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.

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.

Efficacy and safety of colorectal endoscopic submucosal dissection in patients with sarcopenia.

BACKGROUND: Endoscopic submucosal dissection (ESD) for early-stage colorectal cancer (CRC) has become a common and useful treatment. Although sarcopenia has been identified as an independent risk factor for complications after surgery for CRC, whether sarcopenia is also an independent risk factor for complications after colorectal ESD remains to be clarified. The aim of this study was to compare the outcomes of colorectal ESD in patients with and those without sarcopenia. METHODS: This is a retrospective cohort study. A total of 334 patients underwent colorectal ESD for 361 neoplasms at Hiratsuka City Hospital from March 2012 to October 2018. The neoplasms were divided into two groups depending on the presence or absence of sarcopenia in the patients. RESULTS: Overall, 334 patients underwent colorectal ESD for 361 neoplasms during the study period. We excluded 90 patients (90 neoplasms), and 244 patients (277 neoplasms) were included in the final analysis (134 from the sarcopenia group, 137 from the non-sarcopenia group). The en-bloc resection rate was high and was not significantly different between the sarcopenia group [126/134 (94.1%)] and the non-sarcopenia group [133/137 (97.1%)], P = 0.1778). The rate of perforation and the rate of delayed bleeding were not significantly different between the sarcopenia group and the non-sarcopenia group [6/134 (4.5%) vs. 9/137 (6.6%), P = 0.314, 4/134 (3%) vs. 6/137 (4.4%), P = 0.3885, respectively]. CONCLUSIONS: The presence of sarcopenia did not influence the rate of complications after ESD. Colorectal ESD is safe and effective even in patients with sarcopenia. Prospective multicenter studies are necessary to confirm our results.

The placement of multiple plastic stents still has important roles in candidates for chemotherapy for unresectable perihilar cholangiocarcinoma.

BACKGROUND/PURPOSE: Placement of uncovered self-expandable metallic stents (U-SEMSs) of patients with unresectable perihilar cholangiocarcinoma (UPHC) is recommended as the treatment of first choice to address bile stasis. The aim of this study was to determine which of the following two endoscopic stents might be the stent of first choice for the treatment of biliary stasis in patients with UPHC: plastic stents (PSs) or U-SEMSs. METHODS: U-SEMSs, deployed as a stent-in-stent, were selected as the stents of first choice from 2013 and 2014, while PSs began to be selected as the stents of first choice from 2015 onward. RESULTS: The median time to recurrent biliary obstruction were 66 days in the PS group (N = 38) and 105 days in the U-SEMS group (N = 37; P = .04). Emergency endoscopy was necessitated in 76.3% (29/38) of patients of the PS group and 54.1% (20/37) of patients of the U-SEMS group (P = .0434). The success rate of the first reintervention was 96.5% (27/29) in the PS group and 55% (11/20) in the U-SEMS group (P = .0002). Sustainable chemotherapy could be carried out in 55.2% of patients in the PS group and 32.4% of patients in the U-SEMS group (P = .0472). Multivariate analysis identified selection of U-SEMS as the stent of first choice as the only independent factor predictive of successful reintervention (P = .0016, odds ratio = 0.058). However, the stent selection was not an independent factor for feasible chemotherapy. CONCLUSIONS: Plastic stent placement could enhance the success rate of reintervention in patients with UPHC and might be facilitated by sustainable chemotherapy. However, stent selection might not have an influence on the prognosis.

Effect of preventive closure of the frenulum after endoscopic papillectomy: A prospective pilot study.

BACKGROUND AND AIM: The usefulness of preventive closure of the frenulum after endoscopic papillectomy (EP) could reduce bleeding. The feasibility and safety of clipping were evaluated in this prospective pilot study. METHODS: This study involved 40 consecutive patients who underwent preventive closure of the frenulum by clipping just after EP. The outcome data were compared with those of the previous 40 patients in whom no preemptive closure had been performed (no-closure group) (UMIN000014783). Additionally, the bleeding sites were examined. RESULTS: The clipping procedure was successful in all patients. As compared to the no-closure group, the rate of bleeding (P = 0.026) and period of hospital stay (P < 0.001) were significantly reduced in the closure group. There was no difference in the procedure time between the two groups. Furthermore, the incidence rates of pancreatitis and perforation were comparable in the two groups. The bleeding was noted in the frenulum area rather than at any other site in 90.9% of cases. CONCLUSION: Preventive closure of the frenulum after EP is an effective, safe, rational, and economical method to reduce the incidence of delayed bleeding, without prolonging the procedure time or increasing the risk of post-procedure pancreatitis perforation.

Three-dimensional analysis of pancreatic fat by fat-water magnetic resonance imaging provides detailed characterization of pancreatic steatosis with improved reproducibility.

BACKGROUND: Since pancreatic steatosis is reported as a possible risk factor for pancreatic cancer, the development of a non-invasive method to quantify pancreatic steatosis is needed. Proton density fat fraction (PDFF) measurement is a magnetic resonance imaging (MRI) based method for quantitatively assessing the steatosis of a region of interest (ROI). Although it is commonly used for quantification of hepatic steatosis, pancreatic PDFF can greatly vary depending on the ROI's location because of the patchy nature of pancreatic fat accumulation. In this study, we attempted to quantify pancreatic steatosis by fat-water MRI with improved reproducibility. METHODS: Using the MRI images of 159 patients with nonalcoholic fatty liver disease, we attempted to calculate the average PDFF of whole pancreas. We set ROIs covering the entire area of the pancreas appearing in every slice and calculated the average PDFF from all the voxels included in the pancreas. We named this average value as whole-pancreatic PDFF and evaluated the reproducibility of the measured values. In addition to whole-pancreatic PDFF, we measured the average PDFF of the pancreatic head (head-PDFF) and that of the pancreatic body plus tail separately and analyzed their correlation with the clinical characteristics of the patients. RESULTS: The mean inter-examiner coefficient of variation of the whole-pancreatic PDFF was 11.39%. The whole-pancreatic PDFF was correlated with age (p = 0.039), body mass index (p = 0.0093) and presence/absence of diabetes (p = 0.0055). The serum level of low-density lipoprotein cholesterol was inversely correlated with the head-PDFF. CONCLUSION: We developed a new measurement method of the pancreatic PDFF with greater reproducibility. Using this method, we characterized pancreatic steatosis in detail. This novel measurement method allows accurate estimation of the severity of pancreatic steatosis and is therefore useful for the detailed characterization of pancreatic steatosis.

Clinical features of isolated proximal-type immunoglobulin G4-related sclerosing cholangitis.

BACKGROUND AND AIM: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) presents as isolated proximal-type sclerosing cholangitis (i-SC). The present study sought to clarify the imaging differences between i-SC and Klatskin tumor. Differences between i-SC and IgG4-SC associated with autoimmune pancreatitis (AIP-SC) were also studied. METHODS: Differentiating factors between i-SC and Klatskin tumor were studied. Serum IgG4 level, CA19-9 level, computed tomography (CT) findings, cholangiography findings (symmetrical smooth long stricture extending into the upper bile duct [SSLS]), endosonographic features (continuous symmetrical mucosal lesion to the hilar part [CSML]), endoscopic biopsy results, treatment, relapse, and survival were also compared between patients with i-SC and those with AIP-SC. RESULTS: For a differential diagnosis between i-SC (N = 9) and Klatskin tumor (N = 47), the cut-off value of serum IgG4 level was 150 mg/dL (sensitivity, 0.857, specificity, 0.966). Logistic regression analysis indicated that serum IgG4 level, presence of SSLS, presence of CSML, and presence of swollen ampulla are independent factor for identifying i-SC. Relapse rate was significantly higher in the IgG4-SC with AIP group than in the i-SC group (log rank, P = 0.046). CONCLUSION: Isolated proximal-type sclerosing cholangitis presents as a nodular lesion with SSLS and/or CSML mimicking a Klatskin tumor. Those endoscopic features might provide a diagnostic clue for i-SC. i-SC is likely to have a more favorable prognosis than IgG4-SC with AIP.

Lubiprostone improves intestinal permeability in humans, a novel therapy for the leaky gut: A prospective randomized pilot study in healthy volunteers.

BACKGROUND AND AIMS: The barrier function of the small intestinal mucosa prevents the introduction of undesired pathogens into the body. Breakdown of this barrier function increases intestinal permeability. This has been proposed to induce not only gastrointestinal diseases, including inflammatory bowel disease and irritable bowel syndrome, but also various other diseases, including allergies, diabetes mellitus, liver diseases, and collagen diseases, which are associated with this so called "leaky gut syndrome." As such, a method to prevent leaky gut syndrome would have substantial clinical value. However, no drugs have been demonstrated to improve disturbed intestinal permeability in humans to date. Therefore, we investigated whether a drug used to treat chronic constipation, lubiprostone, was effective for this purpose. METHODS: Healthy male volunteers were treated with lubiprostone (24 µg/day) for 28 days. Intestinal permeability was evaluated by measuring the lactulose-mannitol ratio (LMR) after administration of diclofenac and compared with an untreated group. The examination was conducted three times in total, i.e., at baseline before diclofenac administration and after 14 and 28 days of lubiprostone treatment. Blood endotoxin activity was also evaluated at the same time points. RESULTS: The final analysis was conducted on 28 subjects (14 in the lubiprostone group and 14 in the untreated group). The LMR after 28 days of treatment was significantly lower in the lubiprostone group than that in the untreated group (0.017 vs. 0.028, respectively; 95% confidence interval, -0.022--0.0001; p = 0.049). Blood endotoxin activity exhibited almost no change over time in the lubiprostone and untreated groups and displayed no significant differences at any time point of examination. CONCLUSIONS: This study is the first to report an improvement in leaky gut using an available drug in humans. The result suggests that lubiprostone may prevent and ameliorate "leaky gut syndrome". However, a pivotal trial is needed to confirm our finding.

Feasibility of Endoscopic Papillary Large Balloon Dilation in Patients with Difficult Bile Duct Stones without Dilatation of the Lower Part of the Extrahepatic Bile Duct.

BACKGROUND/AIMS: There is no consensus for using endoscopic papillary large balloon dilation (EPLBD) in patients without dilatation of the lower part of the bile duct (DLBD). We evaluated the feasibility and safety of EPLBD for the removal of difficult bile duct stones (diameter ≥10 mm) in patients without DLBD. METHODS: We retrospectively reviewed the records of 209 patients who underwent EPLBD for the removal of bile duct stones from October 2009 to July 2014. Primary outcomes were the clearance rate and additional mechanical lithotripsy. Secondary outcomes were the incidence of complications and recurrence rate. RESULTS: Fiftyseven patients had DLBD (27.3%), and 152 did not have DLBD (72.7%). There were no significant differences in the overall success rate or the use of mechanical lithotripsy. Success rate during the first session and procedure time were better in the DLBD than the without-DLBD group (75.7% vs 66.7%, 48.1±23.0 minutes vs 58.4±31.7 minutes, respectively). As for complications, there were no significant differences in the incidence of pancreatitis, perforation or bleeding after endoscopic retrograde cholangiopancreatography. The recurrence rate did not differ significantly between the two groups. CONCLUSIONS: EPLBD is a useful and safe method for common bile duct stone removal in patients without DLBD.

Intravenous injection of low-dose flurbiprofen axetil for preventing post-ERCP pancreatitis in high-risk patients: An interim analysis of the trial.

Background and study aims: Several meta-analyses and randomized control trials have demonstrated the efficacy of rectal nonsteroidal anti-inflammatory drugs for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). Diclofenac or indomethacin was administered at a dose of 100 mg in those studies, which may be too high for Asian population. In addition, rectal administration can be considered complicated. Patients and methods: This study was a prospective, randomized, placebo-controlled trial. Patients with a PEP risk score ≥ 1 were randomly assigned to receive intravenous injection of 50 mg flurbiprofen axetil (flurbiprofen group) or saline only (placebo group). The primary outcome was reduced PEP. The secondary outcome was amylase level after 2 hours of ERCP as a predictor of PEP. (Clinical Trials.gov, ID UMIN000011322) Results: In total, 144 patients were enrolled from August 2013 to March 2015. We performed an interim analysis of the first 100 patients: 47 received flurbiprofen axetil and 53 received placebo. PEP occurred in 11 patients (11 %): 2 of 47 (4.3 %) in the flurbiprofen group and 9 of 53 (17 %) in the placebo group (P = 0.042). Relative risk reduction was 62.4 %. Hyperamylasemia did not differ significantly (17.0 % vs. 26.4 %, P = 0.109). This analysis resulted in early termination of the study for ethical reasons. Conclusions: Intravenous injection of low-dose flurbiprofen axetil after ERCP can reduce the incidence of PEP in high-risk patients.

Stent placement above the sphincter of Oddi permits implementation of neoadjuvant chemotherapy in patients with initially unresectable Klatskin tumor.

BACKGROUND AND STUDY AIMS: Neoadjuvant chemotherapy (NAC) may lead to a successful margin-negative resection in patients with initially unresectable locally advanced Klatskin tumor (IULAKT). Use of removable plastic stents is preferable for the safe implementation of NAC in patients with IULAKT to reduce the risk of recurrent cholangitis. Our aim was to evaluate the efficacy associated with the use of plastic stents placed across the stenosis and above the papilla (above stent) during NAC. PATIENTS AND METHODS: In this study, we stratified the patients into two groups chronologically with respect to the period of stent placement: above stent group (n = 17) and across stent group (n = 23) (plastic stent across the sphincter of Oddi). RESULTS: The median stent patency period was 99 days in the above stent group and 31 days in the across stent group (P < 0.0001). The number of stents (P = 0.017) and the rate of emerging undrained cholangitis areas (P = 0.025) were significantly reduced in the above stent group than the counterpart. Regarding time to recurrent biliary obstruction, the above stent group had a longer duration than the across stent group (log rank test, P = 0.004). Length of hospital stay was significantly shorter for the above stent group than the across stent group (P = 0.0475). Multivariate analysis revealed that above stent placement (odds ratio = 33.638, P = 0.0048) was significantly associated with stent patency over a period of 90 days. CONCLUSIONS: Above stent placement should be considered for the relief of biliary obstruction and potentially reduces the cost for patients with IULAKT scheduled to receive NAC.

Electronic structure of disjoint diradical 4,4'-bis(1,2,3,5-dithiadiazolyl) thin films.

The electronic structure of the thiazyl diradical, 4,4'-bis(1,2,3,5-dithiadiazolyl) (BDTDA), has been investigated by ultraviolet photoemission spectroscopy. Stacked BDTDA dimers showed an energy band dispersion of about 0.3 eV for the highest occupied molecular orbital in the direction of the surface normal of the BDTDA solid film. The pi-orbital overlap between the stacked dimers therefore evolves into a quasi one-dimensional energy band along the dimer stacking direction.

Interactive radical dimers in photoconductive organic thin films.

Fully interactive: Overlap between extended unoccupied molecular orbitals leads to the high photoconductivity of interactive radical dimers. Sandwich-type cells (see picture; ITO = indium tin oxide) comprising highly oriented thin films of a disjoint diradical, 4,4'-bis(1,2,3,5-dithiadiazolyl) (BDTDA) exhibit a photocurrent with a high on/off ratio at reverse bias voltages and photovoltaic behavior at zero bias voltage.