IgG4-related pancreatobiliary diseases could be associated with onset of pancreatobiliary cancer: A multicenter cohort study.

BACKGROUND: The risk and prognosis of pancreatobiliary cancer and in patients with autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) remain unclear. Therefore, we retrospectively investigated the risk of pancreatobiliary cancer and prognosis in patients with AIP and IgG4-SC. METHODS: Patients with AIP and IgG4-SC at seven centers between 1998 and 2022 were investigated. The following data were evaluated: (1) the number of cancers diagnosed and standardized incidence ratio (SIR) for pancreatobiliary and other cancers during the observational period and (2) prognosis after diagnosis of AIP and IgG4-SC using standardized mortality ratio (SMR). RESULTS: This study included 201 patients with AIP and IgG4-SC. The mean follow-up period was 5.7 years. Seven cases of pancreatic cancer were diagnosed, and the SIR was 8.11 (95% confidence interval [CI]: 7.29-9.13). Three cases of bile duct cancer were diagnosed, and the SIR was 6.89 (95% CI: 6.20-7.75). The SMR after the diagnosis of AIP and IgG4-SC in cases that developed pancreatobiliary cancer were 4.03 (95% CI: 2.83-6.99). CONCLUSIONS: Patients with autoimmune pancreatitis and IgG4-SC were associated with a high risk of pancreatic and bile duct cancer. Patients with AIP and IgG4-SC have a worse prognosis when they develop pancreatobiliary cancer.

Franseen Needles May Be Promising for Improving the Sampling Adequacy of EUS-FNA for Subepithelial Lesions.

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is useful in diagnosing subepithelial lesions (SELs), and adequate tissue sampling is necessary to differentiate between benign and malignant diseases to determine therapeutic strategies. This study aimed to evaluate sampling adequacy and diagnostic performance of EUS-FNA for SELs with Franseen needles. This retrospective study enrolled 130 patients who underwent EUS-FNA with a 22-gauge needle for SELs from January 2010 to March 2021. We compared sampling adequacy and predictive factors influencing the sampling adequacy of EUS-FNA for SELs between Franseen and conventional needles. The sampling adequacy rates were 95.0% (38/40) with Franseen needles and 76.7% (69/90) with conventional needles (p = 0.011). The mean number of punctures with Franseen needles (2.80) was significantly less than that with conventional needles (3.42) (p < 0.001). In the multivariate analysis, the use of Franseen needles (p = 0.029; odds ratio [OR], 5.37; 95% confidence interval [CI], 1.18−23.36) was an independent factor influencing the sampling adequacy. Compared to conventional needles, the Franseen needle could play a vital role in accurately diagnosing SELs by yielding better sampling adequacy and reducing the number of passes.

Learning Curve of Endoscopic Retrograde Cholangiopancreatography Using Single-Balloon Enteroscopy.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) in patients with surgically altered anatomy is technically difficult. Extensive training is required to develop the ability to perform this procedure. AIMS: To investigate the learning curve of single-balloon-assisted enteroscopy ERCP (SBE-ERCP). METHODS: We conducted a retrospective, observational case series at a single center. We evaluated the SBE-ERCP procedures between April 2011 and February 2021. The main outcomes were the rate of reaching the target site and the success rate of the entire procedure. These parameters were additionally expressed as a learning curve. RESULTS: A total of 687 SBE-ERCP procedures were analyzed. The learning curve was analyzed in blocks of 10 cases. In this study, seven endoscopists, experts in conventional ERCP, were included. The overall SBE-ERCP procedural success rate was 92.2% (634/687 cases). Combining all data from individual endoscopists' evaluation periods, the insertion and success rates of the SBE-ERCP procedures gradually increased with increased experience performing SBE-ERCP. The insertion success rates for the number of SBE-ERCP cases (< 20, 21-30, > 30) were 82.9%, 92.9%, and 94.3%, respectively; the procedure success rates were 74.3%, 81.4%, and 92.9%, respectively. The endoscopists who had performed > 30 SBE-ERCP cases had a success rate of ≥ 90%. CONCLUSIONS: Our results suggest that performing > 30 cases is one of the targets for conventional ERCP experts to become competent in performing SBE-ERCP in patients with a surgically altered anatomy.

IgG4-related sclerosing cholangitis may be a risk factor for cancer.

BACKGROUND/PURPOSE: The relationship between autoimmune pancreatitis (AIP) and malignancy has been reported. However, the potential risk for cancer in patients with immunoglobulin 4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is unclear. The present study aimed to evaluate the incidence of cancer in IgG4-SC patients. METHODS: We retrospectively collected clinical data for 121 patients diagnosed with IgG4-SC from 7 hospitals. We calculated the standardized incidence ratio (SIR) of cancer in IgG4-SC patients based on the national cancer rates. The SIR of the period after the diagnosis of IgG4-SC were calculated. RESULTS: The mean follow-up period was 6.4 years, with 121 IgG4-SC patients. During the follow-up period, 26 patients had cancer, and 29 cancers were diagnosed. The SIR of cancer after the diagnosis of IgG4-SC was 1.90 (95% confidence interval [CI] 1.67-2.21). The SIR of pancreatic and bile duct cancer was 10.30 and 8.88, respectively. The SIR of cancer in <1 year, 1-5 years, and >5 years after diagnosis of IgG4-SC were 2.58, 1.01, and 2.44, respectively. CONCLUSIONS: IgG4-SC patients have a high risk of cancer including pancreatic and bile duct cancer. The risk of cancer was high less <1 year and >5 years after diagnosis of IgG4-SC. Therefore, IgG4-SC patients may require careful long-term follow-up.

Percent reduction of the ulcer size at 4 weeks is a predictor of the complete healing of endoscopic submucosal dissection-induced gastric ulcers.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is widely used as a treatment modality for gastric mucosal neoplasia. While proton pump inhibitors (PPIs) have been used for the control of artificial ulcers created by ESD (ESD-ulcers), complete healing of the ulcers is not always achieved in all the cases. The purpose of this study was to identify the clinical factors that are predictive of refractory ESD-ulcers. PATIENTS AND METHODS: We recruited 90 patients with 102 artificial ulcers that formed after the patients underwent ESD for gastric tumours. All the patients received a 20-mg capsule of esomeprazole daily until the 56th day after ESD, and underwent endoscopy at 1, 4, 6 and 8 weeks after the ESD. We analyzed the clinical factors that were associated with the complete healing at 8 weeks after the ESD (CH-8w). The ulcers in the scar stage were defined as the complete healing in this study. RESULTS: Of the 102 ESD-ulcers, 16.7% failed to show complete healing after the 8 weeks of PPI therapy. Univariate analysis identified the percent reduction of the ulcer size at 4 weeks after ESD (PR-4w) as being significantly associated with CH-8w. Multivariate analysis identified ulcer location in the lower-third of the stomach and PR-4w > 95% as being independently correlated with the CH-8w (odds ratio = 4.86 and 7.89, respectively). Analysis of the area under the receiver operating characteristic (AUROC) curve demonstrated that the AUROC curve of PR-4w for predicting the CH-8w was 0.78. CONCLUSION: Based on the results of our study, endoscopic observation at 4 weeks after ESD would help in the early identification of refractory ESD-ulcers.

Effect of vonoprazan on the treatment of artificial gastric ulcers after endoscopic submucosal dissection: Prospective randomized controlled trial.

BACKGROUND AND AIM: Proton pump inhibitors are effective for the treatment of gastric ulcers after endoscopic submucosal dissection (ESD). However, the most excellent therapy is controversial. Vonoprazan, an active potassium-competitive acid blocker, has a strong gastric acid secretion inhibitory effect, but its efficacy for the treatment of post-ESD gastric ulcers is unclear. Herein, we aimed to determine the healing effect of vonoprazan on post-ESD gastric ulcers. METHODS: We carried out a prospective randomized controlled trial examining 92 patients who had undergone ESD for the treatment of gastric neoplasms between April 2015 and June 2016 at Machida Municipal Hospital. Patients were treated with 20 mg/day vonoprazan (V group) or 20 mg/day esomeprazole (E group) for 8 weeks. We evaluated the 8-week cure rate for artificial ulcers and any complications after ESD. RESULTS: A total of 80 patients (median age, 73.5 years; 71.3% male) were analyzed. Cure rate for the V group was significantly higher than that for the E group (94.9% [37/39] vs 78.0% [32/41], respectively; P = 0.049). In a multivariate analysis, only vonoprazan was correlated with ulcer healing (odds ratio = 6.33; 95% CI = 1.21-33.20; P = 0.029). Delayed bleeding was experienced only in the E group (7.3% [3/41]), but no significant difference compared with the V group was observed (P = 0.241). CONCLUSION: Vonoprazan was significantly superior to esomeprazole for the healing of post-ESD gastric ulcers and should be considered as a treatment of first choice.

Association between the location of diverticular disease and the irritable bowel syndrome: a multicenter study in Japan.

OBJECTIVES: No previous reports have shown an association between location of diverticular disease (DD) and the irritable bowel syndrome (IBS). METHODS: We included 1,009 consecutive patients undergoing total colonoscopy in seven centers in Japan from June 2013 to September 2013. IBS was diagnosed using Rome III criteria, and diverticulosis was diagnosed by colonoscopy with transparent soft-short-hood. Left-sided colon was defined as sigmoid colon, descending colon, and rectum. Right-sided colon was defined as cecum, ascending colon, and transverse colon. We divided the patients into IBS and non-IBS groups and compared characteristics. RESULTS: Patient characteristics included mean age, 64.2±12.9 years and male:female ratio, 1.62:1. Right-sided DD was identified in 21.6% of subjects. Left-sided and bilateral DD was identified in 6.6 and 12.0% of subjects, respectively. IBS was observed in 7.5% of subjects. Multiple logistic regression analysis showed left-sided DD (odds ratio, 3.1; 95% confidence interval (CI): 1.4-7.1; P=0.0060) and bilateral DD (odds ratio, 2.6; 95% CI, 1.3-5.2; P=0.0070) were independent risk factors for IBS. Right-sided DD was not a risk factor for IBS. CONCLUSIONS: Our data showed that the presence of left-sided and bilateral DD, but not right-sided disease, was associated with a higher risk of IBS, indicating that differences in pathological factors caused by the location of the DD are important in the development of IBS. Clarifying the specific changes associated with left-sided DD could provide a better understanding of the pathogenic mechanisms of IBS (Trial registration # R000012739).

Autoimmune pancreatitis associated with pancreatic cyst: how can we manage it?

BACKGROUND: Autoimmune pancreatitis (AIP) with cyst formation (ACF) is often refractory to corticosteroid treatment (CST). AIM: To determine the characteristic features for the development of ACF. METHODS: We studied characteristics in AIP patients (n = 116) whether any factors might be related to ACF. Additionally, an individual database of 24 patients was compiled to investigate factors included CST effectiveness. RESULT: The results of univariate analysis for type 1 AIP patients revealed significant association of ACF with the elevation of pancreatic enzymes, peripancreas vascular involvement (PVI) and varix formation at disease onset (P < 0.05), while multivariate analysis revealed only the absence of varix formation (odds ratio = 0.033, P = 0.0015) as a significant independent predictor of the development of ACF. The comparison of the characteristic features in ACF grouped by the diameter of the cysts revealed that only the effectiveness of the CST was significantly recognized in ACF measuring less than 55 mm in diameter than that with patients in the group with smaller cysts (P < 0.05). CONCLUSION: The varix formation is an independent predictor of the development of ACF. A pooled analysis indicated that the disease process might be irreversible in AIP patients with large cystic lesions exceeding 55 mm in diameter and those patients tended to show a refractory course even if CST were conducted.

[Disseminated varicella-zoster virus infection complicated with severe abdominal pain and colonic pseudo-obstruction].

A 48-year-old man was admitted to our hospital complaining of acute severe abdominal pain and constipation. He had received bone marrow transplantation for acute myelogenous leukemia 5 months previously and immunosuppressant treatment for chronic graft-versus-host disease. Abdominal X-ray and CT scan films revealed his large intestine widely dilated and filled with air, and colonic pseudo-obstruction was diagnosed. It was difficult to ascertain the cause of the symptoms until 6 days after onset of the abdominal pain when disseminated zoster eruption appeared over his whole body. It was disseminated varicella-zoster and complicated with colonic pseudo-obstruction. He was treated with acyclovir. It is important to suspect disseminated varicella-zoster and treat early immunocompromised patients complaining of severe acute abdominal pain and colonic pseudo-obstruction.

Risk factors for colonic diverticular hemorrhage: Japanese multicenter study.

BACKGROUND AND AIM: Diverticular hemorrhage is the common cause of lower gastrointestinal bleeding, and its incidence has been increasing in Japan. However, the exact cause of diverticular hemorrhage is not well understood. We investigated the risk factors for diverticular hemorrhage. METHODS: We selected 103 patients with diverticular hemorrhage as cases and patients with colonic diverticulosis without a history of bleeding were selected as control subjects, exactly matched for age and gender. We collected the data from the medical records of each of the patients, such as those related to the comorbidities, medications and findings of colonoscopy, and conducted a matched case-control study to analyze the risk factors for diverticular hemorrhage. RESULTS: Both groups were composed of 75 men and 28 women. The median age of the patients in both groups was 72.0 years (47.0-87.0). The body weight (p = 0.0065), body mass index (p = 0.006), prevalence of hypertension (p = 0.0242), prevalence of ischemic heart disease (p = 0.0015), and frequency of use of low-dose aspirin (p = 0.042) were significantly different between the two groups. The percentage of patients with bilateral diverticula, that is, diverticula on both the right and left hemicolon, was significantly higher in the diverticular hemorrhage group (p = 0.0011). Multiple regression analysis identified only the diverticular location as being significantly associated with the risk of diverticular hemorrhage (p = 0.0021). CONCLUSIONS: Only the diverticular location (bilateral) was found to be an independent risk factor for diverticular hemorrhage.

Neurite outgrowth of PC12 mutant cells induced by orange oil and d-limonene via the p38 MAPK pathway.

We studied the effects of natural essential oil on neurite outgrowth in PC12m3 neuronal cells to elucidate the mechanism underlying the action of the oils used in aromatherapy. Neurite outgrowth can be induced by nerve growth factor (NGF), where ERK and p38 MAPK among MAPK pathways play important roles in activating intracellular signal transduction. In this study, we investigated whether d-limonene, the major component of essential oils from oranges, can promote neurite outgrowth in PC12m3 cells, in which neurite outgrowth can be induced by various physical stimulations. We also examined by which pathways, the ERK, p38 MAPK or JNK pathway, d-limonene acts on PC12m3 cells. Our results showed that neurite outgrowth can be induced when the cells are treated with d-limonene. After treatment with d-limonene, we observed that p38 MAPK is strongly activated in PC12m3 cells, while ERK is weakly activated. In contrast, JNK shows little activity. A study using an inhibitor of p38 MAPK revealed that neurite outgrowth in PC12m3 cells is induced via the activation of p38 MAPK by d-limonene. The results thus indicate that d-limonene may promote neural cell differentiation mainly via activation of the p38 MAPK pathway.

Incidence of and risk factors for upper gastrointestinal complications in patients taking low-dose aspirin in Japan.

BACKGROUND/AIMS: Low-dose aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases. However, administration of low-dose aspirin is associated with an increased risk of upper gastrointestinal complications, such as upper gastrointestinal erosions, ulcers and bleeding. The aim of this study was to clarify the prevalence and various clinical factors of upper gastrointestinal complications associated with low-dose aspirin treatment. METHODOLOGY: A total of 1213 patients taking low-dose aspirin were evaluated with upper endoscopic examinations. We studied retrospectively the incidence of and risk factors for upper gastrointestinal complications associated with low-dose aspirin use. RESULTS: Of the 1213 patients taking low-dose aspirin, 598 patients and 72 patients were found to have gastroduodenal erosions (57.3%) and peptic ulcers (5.9%), respectively. Of these 72 peptic ulcers, 27 were diagnosed as hemorrhagic ulcers. Previous ulcer history was identified as a risk factor for peptic ulcer and upper gastrointestinal bleeding during low-dose aspirin therapy. Upper gastrointestinal symptoms and no use of gastroprotective agents were also identified as risk factors for peptic ulcers. In this study, the use of a histamine-2 receptor antagonist was indicated as a protective factor for peptic ulcers. CONCLUSIONS: Low-dose aspirin therapy is associated with an increased risk of developing upper gastrointestinal complications. Administration of a histamine-2 receptor antagonist was effective for the prevention of low-dose aspirin induced peptic ulcers.

Factors predictive of relapse and spontaneous remission of autoimmune pancreatitis patients treated/not treated with corticosteroids.

BACKGROUND: Relapse and spontaneous remission (SR) are characteristic features of autoimmune pancreatitis (AIP). AIM AND METHODS: We conducted a study to determine if the predictive factors might be potentially related to the relapse in 70 consecutive AIP patients. Regarding SR, we studied the data of patients without corticosteroid treatment (CST). RESULTS: CST was administered to 60% (42/70) of the patients; however, relapse was noted in 45.2% (19/42) of these patients. In 95% (18/19) of the AIP patients developing relapse, the relapse occurred within 3 years. The relapse rate was 80% (12/15) in the AIP patients administered CST for less than 12 months and 25.9% (7/27) in those administered CST for over 12 months (p < 0.01). The results of univariate analysis revealed significant association of relapse with the presence of jaundice, IgG4 seropositivity, presence of diffuse pancreas swelling, duodenal papillitis (DP), history of initial CST, and history of supportive treatment (p < 0.05), whereas multivariate analysis revealed that IgG4 seropositivity (OR 10.506, p = 0.0422) and the presence of jaundice (OR 6.945, p = 0.0174) are significant independent factors predictive of relapse in AIP patients. SR was recognized in 65.0% (13/20) of AIP patients without CST. The results of univariate analysis revealed that SR was associated with IgG4 seropositivity (p < 0.05), and multivariate analysis identified IgG4 seropositivity (OR 0.032, p = 0.0092) as a significant independent factor predictive of SR in these cases. CONCLUSION: AIP patients with IgG4 seropositivity and jaundice are at a higher risk of relapse and they could therefore be candidates for over 3 years of maintenance CST. AIP patients with IgG4 seronegativity have a high likelihood of SR.