have a very low possibility of lymph node metastasis and are suitable for en-bloc resection. As ESD became more widespread, the difficulty of treating ESD was gradually resolved by the development of technology and equipment, the curative resection rate increased, and the complication rate decreased. ER techniques have become the standard treatment for early cancer and precancerous lesions in Japan, and the therapeutic indications are expanding day by day. The indications for whether endoscopic treatment can be performed are defined by the guidelines for each organ such as the esophagus, stomach, and colorectum. In the coming aging society, it is also necessary to evaluate the indications for endoscopic treatment and invasive treatment. In addition, recent advances in endoscopic technology are making it possible to remove submucosal tumors that previously required surgery. In this review, we summarize the recent Japanese standard indications of ER for each GI location and future prospects of ER.

Effect of antiplatelet agent number, types, and pre-endoscopic management on post-polypectomy bleeding: validation of endoscopy guidelines.

BACKGROUND: It remains unclear whether type of antiplatelet (AP) therapy, AP combination therapy, and AP continuing or switching strategy affect the risk of post-polypectomy bleeding (PPB). In this study, we sought to elucidate this risk. METHODS: We analyzed 1050 patients who underwent colonoscopic polypectomy: 525 AP users and 525 controls matched for age, sex, comorbidities, concomitant non-steroidal anti-inflammatory drugs use, and polyp characteristics who did not receive antithrombotics. PPB risk was evaluated by AP number, type, and continuing or switching strategies during the peri-endoscopic period. RESULTS: In multivariate analysis, bleeding risk increased significantly as the number of AP agents used increased (monotherapy, adjusted odds ratio [aOR], 3.7; dual antiplatelet therapy (DAPT), 4.6; triple antiplatelet therapy (TAPT), 11.1) compared with controls. With monotherapy, significantly increased PPB risk was found for aspirin (aOR 4.3), thienopyridine (aOR 6.3), and cilostazol (aOR 5.9), but not for eicosapentaenoic acid or other APs (beraprost, limaprost, sarpogrelate, dilazep, or dipyridamole). With DAPT, significantly increased PPB risk was found for combination aspirin plus cilostazol, but not aspirin plus other APs. Bleeding rates for continuing monotherapy were 4.3% for aspirin and 0% for thienopyridine, cilostazol, and other APs, respectively. CONCLUSIONS: Analysis of this large polypectomy dataset showed that the use of low-dose aspirin, thienopyridine, or cilostazol and a combination of these is associated with increased PPB risk. Although PPB risk was high with DAPT or TAPT, PPB rate in any antiplatelet monotherapy even with a continuing strategy was low at < 5%.

Esophageal cancer surgery: review of complications and their management.

Esophagectomy, even with the progress in surgical technique and perioperative management, is a highly specialized surgery, associated with a high rate of complications. Early recognition and adequate treatment should be a standard of care for the most common postoperative complications: anastomotic leakage, pneumonia, atrial fibrillation, chylothorax, and recurrent laryngeal nerve palsy. Recent progress in endoscopy with vacuum and stent placement, or in radiology with embolization, has changed the management of these complications. The success of nonoperative treatments should be frequently reassessed and reoperation must be proposed in case of failure. We have summarized the clinical signs, diagnostic process, and management of the frequent complications after esophagectomy for esophageal cancer.

Vonoprazan-based triple therapy is effective for Helicobacter pylori eradication irrespective of clarithromycin susceptibility.

BACKGROUND: Helicobacter pylori causes peptic ulcers and accounts for over 90% of gastric cancers; however, eradication rates have been declining due to antimicrobial resistance. Vonoprazan (VPZ), a potassium-competitive acid blocker, produces rapid and profound gastric acid suppression and has shown promising effects in the improvement of H. pylori eradication rates. The efficacy and safety of VPZ-based triple therapy as a first-line regimen for H. pylori eradication and its relationship with clarithromycin (CAM) susceptibility were evaluated. METHODS: From May 2015 to September 2017, H. pylori-infected patients who underwent esophagogastroduodenoscopy with CAM susceptibility testing were prospectively enrolled. Patients received a 7-day triple therapy regimen (VAC) of VPZ (20 mg), amoxicillin (750 mg), and CAM (200 mg) twice daily. Eradication rates, demographics, CAM susceptibility, and safety profiles were assessed. RESULTS: VAC was administered to 146 patients (median age: 63, range: 22-85 years) (60% of whom were females) who underwent CAM susceptibility testing, and 131 patients underwent 13C-urea breath testing to evaluate eradication success. The prevalence of CAM resistance was 34.2%. The overall eradication rates of VAC in per protocol (PP) and "intention to treat" (ITT) analyses were 90.8% (n = 131) and 81.5% (n = 146), respectively. In PP analysis for CAM susceptibility, the eradication rates of VAC were comparable between CAM-sensitive (91.6%, n = 83) and CAM-resistant (89.4%, n = 47) strains. The corresponding rates from the ITT analysis were 80.0% (n = 95) and 84.0% (n = 50), respectively. No adverse events requiring discontinuation of VAC were observed. CONCLUSIONS: CAM-resistant H. pylori was prevalent in one-third of patients in the Tokyo metropolitan area. VPZ-based triple therapy was highly effective and well-tolerated irrespective of CAM susceptibility. Therefore, it could be a valuable first-line treatment regimen for H. pylori infection.

1,25-Dihydroxyvitamin D3 Inhibits Lipopolysaccharide-Induced Interleukin-6 Production by C2C12 Myotubes.

Background and Objective. 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits proinflammatory cytokines in microglial cells and monocytes. However, it is unclear whether 1,25(OH)2D3 inhibits proinflammatory cytokines in muscle cells. This study was conducted to investigate whether 1,25(OH)2D3 inhibits the production of proinflammatory cytokines, resulting in inhibition of the protein expression of E3 ubiquitin ligases and muscle protein loss. Materials and Methods. C2C12 myoblasts were proliferated in Dulbecco's modified Eagle medium (DMEM) containing 10% fetal bovine serum, and myoblasts were differentiated into myotubes in DMEM containing 2% horse serum. Myotubes were treated with 1,25(OH)2D3 for 24 h, followed by lipopolysaccharide (LPS) stimulation for 48 h. Results. Interleukin (IL)-6 protein concentrations were higher in the culture supernatant following LPS stimulation compared to that without LPS stimulation (p < 0.001). However, the IL-6 concentration was significantly lower in C2C12 myotubes following 1,25(OH)2D3 treatment than in C2C12 myotubes without 1,25(OH)2D3 treatment (p < 0.001). The myosin heavy chain (MHC), muscle atrophy F-box, and muscle ring-finger protein-1 protein levels did not significantly differ (P = 0.324, 0.552, and 0.352, respectively). We could not compare tumor necrosis factor α (TNFα) protein levels because they were below the limit of detection of our assay in many supernatant samples, including in LPS-stimulated samples. Conclusions. 1,25(OH)2D3 inhibited increases in IL-6 protein concentrations in muscle cells stimulated by LPS, suggesting that 1,25(OH)2D3 inhibits inflammation in muscle cells. The findings suggest that 1,25(OH)2D3 can prevent or improve sarcopenia, which is associated with IL-6. The TNFα protein content could not be measured, and MHC was not decreased despite LPS stimulation of C2C12 myotubes. Further studies are needed to examine the effects of higher doses of LPS stimulation on muscle cells and use more sensitive methods for measuring TNFα protein to investigate the preventive effects of 1,25(OH)2D3 on increased TNFα and muscle proteolysis.

Current surgical treatment standards for esophageal and esophagogastric junction cancer.

A number of different surgical techniques for the treatment of cancer of the esophagus and the esophagogastric junction have been proposed. Guidelines generally recommend a transthoracic approach for esophageal cancer, including Siewert type I tumors. In tumors of the proximal esophageal third, transthoracic esophagectomy may be extended to a three-field approach, including resection of cervical lymph nodes. However, the choice between transthoracic esophagectomy with intrathoracic anastomosis (Ivor Lewis esophagectomy) and the three-incision approach with cervical esophago-gastrostomy (McKeown esophagectomy) remains controversial, with guidelines varying among different countries. Furthermore, it is commonly accepted that Siewert type III tumors should be treated by extended total gastrectomy with transhiatal resection of the lower esophagus, whereas currently no consensus exists regarding the optimal surgical approach for the treatment of Siewert type II adenocarcinoma. Likewise, there is a major controversy regarding palliative and potentially curative treatment modalities in oligometastatic disease. This review deals with current surgical treatment standards for cancer of the esophagus and the eosphagogastric junction, including discussion of ongoing trials.

Potential proton pump inhibitor-related adverse effects.

Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer.

C-SH2 point mutation converts p85ß regulatory subunit of phosphoinositide 3-kinase to an anti-aging gene.

Insulin interacts with the insulin receptor, and the activated receptor promotes activity of the phosphoinositide-3 kinase (PI3K) enzyme. A decrease in insulin or insulin-like growth factor 1 (IGF-1) signaling increases the lifespan in mammalian species. We found that a point mutation in the C-SH2 domain of the p85ß regulatory subunit of PI3K results in a prolonged lifespan. In p85ß mutant cells, nerve growth factor (NGF) activates the longevity protein FOXO, and the mutant p85ß gene produces strong resistance to oxidative stress, which contributes to aging. The p85ß gene mutation causes increased serum insulin and low blood glucose in p85ß mutant transgenic mice. Our results indicate that the p85ß mutant allele alters the activity of downstream targets of PI3K by NGF and platelet-derived growth factor (PDGF) but not by insulin. We report that a point mutation in the C-SH2 domain of p85ß transforms p85ß into a novel anti-aging gene by abnormally regulating PI3K.

Next endoscopic approach for acute lower gastrointestinal bleeding without an identified source on colonoscopy: upper or capsule endoscopy?

Background and study aims We evaluated the utility of esophagogastroduodenoscopy (EGD) or capsule endoscopy (CE) as the next diagnostic approach after negative colonoscopy (CS) results in acute-onset hematochezia. Patients and methods We retrospectively analyzed 401 patients emergently hospitalized for acute hematochezia who underwent CS within 48 hours of arriving at two large emergency hospitals and in whom a definitive bleeding source was not identified. The positive endoscopic findings, requirement for additional therapeutic procedures, and 30-day rebleeding rates were compared among three strategies: EGD following CS (CS-EGD), CE following CS (CS-CE), and CS alone. Predictors of positive endoscopic findings in the CS-EGD strategy were determined. Results The rates of positive endoscopic findings and requirement for additional therapeutic procedures were 22 % and 16 %, respectively, in CS-EGD and 50 % and 28 % in CS-CE. The 30-day rebleeding rate did not significantly decrease in CS-EGD (8 %) or CS-CE (11 %) compared with CS alone (12 %). The rate of additional endoscopic therapies was lower in patients with a colonic diverticulum than in those without (CS-EGD: 3 % vs. 33 %, P  = 0.007; CS-CE: 11 % vs. 44 %, P  = 0.147). A history of syncope, low blood pressure, blood urea nitrogen/creatinine ratio of ≥ 30, and low albumin level significantly predicted EGD findings after negative CS results ( P  < 0.05). Conclusions When the definitive bleeding source is not identified by colonoscopy in patients with acute hematochezia, adjunctive endoscopy helps to identify the etiology and enables subsequent therapy, especially for patients without a colonic diverticulum. Upper gastrointestinal endoscopy is indicated for severe bleeding; other patients may be candidates for capsule endoscopy.

Increased risk of non-AIDS-defining cancers in Asian HIV-infected patients: a long-term cohort study.

BACKGROUND: Data on the long-term risks of non-AIDS defining cancers (NADCs) are limited, especially in Asians. The incidence of NADCs may correlate with the epidemiological trend of cancers or oncogenic infection in each country, and thus the target cancers would be different between Western and Asian countries. We aimed to elucidate the incidence of NADCs and its predictive factors in Asian HIV-infected patients. METHODS: Subjects were HIV-infected patients (n = 1001) periodically followed-up for 9 years on average. NADCs were diagnosed by histopathology and/ or imaging findings. Standardized incidence ratios (SIR) were calculated as the ratio of the observed to expected number of NADCs for comparison with an age-and sex-matched general population. Cox's proportional hazards model was used to estimate hazard ratios (HR). RESULTS: During the median follow-up of 9 years, the 10-year cumulative incidence of NADCs was 6.4%.At NADC diagnosis, half of patients presented at age 40-59 years and with advanced tumor stage. Compared with the age-and sex-matched general population, HIV-infected patients are at increased risk for liver cancer (SIR, 4.7), colon cancer (SIR, 2.1), and stomach cancer (SIR, 1.8). In multivariate analysis, a predictive model for NADCs was developed that included age group (40-49, 50-59, 60-69, and ≥ 70 years), smoker, HIV infection through blood transmission, and injection drug use (IDU), and HBV co-infection. The c-statistic for the NADCs predictive model was 0.8 (95%CI, 0.8-0.9, P < 0.001). The higher 10-year incidence rate of NADCs was associated with increasing prediction score. CONCLUSIONS: Liver and colon cancer risk was elevated in Asian HIV-infected individuals, similar to in Western populations, whereas stomach cancer risk was characteristically elevated in Asian populations. Half of Asian NADC patients were aged 40-59 years and had advanced-stage disease at diagnosis. Periodic cancer screening may be warranted for high-risk subpopulations with smoking habit, HIV infection through blood transmission or IDU, and HBV co-infection, and screening should be started over 40 years of age.

Long-term recurrent bleeding risk after endoscopic therapy for definitive colonic diverticular bleeding: band ligation versus clipping.

BACKGROUND AND AIMS: Very few prospective studies with over 100 samples have evaluated the long-term outcomes of endoscopic therapy for colonic diverticular bleeding (CDB). This study sought to elucidate the recurrent bleeding risk of endoscopic band ligation versus clipping for definitive CDB based on stigmata of recent hemorrhage (SRH). METHODS: Patients emergently hospitalized for acute lower GI bleeding and examined by high-resolution colonoscopy were enrolled. Better visualization of SRH from a diverticulum was obtained using a water-jet device. Endoscopic band ligation or clipping was performed as first-line treatment, and patients were prospectively followed after discharge. RESULTS: No statistical difference was found between the ligation (n = 61) and clipping (n = 47) groups in baseline characteristics or follow-up period. The probability of 1-year recurrent bleeding was 11.5% in the ligation group versus 37.0% in the clipping group (P = .018). No patients required surgery or experienced perforation. One patient in the ligation group experienced diverticulitis the next day. In patients with recurrent bleeding within 7 days, the recurrent bleeding site was the same diverticulum, and ulceration was found in the ligation group on repeat colonoscopy. In patients with recurrent bleeding after 2 months, repeat colonoscopy identified that the recurrent bleeding site was different, and scar formation was seen in the ligation group. The left side of the colon was an independent predictor for recurrent bleeding in the ligation group but not in the clipping group. CONCLUSIONS: Band ligation for definitive CDB has better outcomes than clipping during long-term follow-up after endoscopic therapy, probably because of complete elimination of the diverticulum. CDB can recur at the same diverticulum in the short term but at a different diverticulum in the long term.

Current and future perspectives in the management of gastroesophageal reflux disease.

Although the prevalence of gastroesophageal reflux disease (GERD) used to be lower in East Asia as compared to Western countries, it has recently been increasing, most likely due to the socioeconomic development in the East. The prevalence of both GERD and functional gastrointestinal disorders (FGIDs) ranges between 10% and 25% worldwide and there are distinct subgroups of patients with overlapping of GERD and FGIDs. However, the true prevalence of an overlap between GERD and FGIDs can be determined only when a formal pathophysiological evaluation has been performed. Nocturnal reflux symptoms have a significant impact on patients' sleep quality and quality of life. Although proton pump inhibitors (PPIs) can improve both reflux and sleep-related symptoms, the relationship between nocturnal reflux events and sleep disturbance is not fully understood. GERD plays an important role in the pathogenesis of lung fibrosis, and PPIs or fundoplication may decrease the likelihood of pulmonary exacerbation or even improve pulmonary function. Refractory reflux symptoms without esophagitis have become one of the most common presentations of GERD in gastroenterology clinics. There are several new medical therapies, and endoscopic as well as laparoscopic techniques that have been increasingly used in these patients. The selection of options should be tailored and individualized based on the pathophysiology of refractory GERD.

Post-polypectomy bleeding and thromboembolism risks associated with warfarin vs direct oral anticoagulants.

AIM: To verify the validity of the endoscopy guidelines for patients taking warfarin or direct oral anticoagulants (DOAC). METHODS: We collected data from 218 patients receiving oral anticoagulants (73 DOAC users, 145 warfarin users) and 218 patients not receiving any antithrombotics (age- and sex-matched controls) who underwent polypectomy. (1) We evaluated post-polypectomy bleeding (PPB) risk in patients receiving warfarin or DOAC compared with controls; (2) we assessed the risks of PPB and thromboembolism between three AC management methods: Discontinuing AC with heparin bridge (HPB) (endoscopy guideline recommendation), continuing AC, and discontinuing AC without HPB. RESULTS: PPB rate was significantly higher in warfarin users and DOAC users compared with controls (13.7% and 13.7% vs 0.9%, P < 0.001), but was not significantly different between rivaroxaban (13.2%), dabigatran (11.1%), and apixaban (13.3%) users. Two thromboembolic events occurred in warfarin users, but none in DOAC users. Compared with the continuing anticoagulant group, the discontinuing anticoagulant with HPB group (guideline recommendation) had a higher PPB rate (10.8% vs 19.6%, P = 0.087). These findings were significantly evident in warfarin but not DOAC users. One thrombotic event occurred in the discontinuing anticoagulant with HPB group and the discontinuing anticoagulant without HPB group; none occurred in the continuing anticoagulant group. CONCLUSION: PPB risk was similar between patients taking warfarin and DOAC. Thromboembolism was observed in warfarin users only. The guideline recommendations for HPB should be re-considered.

Validation of the American Gastroenterological Association guidelines on management of intraductal papillary mucinous neoplasms: more than 5 years of follow-up.

OBJECTIVES: Recent guidelines suggest that imaging surveillance be conducted for 5 years for patients with at most one high-risk feature. If there were no significant changes, surveillance is stopped. We sought to validate this follow-up strategy. METHODS: In study 1, data were analysed for 392 patients with intraductal papillary mucinous neoplasms (IPMNs) and at most one high-risk feature who were periodically followed up for more than 1 year with imaging tests. In study 2, data were analysed for 159 IPMN patients without worsening high-risk features after 5 years (stop surveillance group). RESULTS: In study 1, pancreatic cancer (PC) was identified in 12 patients (27.3%) in the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) indication group and none in the non-EUS-FNA indication group (P < 0.01). In the EUS-FNA indication group, 11 patients (25%) died, whereas 29 (8.3%) died in the non EUS-FNA indication group (P < 0.01). In study 2 (stop surveillance group), PC was identified in three patients (1.9%) at 84, 103 and 145 months. CONCLUSIONS: PC risk and mortality for IPMNs not showing significant change for 5 years is likely to be low, and the non-EUS-FNA indication can provide reasonable decisions. However, three patients without worsening high-risk features for 5 years developed PC. The stop surveillance strategy should be reconsidered. KEY POINTS: • The AGA guidelines provide reasonable clinical decisions for the EUS-FNA indication. • In stop surveillance group, PC was identified in 3 patients (1.9%). • In stop surveillance group, 2 of 3 PC patients died from PC. • Risk of pancreatic cancer in "stop surveillance" group is not negligible.

Therapeutic endoscopy-related GI bleeding and thromboembolic events in patients using warfarin or direct oral anticoagulants: results from a large nationwide database analysis.

OBJECTIVE: To compare the risks of postendoscopy outcomes associated with warfarin with direct oral anticoagulants (DOACs), taking into account heparin bridging and various types of endoscopic procedures. DESIGN: Using the Japanese Diagnosis Procedure Combination database, we identified 16 977 patients who underwent 13 types of high-risk endoscopic procedures and took preoperative warfarin or DOACs from 2014 to 2015. One-to-one propensity score matching was performed to compare postendoscopy GI bleeding and thromboembolism between the warfarin and DOAC groups. RESULTS: In the propensity score-matched analysis involving 5046 pairs, the warfarin group had a significantly higher proportion of GI bleeding than the DOAC group (12.0% vs 9.9%; p=0.002). No significant difference was observed in thromboembolism (5.4% vs 4.7%) or in-hospital mortality (5.4% vs 4.7%). The risks of GI bleeding and thromboembolism were greater in patients treated with warfarin plus heparin bridging or DOACs plus bridging than in patients treated with DOACs alone. Compared with percutaneous endoscopic gastrostomy, patients who underwent endoscopic submucosal dissection, endoscopic mucosal resection and haemostatic procedures including endoscopic variceal ligation or endoscopic injection sclerotherapy were at the highest risk of GI bleeding among the 13 types of endoscopic procedures, whereas those who underwent lower polypectomy endoscopic sphincterotomy or endoscopic ultrasound-guided fine needle aspiration were at moderate risk. CONCLUSION: The risk of postendoscopy GI bleeding was higher in warfarin than DOAC users. Heparin bridging was associated with an increased risk of bleeding and did not prevent thromboembolism. The bleeding risk varied by the type of endoscopic procedure.

Effect of low-dose aspirin use on pancreatic cancer development and morphological changes on imaging in IPMN: A long-term cohort study.

BACKGROUND: Aspirin use may reduce the incidence of pancreatic cancer (PC), but no data are available regarding its chemopreventive effects on intraductal papillary mucinous neoplasm (IPMN). We aimed to determine whether low-dose aspirin (LDA) reduces PC development and morphological changes on imaging in IPMN patients. METHODS: A cohort of 448 IPMN patients periodically followed up with imaging tests was analyzed. We used one-to-two propensity score matching to adjust for differences between an LDA group (n = 63) and a non-LDA group (n = 385). Outcomes included increasing cyst diameter, increasing main pancreatic duct (MPD) diameter, mural nodule (MN) appearance and PC development. RESULTS: After matching, 63 LDA and 126 non-LDA patients were selected. During follow-up (median, 5.5 years), no significant differences were found in increasing cyst diameter, MN appearance, or PC development. However, there were significantly fewer cases of increasing MPD diameter in the LDA group (4.8% vs. 12.7%; p = 0.02). After adjustment for age and sex, LDA still decreased the risk of increasing MPD diameter (hazard ratio, 0.17; p = 0.02). CONCLUSION: Our results do not support a chemopreventive effect of LDA on PC development. However, LDA reduces further MPD dilation in IPMN patients.