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Predictive factors for intrahepatic cholangiocarcinoma in long-term follow-up of hepatolithiasis are unknown. We thus conducted a cohort study to investigate the predictive factors for developing intrahepatic cholangiocarcinoma in hepatolithiasis.This cohort is comprised of 401 patients registered in a nationwide survey of hepatolithiasis for 18 years of follow-up. Cox regression analysis was used to elucidate predictive factors for developing intrahepatic cholangiocarcinoma.The median follow-up period of patients was 134 months. Twenty-two patients developed intrahepatic cholangiocarcinoma and all died. Identified independent significant factors were as follows: age 63 years or older (hazard ratio [HR] 3.344), residual stones at the end of treatment (HR 2.445), and biliary stricture during follow-up (HR 4.350). The incidence of intrahepatic cholangiocarcinoma in patients with three factors was significantly higher than that in patients with one or two factors. The incidence in the groups with one or two predictive factors was not different. In 88.9% of patients with both biliary stricture and intrahepatic cholangiocarcinoma, the duration between the diagnoses of biliary stricture and intrahepatic cholangiocarcinoma was ≥ 5 years. However, once intrahepatic cholangiocarcinoma developed, 77.8% of patients died within 1 year. Of 24 patients with no symptoms, no previous choledocoenterostomy, no signs of malignancy, no biliary stricture, and no treatment for hepatolithiasis during follow-up, only one developed intrahepatic cholangiocarcinoma.Regarding carcinogenesis, complete stone clearance and releasing biliary stricture can prevent the development of intrahepatic cholangiocarcinoma and improve the prognosis of hepatolithiasis.

The role of a covered vs. an uncovered self-expandable metal stent (SEMS) for malignant distal biliary obstruction (MDBO) is not clear. This meta-analysis compared the efficacy of covered vs. uncovered SEMS for patients with MDBO after endoscopic insertion.A systematic meta-analysis of all relevant articles listed in PubMed, the Cochrane Library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled effects with 95% confidence intervals (CIs).The meta-analysis included 2358 patients from 12 eligible studies. Time to recurrent biliary obstruction (RBO) was significantly longer for covered SEMS (mean difference, 45.51 days; 95% CI 11.79-79.24). Although there was no significant difference in the RBO rate, subgroup analysis in pancreatic cancer occupying more than 90% (PC) revealed that the RBO rates were significantly lower for covered SEMS (odds ratio [OR] 0.43, 95% CI 0.25-0.74). Stent migration, sludge formation, and overgrowth were significantly more common with a covered SEMS (OR 7.92, 95% CI 4.01-15.64; OR 3.25, 95% CI 1.89-5.59; OR 2.03, 95% CI 1.20-3.43, respectively). The rate of ingrowth was significantly lower for covered SEMS. There was no significant difference in total procedure-related adverse events between the two types of SEMS.A covered SEMS is superior to an uncovered SEMS with respect to prevention of RBO in patients with MDBO, particularly those caused by PC.

Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy (EUS-PGS) is a useful alternative when endoscopic retrograde pancreatography is difficult. Recently, many procedures, including peroral pancreatoscopy (POPS), have been performed through the mature fistula (MF) created by EUS-PGS. We evaluate the efficacy and safety of POPS to diagnose and treat pancreatic ductal stricture/pancreato-jejunal anastomotic stricture (PDS/PJAS) through the MF.Twenty patients underwent EUS-PGS; 13 of these underwent POPS through the MF at Juntendo University Hospital. All patients were studied retrospectively in terms of technical and clinical success rates and adverse events (AEs).The technical and clinical success rates of EUS-PGS were 95% and 100%. The early and late AEs rates were 20% and 15%. The technical success rate of POPS was 100%, with one AE. Biopsy of PDS/PJAS under POPS guidance revealed recurrent/residual intrapapillary mucinous adenoma (3 patients) and benign fibrotic stricture (10 patients). In the latter patients, multiple plastic stents were placed to dilate PDS/PJAS. Four patients with improvement of PDS/PJAS were stent free, but the remaining patients were not yet.Endoscopic ultrasound/endosonography-guided pancreaticogastrostomy and various procedures (including POPS) performed through the MF are feasible and effective and can diagnose and treat PDS/PJAS with acceptable AEs rates.

BACKGROUND/PURPOSE Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. METHODS We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels ("strong", "medium", "weak", "very weak"). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. RESULTS These guidelines address 3 subjects: diagnostic, chemotherapeutic, and surgical approaches. They include 9 clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one "column". CONCLUSIONS This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

Background Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. Methods The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. Results Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. Conclusion Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.

Background Several serious complications are associated with the lithotomy position, including well-leg compartment syndrome and peroneal nerve paralysis. The aims of this study were to identify risk factors for the intraoperative elevation of lower leg pressure and to evaluate the effectiveness of monitoring external pressure during surgery for preventing these complications. Methods The study included 106 patients with a diagnosis of sigmoid colon or rectal cancer who underwent elective laparoscopic surgery between June 2019 and December 2020. We divided the posterior side of the lower leg into four parts (upper outside, upper inside, lower outside, lower inside) and recorded the peak pressure applied to each area at hourly intervals during surgery (called "regular points") and when the operating position was changed (e.g., by head-tilt or leg elevation; called "points after change in position"). When the pressure was observed to be higher than 50 mmHg, we adjusted the position of the leg and re-recorded the data. Data on postoperative leg-associated complications were also collected. Results The pressure was measured at a total of 1125 points (regular, n = 620; after change of position, n = 505). The external pressure on the upper outer side of the right leg (median, 36 mmHg) was higher than that on any other area of the lower leg. The pressure increase to more than 50 mmHg was observed not only during the change of position (27.5%) but also during regular points (22.4%). Bodyweight, strong leg elevation, and low head position were identified as factors associated with increased external pressure. There have been no compression-related complications in 534 cases at our institution since the introduction of intraoperative pressure monitoring. Conclusions Several risk factors associated with increased external pressure on the lower leg were identified. Intraoperative pressure monitoring might help reduction of pressure-related complications, needing further and larger prospective data collections.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is associated with a poor prognosis with variable clinical course. Early identification of patients at high risk for disease progression and death would lead to early therapeutic intervention and thereby improvement of outcomes. Cold-inducible RNA-binding protein (CIRBP) is produced in response to cellular stresses, which is implicated in multiple biological processes, including cell survival and proliferation.RESEARCH QUESTION: Is CIRBP a useful biomarker for predicting the outcomes of patients with IPF?STUDY DESIGN AND METHODS: This study included 95 and 93 patients with IPF from two independent hospitals (derivation and validation cohorts, respectively). The association s of serum CIRBP level upon IPF diagnosis with disease progression within 1 year after diagnosis (i.e. ≥10% relative decline in percent predicted forced vital capacity or death) and all-cause mortality were retrospectively analysed. Discrimination performances for predicting these outcomes were evaluated using the c-index. RESULTS: Serum and lung tissue CIRBP levels were higher in patients with IPF than in control subjects. In the derivation cohort, the CIRBP high sub-group had significantly higher 1-year disease progression rates and lower cumulative survival rates than the CIRBP low sub-group, and the results were replicated in the validation cohort. In multivariate analyses, high serum CIRBP level was independently associated with higher 1-year disease progression and all-cause mortality rates in both cohorts. Combining the Gender-Age-Physiology and serum CIRBP models improved the c-indices for predicting 1-year disease progression and all-cause mortality compared with that of each model alone. The c-indices of serum CIRBP were particularly high in patients with Gender-Age-Physiology stage I.INTERPRETATION: This study successfully validated that serum CIRBP level was an independent predictor of 1-year disease progression and all-cause mortality in IPF. CIRBP is a promising biomarker that can help identify high-risk patients with IPF, especially in the early stage.

AIM Anti-ribosomal P protein antibodies (anti-ribo P) have been reported as one of the specific autoantibodies in patients with systemic lupus erythematosus (SLE) and has been demonstrated to bind and activate macrophages in vitro. Clinically, hyperferritinemia has been known to be a biomarker for macrophage activation. The aim of this study is to clarify the relationship of anti-ribo P and clinical characteristics and biomarkers including serum ferritin in patients with SLE. METHODS Clinical parameters and laboratory data were measured in patients with active SLE (N = 127) in our university hospital. The risk factors affected by anti-ribo P were retrospectively calculated by logistic regression analysis, and the correlation of anti-ribo P and clinical factors was demonstrated. RESULTS Anti-ribo P was significantly elevated in active SLE compared to non-SLE diseases (P

Background Pressure ulcers are the most common complications in bedridden patients or those with spinal cord injuries. Marjolin's ulcer refers to a malignant transformation arising from burn scars or chronic nonhealing wounds—such as pressure ulcers—over many years. Squamous cell carcinoma is the major histopathologic type of Marjolin's ulcer, and the gold standard for diagnosis is tissue biopsy. Medical professionals may have difficulty distinguishing pressure ulcers from Marjolin's ulcer, especially when the latter presents with invasive infections. Thus, malignant transformations arising from pressure ulcers are frequently overlooked. Herein, we describe a case of squamous cell carcinoma arising from pressure ulcers on the left ischium, which was initially identified as a necrotizing soft tissue infection. Case report A 59-year-old paraplegic patient presented with stage 3 left ischial pressure ulcer, which involves full-thickness skin loss and extends into deep subcutaneous tissue, and arrived at our hospital with suspected sepsis. Upon physical examination, the patient presented with fever and shivering. Initial examination and imaging findings revealed the presence of necrotizing soft tissue infections. Three weeks later, rapid increase in granulation in the deep part of the ulcer was observed. Samples from multiples ulcer sites were collected for tissue biopsy. Finally, histological examination revealed well-differentiated squamous cell carcinoma. The patient received radiation therapy and chemotherapy and died 11 months after the diagnosis. Conclusion Malignant transformations arising from pressure ulcers may closely resemble pressure ulcer infections. In these cases, tissue biopsies should be performed during primary care for the infection to exclude malignant transformations.

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.Methods: Thirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.Results: The serum levels of S100A8 (median 386.5ng/mL) and S100A9 (median 60.2ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p

BACKGROUND Disconnected pancreatic duct syndrome (DPDS) frequently occurs in patients with acute necrotizing pancreatitis and resultant pancreatic fluid collection (PFC). We performed a systematic review and meta-analysis to evaluate outcomes of endoscopic ultrasound-guided treatment of PFCs according to the presence of DPDS. METHODS Using PubMed, Embase, and the Cochrane database, we identified clinical studies published until January 2021 with data comparing outcomes of endoscopic ultrasound-guided drainage of PFCs between DPDS and non-DPDS patients. We pooled data on technical and clinical success rates, PFC recurrence, and adverse events using the random-effects model. RESULTS We identified five eligible articles including 941 PFC patients treated with endoscopic ultrasound-guided interventions. Clinical success, defined as resolution of the PFC and symptoms, was achieved in a majority of the cases irrespective of DPDS (pooled odds ratio [OR] comparing DPDS to non-DPDS patients, 0.77; 95% confidence interval [CI] 0.33-1.81). Compared to patients without DPDS, patients with DPDS were more likely to undergo PFC recurrence (pooled OR 6.72; 95% CI 2.72-16.6) after clinical resolution of PFC. Prolonged plastic stent placement following the clinical resolution was more frequently performed in DPDS patients than in non-DPDS patients (pooled OR 15.9; 95% CI 2.76-91.9). No statistically significant difference was observed between the groups in terms of the rate of technical success, adverse events, or mortality. CONCLUSION Disconnected pancreatic duct syndrome was associated with higher rate of PFC recurrence after successful endoscopic treatment of PFCs. Future studies should evaluate effectiveness and optimal duration of long-term placement of transmural plastic stents for PFCs with DPDS.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Objectives The oncological outcomes, especially high recurrence rate, of bridge-to-surgery (BTS) self-expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long-term BTS outcomes is unknown. We investigated the long-term outcomes of BTS colonic stenting using standardized SEMS placement. Methods This prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012-October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse-free survival (RFS), recurrence, and short-term outcomes of SEMS placement and surgery. Results The 1-, 3-, and 5-year OS rates were 94.1%, 77.4%, and 67.4%(Kaplan-Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1-, 3-, and 5-year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan-Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log-rank p = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio: 3.31; 95% confidence interval: 1.03-10.71, multivariate Cox regression). Conclusions This large, prospective, multicenter study revealed satisfactory long-term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to reduced perforation rate. (UMIN000007953).

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Transposon-encoded IscB family proteins are RNA-guided nucleases in the OMEGA (obligate mobile element-guided activity) system, and likely ancestors of the RNA-guided nuclease Cas9 in the type II CRISPR-Cas adaptive immune system. IscB associates with its cognate ωRNA to form a ribonucleoprotein complex that cleaves double-stranded DNA targets complementary to an ωRNA guide segment. Although IscB shares the RuvC and HNH endonuclease domains with Cas9, it is much smaller than Cas9, mainly due to the lack of the α-helical nucleic-acid recognition lobe. Here, we report the cryo-electron microscopy structure of an IscB protein from the human gut metagenome (OgeuIscB) in complex with its cognate ωRNA and a target DNA, at 2.6-Å resolution. This high-resolution structure reveals the detailed architecture of the IscB–ωRNA ribonucleoprotein complex, and shows how the small IscB protein assembles with the ωRNA and mediates RNA-guided DNA cleavage. The large ωRNA scaffold structurally and functionally compensates for the recognition lobe of Cas9, and participates in the recognition of the guide RNA–target DNA heteroduplex. These findings provide insights into the mechanism of the programmable DNA cleavage by the IscB–ωRNA complex and the evolution of the type II CRISPR-Cas9 effector complexes.

Background During endoscopic ultrasound-guided biliary drainage (EUS-BD), a combination of a 19-gauge needle and a 0.025-inch guidewire is generally used. However, a 19-gauge needle has poor maneuverability because of their stiffness and rigidity and might have poor penetrability in non-dilated bile ducts because of their large bore. In contrast, the application of a 22-gauge needle is expected to have improved maneuverability. However, only a 0.018-inch guidewire, which has less supportability, is applicable in the subsequent guidewire selection. This study aimed to evaluate the feasibility and safety of a dedicated bougie dilator for a 0.018-inch guidewire. Methods From September 2019 to May 2020, 26 patients underwent fistula dilation using the dilator after accessing the bile duct using a 22-gauge needle and a 0.018-inch guidewire during EUS-BD. The success and adverse event rates of EUS-BD were evaluated. Results Biliary access with a combination of a 22-gauge needle and a 0.018-inch guidewire was successful in all with a median bile duct diameter of 5 mm. Dilation of the fistula using the dedicated dilator was also successful in all cases. Subsequently, the dilator was successfully exchanged to an ERCP catheter that allowed for exchange to a 0.025-inch guidewire, except in one case where the catheter did not cross the fistula and a dilation balloon was inserted for an exchange to a 0.025-inch guidewire. The technical success rate of the EUS-BD was 100%. The adverse event rate was 19%. Conclusion The application of the dedicated dilator for a 0.018-inch guidewire was considered feasible and safe for EUS-BD.

Short-chain fatty acids (SCFAs), including propionate, are major metabolites of intestinal microorganisms and play an essential role in regulating intestinal epithelial integrity. Heat shock proteins (HSPs) promote cellular homeostasis under physiological and stressed conditions. This study aimed to investigate the regulation of intestinal HSP70 by propionate in human intestinal Caco-2 cells and the colon of fermentable dietary fiber (DF)-fed mice and germ-free mice. The results showed that propionate increased Hspa1a (HSP70 mRNA) level in Caco-2 cells, upregulated HSP70 protein, and phosphorylation of heat shock factor 1; however, the latter two were reduced by mitogen-activated protein kinases and the mechanistic target of rapamycin inhibitors. Feeding fermentable DFs, such as guar gum (GG) and partially hydrolyzed GG, increased both cecal SCFAs and colonic HSP70 expression, both of which were reduced in germ-free mice than in specific-pathogen-free mice. Collectively, the propionate-induced HSP70 expression was shown to be possibly involved in intestinal homeostasis.

Background: To investigate patient characteristics and the risk of post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in association with fluid volume and type during ERCP. Methods: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. Results: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). Conclusion: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.

Context: In adults, permissive hypercapnia reduces mortality and ventilation duration. However, in preterm infants, findings from past research regarding the efficacy and safety of permissive hypercapnia are controversial. Objective: To evaluate the efficacy and safety of permissive hypercapnia versus normocapnia in preterm infants on mechanical ventilation. Data Sources: MEDLINE, EMBASE, CENTRAL, and CINAHL Study Selection: Published randomized controlled trials (RCTs), non-RCTs, interrupted time series, cohort studies, case-control studies, and controlled before-and-after studies were included. Data Extraction: Two reviewers independently screened the title and abstract and full text, extracted data, assessed the risk of bias, and evaluated certainty of evidence (CoE) according to the Grading of Recommendations Assessment, Development and Evaluation approach. A meta-analysis of RCTs was performed using the random-effects model. Results: Four RCTs (693 infants) and one cohort study (371 infants) were included. No significant differences existed between the permissive hypercapnia and normocapnia groups for bronchopulmonary dysplasia (BPD) (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.74-1.18; very low CoE) and a composite outcome of death or BPD (RR 1.05; 95% CI 0.90-1.23; very low CoE). Permissive hypercapnia may increase necrotizing enterocolitis (RR 1.69; 95% CI 0.98-2.91; very low CoE), although the null or trivial effect cannot be excluded. No significant differences existed between the two groups for any other outcome assessed (very low-to-low CoE). Limitations: The sample sizes were less than the optimal sizes for all outcomes assessed, indicating the need for further trials. Conclusions: Permissive hypercapnia did not have any significant benefit or harm in preterm infants.

Background Liver failure and biliary tract cancer (BTC) are major life-threatening events in the clinical course of primary sclerosing cholangitis (PSC). Although these are competing events, they are typically evaluated as a composite prognostic endpoint. In Japan, the clinical characteristics and prognosis of PSC reportedly differ according to age of onset. We compared the prognosis of younger- versus older-onset PSC by competing risk analysis. Methods This was a retrospective analysis of 144 patients with PSC who were followed up for a median of 6.7 years. The patients were divided into two groups according to a cutoff age of onset of 44 years. We compared the prognosis of younger-onset PSC (n = 91) and older-onset PSC (n = 53) by competing risk analysis, incorporating mortality related and that unrelated to BTC as competing events. Results There was no difference in BTC-related mortality between patients with younger-onset and those with older-onset PSC (subdistribution hazard ratio [SHR], 0.89; 95% confidence interval [CI], 0.17-4.56, P = 0.888). The cumulative incidence of mortality due to other causes, including liver transplantation and liver failure, was non-significantly higher in patients with older-onset PSC (SHR, 1.58; 95% CI, 0.88-2.84; P = 0.129). Conclusions Although we did not find a significant difference in prognosis by onset age, patients with older-onset PSC had worse liver-transplantation-free survival than those with younger-onset PSC. A large cohort study is needed to evaluate the clinical outcomes of older- and younger-onset PSC.

Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an effective biliary drainage procedure in adult cases with difficult biliary access. However, there have been no reports on this procedure being used in pediatric cases. We successfully performed EUS-HGS in a pediatric case with a surgically altered anatomy. A standard convex-type echoendoscope and standard devices were used, and there were no device-related complications. The benefit of EUS-HGS for pediatric patients was avoidance of a percutaneous tube, which is difficult to maintain in active children. The accumulation of further cases and performance of a prospective study are warranted to standardize and expand the experience with this procedure.

A prospective single-center study was conducted to characterize the pharmacokinetics (PK) of fluconazole (FLCZ) in extremely low-birth-weight infants (ELBWIs) who received fosfluconazole (F-FLCZ). Intravenous F-FLCZ was administered at a dose of 3 mg/kg of body weight every 72 h during the first 2 weeks of life, every 48 h during the third and fourth weeks of life, and every 24 h after 5 weeks of life. Blood samples from ELBWIs treated with F-FLCZ were collected using scavenged samples. The concentration of FLCZ was determined using liquid chromatography-tandem mass spectrometry. The population pharmacokinetic model was established using Phenix NLME 8.2 software. In total, 18 ELBWIs were included in this analysis. Individual PK parameters were determined by a one-compartment analysis with first-order conversion. Postmenstrual age (PMA), serum creatinine (SCr), and alkaline phosphatase were considered covariates for clearance (CL). The mean population CL and the volume of distribution were 0.011 L/h/kg

Vancomycin (VCM) is useful for treating methicillin-resistant Staphylococcus aureus. In infants, calibrating the initial VCM dose is difficult, and many regimens have been proposed. For instance, our center uses the VCM regimen recommended for infants in the 2012-13 Nelson's Pediatric Antimicrobial Therapy. Nonetheless, our experience has shown that the initial VCM trough concentrations were frequently off target. We therefore analyzed the data on the initial VCM trough concentration in infant patients at our center.The study subjects were inborn infants born between July 2014 and June 2019 who were given VCM at earlier than day 60 in the neonatal intensive care unit. The primary outcome was the initial VCM trough concentration. The patients were divided into three groups by VCM trough concentration:10, 10-15, and15 mg/L. We also estimated VCM trough concentration by one method using Monte Carlo simulation, based on Nelson regimen dosage.Thirty-three patients were analyzed. The number of patients with10, 10-15, and15 mg/L was 24, 4, and 5, respectively. There was no significant difference in clinical characteristics between10 versus 10-15 and 10-15 versus15 mg/L. The numbers of patients with10, 10-15, and15 mg/L in the simulation were 26, 6, and 1, respectively.Most initial VCM trough concentrations were below the target. We could not find any significant clinical characteristics, which affected VCM trough concentration. Increasing the VCM dosage of the Nelson regimen with simulation should therefore be considered.

Background and study aim Management of bile duct stones (BDSs) in patients with surgically altered anatomies (SAAs) remains challenging. An endoscopic ultrasound-guided antegrade (EUS-AG) procedure and double-balloon enteroscopy-assisted endoscopic retrograde cholangiography (DB-ERC) have been used to remove BDSs from patients with SAAs. However, few comparative data have been reported. Therefore, we compared the efficacy and safety of the techniques. Methods This was a single-center retrospective study. Patients with SAA who underwent the EUS-AG procedure or DB-ERC to remove intra- or extra-BDSs between November 2010 and March 2020 were included. The primary outcome was the technical success rate, defined as stent insertion or stone removal during the initial session. The secondary outcomes were the procedure time, incidence of adverse events (AEs), and complete stone removal rate. Results Of the 54 patients enrolled, 23 underwent the EUS-AG procedure and 31 DB-ERC. The technical success rates of EUS-AG and DB-ERC were 87.0% and 64.5%, respectively (P = 0.11). The procedure time was significantly shorter in the EUS-AG group than in the DB-ERC group (51.9 ± 15.4 vs 72.6 ± 32.2 min; P = 0.01), and the early AE rates were 26.1% and 12.9%, respectively (P = 0.71). The complete stone removal rates in patients who underwent previous stone removal were 94.1% in the EUS-AG group and 85.7% in the DB-ERC group (P = 0.61). Conclusion The EUS-AG afforded technical success and complete stone removal rates comparable with those of DB-ERC, but the former procedure was shorter. The AE rate was acceptable.

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.

Background and aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. Methods A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. Results Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. Conclusions This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014.In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Background/Aims Recently, a three-plane symmetric needle with Franseen geometry was developed for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). In this retrospective study, tissue acquisition per pass was compared between 22-gauge Franseen FNB and standard fine needle aspiration (FNA) needles in patients with solid pancreatic lesions. Methods Consecutive patients who underwent EUS-FNA or EUS-FNB for solid pancreatic lesions between October 2014 and March 2018 were retrospectively studied. The tissue acquisition rate and the diagnostic performance per session, per pass, and at first pass were compared. Results A total of 663 passes (300 by the FNB needle and 363 by the standard FNA needle) were performed in 154 patients (71 FNB and 83 FNA). The tissue acquisition rate per session and at first pass in the FNB and FNA groups was 100% and 95% (p=0.13) and 87% and 69% (p=0.007), respectively. The multivariate analysis revealed that among the patients, EUS-FNB (odds ratio, 3.07; p=0.01) was associated with a higher first-pass tissue acquisition rate. While the tissue acquisition rate reached a plateau after the 4th pass with FNA, it reached a plateau after the 2nd pass with FNB. Among the 129 malignant cases, the histological tissue acquisition rate per session was similar (100% and 94%), but the sensitivity by histology alone per session was higher for FNB than for FNA (93% and 73%, p

Follow-up computed tomography revealed a 40-mm pancreatic tail cyst in a 59-year-old man with type 1 diabetes mellitus. An intraductal papillary mucinous neoplasm was suspected; mucinous cystic neoplasm (MCN) was not considered because the patient was a man. During follow-up, cyst infection occurred but was improved by conservative treatment. At the 24-month follow up examination, cyst nodules had developed, corresponding to an increase in the carbohydrate antigen 19-9 level. Mucinous cystadenocarcinoma (MCC) was diagnosed pathologically based on distal pancreatectomy. A diagnosis of male MCN/MCC is often delayed, which may lead to a poor prognosis. MCN infection is also rare and poorly recognized. We observed an atypical male case of MCN/MCC.

It remains unclear whether ursodeoxycholic acid (UDCA) treatment improves long-term outcomes in patients with primary sclerosing cholangitis (PSC). In this study, we investigated whether UDCA treatment is associated with improved liver transplantation (LT)-free survival in a cohort of Japanese patients with PSC.Journal instruction requires a city and country for affiliations; however, these are missing in affiliation [6]. Please verify if the provided city and country are correct and amend if necessary.'Tokyo, Japan' is correct.We used retrospective data from the Japanese PSC registry that included 435 patients with PSC. In this study, we enrolled patients with a complete dataset at diagnosis, along with the diagnosis year, treatment protocol, follow-up period, and outcome data. The association between UDCA treatment and all-cause death or LT was analyzed using Cox regression and inverse probability of UDCA treatment weighting (IPTW)-adjusted Cox regression models adjusted for covariates.Among 435 patients with PSC, 110 were excluded due to insufficient or missing data, and the remaining 325 patients (male, 187 (58%); mean age at diagnosis, 45.8 years) were enrolled. The mean follow-up period was 5.1 years, and 57 deaths and 24 LTs occurred during observation. UDCA was administered to 278 patients (86%). The Cox regression model demonstrated that UDCA treatment was associated with an improvement in LT-free survival [adjusted hazard ratio (aHR) 0.47, 95% confidence interval (CI) 0.28-0.78, p = 0.003]. In addition, the IPTW-adjusted model indicated a significant association between UDCA and LT-free survival (aHR 0.43, 95% CI 0.25-0.75, p = 0.020). Sensitivity analysis excluding patients treated with bezafibrate indicated a similarly significant association between UDCA treatment and LT-free survival.In this Japanese PSC cohort, UDCA treatment was significantly associated with improved LT-free survival.

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan.One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively.There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan.Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

Purpose. A phase I study of intraperitoneal paclitaxel (ip PTX) combined with gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) (GnP) was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in pancreatic cancer patients with peritoneal metastasis in first-line setting. Methods. Based on the 3 + 3 dose-escalation model, ip PTX, GEM and nab-PTX were administered at doses of 20 or 30 mg/m2, 800 or 1000 mg/m2 and 100 or 125 mg/m2 (level 1, 2 and 3, respectively) on days 1, 8 and 15 in 4-week cycles. Dose-limiting toxicity (DLT) defined as severe adverse events was evaluated during the first cycle of the treatment. Safety and preliminary efficacy were also investigated. Results. In total, 12 patients were enrolled. While 2 of the first 6 patients enrolled at level 1 experienced DLTs (grade 3 ip port dysfunction and grade 3 pneumonia), no DLT was observed in the next 6 patients enrolled at level 2 and 3. Therefore, we did not reach the MTD and the RD was determined to be level 3 (ip PTX of 30 mg/m2, GEM of 1000 mg/m2, and nab-PTX of 125 mg/m2). The major grade 3/4 adverse events included neutropenia (58%), anemia (33%), and ip port dysfunction (25%). The response rate was 25% and the median PFS was 5.4 (95% confidence interval; 2.4–16.0). The cytological status in peritoneal lavage turned negative in 8 patients (67%). Conclusions. Ip PTX combined with GnP was feasible and potentially effective in pancreatic cancer with peritoneal metastasis as a first-line treatment deserved further evaluations.

Endoscopic ultrasonography (EUS)-guided interventions are often performed using a single guidewire (SGW), but there are a few reports on the use of double guidewire (DGW) technique to facilitate multiple drainage placement during EUS-guided drainage of pancreatic fluid collections. This DGW technique may have advantages other than multiple drainage placement during EUS-guided interventions such as scope stabilization, support for stone extraction and device insertion. Consecutive patients who underwent EUS-guided interventions between Feb 2012 and Apr 2019 were retrospectively reviewed. The rate and reasons of DGW technique, and clinical outcomes were evaluated. DGW technique was performed, using an uneven double lumen cannula (UDLC), which facilitates insertion of 0.025-in. and 0.035-in. guidewires. A total of 249 EUS-guided interventions were analyzed, and DGW technique was utilized primarily in 65 cases (25.7%) and as a salvage after failed SGW technique in 18 cases (7.1%). The reasons for DGW technique were 60 multiple drainage placement, 10 scope stabilization, 7 device insertion, 5 safety guidewire, and 4 antegrade stone removal. Insertion of UDLC and DGW was successful in 100%. Technical success rate of preplanned interventions was 92.7% (96.9% in primary DGW and 77.8% in salvage DGW technique). Adverse events were observed in 19.5% after DGW but were not related to DGW technique. DGW technique using UDLC during EUS-guided interventions was technically feasible and safe. In addition to multiple drainage insertion, it can potentially support complex EUS-guided interventions.

OBJECTIVES Colorectal stenting is widely performed using self-expandable metallic stents (SEMSs), but the mechanical properties have not been evaluated. Therefore, we conducted an in vitro study to evaluate the mechanical properties of colorectal SEMSs. METHODS Eighteen individual types and sizes of uncovered SEMSs were evaluated for their mechanical properties. Radial force was measured using a measurement machine. Axial force (AF) was measured by two methods: a conventional manual method and a new method using a measurement machine. The correlation of these two methods was evaluated. We also proposed an "AF zero border" that was defined as the angle at which the torque force disappeared. RESULTS Radial force versus diameter curves and AF versus angle curves were influenced by the structure and the size of each stent. There was excellent correlation of AFs measured by the new and conventional manual method (y = 21.434x, R = 0.881, P

BACKGROUND AND AIM Limited data are available on age and comorbidity assessment in patients with biliary tract cancer (BTC). This study aimed to evaluate the association of age and comorbidity burden with clinical outcomes of chemotherapy for BTC. METHODS Consecutive 197 BTC patients undergoing first-line chemotherapy between 2007 and 2017 were retrospectively studied. Patients were classified to three groups according to the age-adjusted Charlson comorbidity index (ACCI) excluding the score about BTC and progression-free survival, overall survival (OS), and safety were compared. RESULTS Fifty-one patients (26%) were elderly (≥ 75 years), and ACCI was 0-2 in 73 patients (37%), 3-4 in 98 (50%), and ≥ 5 in 26 (13%). ACCI was associated with the administration of first-line combination chemotherapy (89% in 0-2, 80% in 3-4, and 64% in ≥ 5, P

Background/Aims: The aim of this study was to evaluate the safety and efficacy of partially covered self-expandable metallic stents (PCSEMS) in patients undergoing neoadjuvant chemo (radio) therapy (NAC) for pancreatic cancer (PC). Methods: This was a prospective multicenter study to evaluate the safety and efficacy of PC-SEMS in patients receiving NAC for resectable and borderline resectable PC. The primary endpoint was the rate of recurrent biliary obstruction (RBO). Results: Twenty-six patients with PC (three with resectable PC and 23 with borderline resectable PC) who underwent NAC at seven Japanese centers were included in the analysis. Both the technical and functional success rates of PCSEMS placement were 100%. Early stent-related complications were observed in three patients (11.5%): mild pancreatitis (n=2) and mild liver abscess (n=1). The median time to surgery or palliation was 4.0 months. Surgical resection was eventually performed in 73.1% of patients, and stent removal during surgery was successful in all patients. RBO was observed in nine patients (34.6%): seven with stent occlusion, one with kinking and one with migration. The RBO rates in resected cases and nonresected cases were 36.8% and 28.6%, respectively. Conclusions: Biliary drainage by PCSEMS was safe and feasible in patients undergoing NAC for resectable and borderline resectable PC. (Gut Liver 2021;15:135-141)

Objectives To clarify the significance of ultrasonographically recorded pancreatic duct dilatation. Methods Various parameters predicting pancreatic disease were evaluated in relation to pancreatic duct dilatation using data from medical checkups of healthy examinees. Results Records of 281,384 subjects were analyzed. Pancreatic duct dilatation (≥3 mm) was determined ultrasonographically in 524 patients (0.19%). Subsequent detailed examinations revealed the presence of pancreatic disease in 24.8% of these patients, including pancreatic cysts (15.6%) and chronic pancreatitis (4.9%). Pancreatic cancer was found in 6 cases (1.3%). Predictive factors of pancreatic diseases in examinees with pancreatic duct dilatation were investigated, and the diameter of the pancreatic duct (p

Background While endoscopic management of benign biliary strictures (BBSs) is the standard of care, long-term treatment remains the issue in refractory cases, especially for anastomotic strictures after living-donor liver transplantation (LDLT) and hepaticojejunostomy anastomotic strictures (HJAS). The aim of this prospective study was to evaluate the safety and effectiveness of a fully covered self-expandable metal stent (FCSEMS) for patients with refractory BBSs. Methods Patients with BBSs that were unamenable to endoscopic plastic stent placement with a treatment period of more than 6 months were eligible. An FCSEMS was placed endoscopically and removed after 90 days. In patients with surgically altered anatomy, an FCSEMS was placed using a double-balloon endoscope. The primary outcome was stricture resolution at FCSEMS removal. The secondary outcomes included stricture recurrence and adverse events. Results A total of 30 patients were enrolled: the causes of their BBSs were anastomotic stricture after LDLT in 13, HJAS in 12, post-cholecystectomy in two, chronic pancreatitis in two, and post-hepatectomy in one. The technical success rate of FCSEMS placement was 100 % and all FCSEMSs were successfully removed. The rate of stricture resolution at FCSEMS removal was 96.6 % (91.7 % in the post-LDLT group and 100 % in the HJAS group). Stricture recurrence occurred in three HJAS patients (10.7 %) during a median follow-up period of 15.6 months. Adverse events were observed in 12.1 %: five cholangitis, one pancreatitis, and one perforation. Conclusion Temporary placement of an FCSEMS was a feasible and effective treatment option for refractory BBSs, especially for post-LDLT strictures and HJAS.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Objective To compare admission and emergency visits of late preterm (340/7–366/7 weeks) versus term infants (370/7–416/7 weeks) in the first 5 years. Study Design This population-based cohort study included all singletons and twins born alive at 340/7 to 416/7 weeks' gestation registered in a health administrative database in Ontario, Canada, between April 1, 2002 and December 31, 2012. Admissions and emergency visits from initial postnatal discharge to 5 years were compared between late preterm and term infants adjusting for maternal and infant characteristics. Results A total of 1,316,931 infants (75,364 late preterm infants) were included. Late preterm infants had more frequent admissions than term infants in the first 5 years in both singletons (adjusted incidence rate ratio [95% confidence interval] = 1.46 [1.42–1.49]) and twins (1.21 [1.11–1.31]). The difference in admissions between late preterm and term infants were smaller in twins than singletons and decreased with children's ages. Twins had less frequent admissions than singletons for late preterm infants, but not for term infants. The emergency visits were more frequent in late preterm than term infants in all the periods. Conclusion Admissions and emergency visits were more frequent in late preterm than term infants through the first 5 years. Admissions were less frequent in late preterm twins than singletons.

Metabolism is a critical regulator of cell fate determination. Recently, the significance of metabolic reprogramming in environmental adaptation during tumorigenesis has attracted much attention in cancer research. Recurrent mutations in the isocitrate dehydrogenase (IDH) 1 or 2 genes have been identified in several cancers, including intrahepatic cholangiocarcinoma (ICC). Mutant IDHs convert α-ketoglutarate (α-KG) to 2-hydroxyglutarate (2-HG), which affects the activity of multiple α-KG-dependent dioxygenases including histone lysine demethylases. Although mutant IDH can be detected even in the early stages of neoplasia, how IDH mutations function as oncogenic drivers remains unclear. In this study, we aimed to address the biological effects of IDH1 mutation using intrahepatic biliary organoids (IBOs). We demonstrated that mutant IDH1 increased the formation of IBOs as well as accelerated glucose metabolism. Gene expression analysis and ChIP results revealed the upregulation of platelet isoform of phosphofructokinase-1 (PFKP), which is a rate-limiting glycolytic enzyme, through the alteration of histone modification. Knockdown of the Pfkp gene alleviated the mutant IDH1-induced increase in IBO formation. Notably, the high expression of PFKP was observed more frequently in patients with IDH-mutant ICC compared to in those with wild-type IDH (p

Background/Aims: We aimed to investigate incidence, characteristics, and possible risk factors of pancreatic cancer in patients under observation for hepatocellular carcinoma (HCC) because the association of hepatitis virus B infection and pancreatic cancer has been reported. Patients and Methods: We performed a retrospective cohort study in the Gastroenterology Department of a University Hospital in Japan between 2004 and 2012. A total of 1848 patients who underwent treatment for HCC were included at the initiation of treatment for HCC (mean follow-up period, 33.6 months). The patients received trimonthly radiological follow-ups. Newly developed cases of pancreatic cancer during follow-up for HCC were compared with that of an age- and sex-matched theoretical cohort from national statistics. Possible predisposing factors for pancreatic cancer related to HCC were assessed. Cumulative probabilities of developing a pancreatic cancer were compared using log-rank test. Results: About 13 of 1848 patients developed pancreatic cancer (mean follow-up period, 45.2 months). The risk ratio for all patients was 3.02 (log-rank test: P =0.01). Statistical analyses showed no effects of the following factors on the development of pancreatic cancer: age, sex, follow-up period, alcohol intake, laboratory data, presence of hepatitis virus, characteristics of HCC, type of treatment, number of radiological examinations, and cumulative effective dose. Conclusions: Increased incidence of pancreatic cancer was found in patients under observation for HCC in a relatively small cohort. HCC or other common underlying conditions might be a risk factor for development of pancreatic cancer.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. There are no established serum biomarkers for predicting the outcomes of IPF. S100 calcium-binding protein A4 (S100A4) is considered as a marker of fibroblasts; however, its clinical application remains to be investigated. We evaluated the clinical relevance of S100A4 in IPF patients.Serum S100A4 levels in 95 consecutive IPF patients and 50 healthy controls (HC) were measured using enzyme-linked immunosorbent assay. S100A4 expression in lung tissues was determined using immunohistochemistry/immunofluorescence and its association with disease progression (defined as deterioration in lung function or death) and mortality was assessed using Kaplan-Meier method and Cox hazards analysis.Serum S100A4 levels were undetectable in all HC but were detectable in 26 (27.3%) of the 95 IPF patients (P 0.01). Immunostaining of lung tissues from IPF patients showed aggregation of numerous S100A4-expressing cells around the fibroblastic foci and mature fibrotic regions. IPF patients with higher serum S100A4 levels had a significantly worse prognosis than those with low serum levels (2-year cumulative survival rate: 41.7% vs 77.0%, respectively, P 0.01). On multivariate analyses, baseline serum S100A4 levels (per 10 ng/mL increase) were independently associated with higher disease progression rate (odds ratio: 1.06, P = 0.01) and higher mortality (hazard ratio: 1.18, P = 0.03).S100A4 is a promising serum biomarker that may help predict disease progression/mortality. Our findings may help establish treatment strategies for IPF.

The type III-E CRISPR-Cas effector Cas7-11, with dual RNase activities for precursor CRISPR RNA (pre-crRNA) processing and crRNA-guided target RNA cleavage, is a new platform for bacterial and mammalian RNA targeting. We report the 2.5-Å resolution cryoelectron microscopy structure of Cas7-11 in complex with a crRNA and its target RNA. Cas7-11 adopts a modular architecture comprising seven domains (Cas7.1-Cas7.4, Cas11, INS, and CTE) and four interdomain linkers. The crRNA 5' tag is recognized and processed by Cas7.1, whereas the crRNA spacer hybridizes with the target RNA. Consistent with our biochemical data, the catalytic residues for programmable cleavage in Cas7.2 and Cas7.3 neighbor the scissile phosphates before the flipped-out fourth and tenth nucleotides in the target RNA, respectively. Using structural insights, we rationally engineered a compact Cas7-11 variant (Cas7-11S) for single-vector AAV packaging for transcript knockdown in human cells, enabling in vivo Cas7-11 applications.

In Japan, the definition and classification of neonatal chronic lung disease (CLD) used for its diagnosis are a combination of those used in Japan and abroad.To clarify the current state of CLD diagnosis, a questionnaire survey was conducted.Half of the patients of the medical centers included in the study were diagnosed with CLD in real time, while the other half were diagnosed after discharge. In addition, in approximately 70% of the facilities, diagnosis was made after discussions various among medical teams. In approximately 80% of the centers, the chest radiography used for CLD diagnosis were evaluated by multiple doctors. Furthermore, some centers used chest X-rays that were taken at approximately 28 days of age for CLD diagnosis, whereas at other facilities, diagnosis was made regardless of time at which the chest radiography were obtained. Only a small number of centers have established criteria for determining the necessity of oxygen at the corrected age of 36 weeks, and the target saturation of peripheral oxygen levels also tend to vary for each facility. Whether the conditions wherein the patient receives respiratory support for apnea or respiratory tract diseases should be considered as CLD also differed among the facilities.It is necessary to reassess the definition and classification of CLD in Japan to accurately evaluate and improve the quality of respiratory management based on the long-term prognosis.

CONTEXT For many years the International Liaison Committee on Resuscitation has recommended the use of tactile stimulation for initial management of infants born with inadequate respiratory effort at birth without systematically examining its effectiveness. OBJECTIVE Systematic review to compare the effectiveness of tactile stimulation with routine handling in newly born term and preterm infants. DATA SOURCES Medline, Embase, Cochrane CENTRAL, along with clinical trial registries. STUDY SELECTION Randomized and non-randomized studies were included based on predetermined criteria. DATA EXTRACTION Data were extracted independently by authors. Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) was used to assess risk of bias in non-randomized studies. Grading of Recommendations, Assessment, Development and Evaluations (GRADE) was used to assess the certainty of evidence. RESULTS Among 2455 unique articles identified, 2 observational studies were eligible and qualitatively summarized. Because one of the studies was at critical risk of bias, only the other study including 243 preterm infants on continuous positive airway pressure with clinical indications for tactile stimulation was analyzed. It showed a reduction in tracheal intubation in infants receiving tactile stimulation compared with no tactile stimulation (12 of 164 vs 14 of 79, risk ratio of 0.41 [95% confidence interval 0.20 to 0.85]); however, the certainty of evidence was very low. LIMITATIONS The available data were limited and only from observational studies. CONCLUSIONS A potential benefit of tactile stimulation was identified but was limited by the very low certainty of evidence. More research is suggested to evaluate the effectiveness as well as the optimal type and duration of tactile stimulation.

Objective: This study was carried out to understand the disparities in mortality and survival without major morbidities among very premature and very low birth weight infants between participating Neonatal Intensive Care Units (NICUs) from the Brazilian Network on Neonatal Research (RBPN) and the Neonatal Research Network of Japan (NRNJ). Methods: Secondary data analysis of surveys by the RBPN and NRNJ was performed. The surveys were conducted in 2014 and 2015 and included 187 NICUs. Primary outcome was mortality or survival without any major morbidity. Logistic regression analysis adjustment for confounding factors was used. Results: The study population consisted of 6,406 infants from the NRNJ and 2,319 from the RBPN. Controlling for various confounders, infants from RBPN had 9.06 times higher adjusted odds of mortality (95%CI 7.30–11.29), and lower odds of survival without major morbidities (AOR 0.36; 95%CI 0.32–0.41) compared with those from the NRNJ. Factors associated with higher odds of mortality among Brazilian NICUs included: Air Leak Syndrome (AOR 4.73; 95%CI 1.26–15.27), Necrotizing Enterocolitis (AOR 3.25; 95%CI 1.38–7.26), and Late Onset Sepsis (LOS) (AOR 4.86; 95%CI 2.25–10.97). Conclusions: Very premature and very low birth weight infants from Brazil had significantly higher odds for mortality and lower odds for survival without major morbidities in comparison to those from Japan. Additionally, we identified the factors that increased the odds of in-hospital neonatal death in Brazil, most of which was related to LOS. RESUMO Objetivo: Este estudo foi realizado para compreender as disparidades na mortalidade e sobrevivência sem as principais morbidades entre recém-nascidos muito prematuros e de muito baixo peso entre Unidades de Terapia Intensiva Neonatal (UTINs) participantes da Rede Brasileira de Pesquisas Neonatais (RBPN) e Rede de Pesquisa Neonatal do Japão (NRNJ). Métodos: Foi realizada uma análise dos dados secundários dos bancos de dados da RBPN e da NRNJ. As pesquisas foram realizadas em 2014 e 2015 e incluíram 187 UTINs. O desfecho primário foi mortalidade ou sobrevida sem qualquer morbidade importante. Utilizou-se a análise de regressão logística com ajuste para os fatores de confusão. Resultados: A população do estudo foi composta por 6.406 recém-nascidos do NRNJ e 2.319 do RBPN. Ajustando para diversos fatores de confusão, os prematuros da RBPN tiveram 9,06 vezes maiores chances de mortalidade (IC95% 7,30–11,29) e menores chances de sobrevivência sem morbidades importantes (AOR 0,36; IC95% 0,32–0,41) em comparação com os da NRNJ. Fatores associados a maiores chances de mortalidade entre as UTINs brasileiras incluíram: síndrome de escape de ar (AOR 4,73; IC95% 1,26–15,27), enterocolite necrosante (AOR 3,25; IC95% 1,38–7,26) e sepse de início tardio (AOR 4,86; IC95% 2,25–10,97). Conclusões: Os recém-nascidos muito prematuros e de muito baixo peso do Brasil apresentaram chances significativamente maiores de mortalidade e menores chances de sobrevivência sem as principais morbidades em comparação aos do Japão. Além disso, identificamos os fatores que aumentam as chances da morte neonatal no Brasil, sendo a maioria relacionada à sepse tardia.