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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).

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.

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.

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.

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.

Introduction: Despite changes in prenatal diagnostic methods and perceptions regarding the prognosis of and treatment options for patients with trisomy 18 syndrome, data on the secular changes in patient survival are limited. This study aimed to investigate the survival pattern for such patients. Methods: To investigate the general patient survival patterns, we used data from the vital statistics database of deaths in Japan from 1975 to 2016. We described demographic factors, such as sex, gestational age at delivery, and surgical history, for patients whose primary cause of death was trisomy 18 syndrome. Results: The proportions of deaths within 24 h of birth (4.0% in 1975–1980 to 21.9% in 2011–2016) and at age ≥1 year (8.9% in 1975–1980 to 17.7% in 2011–2016) increased. The median survival time was higher for females, infants born after 37 weeks of gestation, and those who received surgical intervention. The median survival time tripled among patients who received surgical intervention (61.5 days in 1995–2005 to 182.5 days in 2006–2016), and the proportion of such patients increased (from 3.8% in 1995 to 24.1% of the entire affected population in 2016). Discussion/Conclusion: In Japan, the median survival time of infants with trisomy 18 increased over time, and the proportion of death within 24 h and at ≥1 year increased. Greater acknowledgement of the possible benefits of surgical intervention likely led to the increased provision of interventions and contributed to the increased survival time.

Background Interventional endoscopic ultrasound-guided procedures (I-EUS) are widely accepted as salvage procedures in ERCP-failed cases, and to drain fluid collected in the abdominal cavity. Although I-EUS has a relatively high incidence of complications and is severe/fatal in some cases, no follow-up strategy has been established. In our institution, plain computed tomography (P-CT) is performed routinely the day after I-EUS. In this study, we evaluated the usefulness of routine P-CT the day after I-EUS, as a follow-up method, and propose an algorithm. Methods We retrospectively reviewed 81 patients who underwent I-EUS and evaluated the usefulness of P-CT, abdominal X-ray, laboratory data, and symptoms as a follow-up method. An adverse event (AE) was defined as an event requiring any treatment. Results Technical success, clinical success, and AE rates were 96.3%, 90.1%, and 18.9%, respectively. In total, 30 patients had abnormal findings among the follow-up methods: 6 cases underwent additional procedures, 8 underwent medical treatments, and 16 were observed. The sensitivity, specificity, and accuracy for detecting AEs were assessed based on P-CT (85.7%, 100%, and 97.5%), X-ray (7.1%, 100%, and 83.5%), laboratory data (71.4%, 83.0%, and 81.0%), and symptoms (92.9%, 86.2%, and 87.3%). The sensitivity and accuracy of the latter two items were as high as those for X-ray, but specificity was lower than those for X-ray and P-CT. Conclusions Routine P-CT the day after I-EUS was useful for detecting complications and deciding to perform an invasive salvage procedure. Symptoms and laboratory data were useful to supplement routine P-CT.

Introduction Congenital complete atrioventricular block (CCAVB) associated with congenital chylothorax is a rare finding that has been reported in only one case in the literature. We report here the case of an infant with CCAVB complicated by congenital chylothorax. Patient Report We present the case of a male neonate with a birth weight of 2114 g. Fetal bradycardia and right pleural effusion were detected at gestational age of 22 weeks. Maternal serum levels of anti-Sjögren's-syndrome-related antigen A autoantibody were high (4840 U/mL). The neonate was delivered at gestational age of 33 weeks; a temporary external pacemaker was placed immediately after birth that resulted in an improved cardiac output. Milk-colored pleural effusion increased in volume together with the initiation of breast milk feeding. Lymphocytosis and high triglyceride levels in the pleural fluid led to the diagnosis of chylothorax. The pleural effusion resolved in response to prednisolone, octreotide, and total parenteral nutrition. Discussion The causal relationship between CCAVB and congenital chylothorax can be explained by considering the damage to the lymphatic vessels secondary to inflammation due to maternal autoantibodies and venous congestion due to bradycardia. Conclusion In any case of CCAVB associated with atypical pleural effusion, one must consider the possibility of congenital chylothorax.

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.

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.

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

In patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial. Clinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS. A total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively. Other than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.

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.

Background/Aim: A sufficiently open papilla is needed to remove common bile duct stones (CBDS) but endoscopic sphincterotomy (EST) requires a high level of skill and is difficult with endoscopic papillary balloon dilation (EPBD). The main adverse event of EST is bleeding and perforation and that of EPBD is post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. To reduce these adverse events we employed minimal EST followed by papillary dilation (ESBD), and retrospectively evaluated its efficacy and safety compared with EST. Patients and Methods: CBDS patients who underwent EST (n = 114) or ESBD (n = 321) at Juntendo University Hospital from January 2009 to December 2018 were consecutively enrolled, retrospectively. The exclusion criteria were large-balloon dilation (≥ 12 mm), large CBDS (>12 mm), and previous EST/EPBD. We compared the overall stone removal rate, incidence of adverse event, procedure time, number of ERCP procedures, and rate of mechanical lithotripsy (ML) between the two groups. Results: Complete stone removal was successful in both ESBD and EST group. However, the rate of multiple ERCP sessions was significantly lower (35.1% vs. 12.8%, P < 0.001), procedure time was shorter (31.6 vs. 25.8 min, P = 0.01), and rate of ML was lower (16.7% vs. 7.8%, P = 0.01) in ESBD group. Bleeding was significantly more frequent in the EST group (9.6% vs. 1.2%, P < 0.001), particularly acute bleeding (7.9% vs. 0.9%, P < 0.001). Conclusions: ESBD is more efficient and safer in the management of CBD stones than EST. A prospective randomized study comparing ESBD with EST is needed to establish this combination technique.

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.

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.

(1) Background: Endoscopic colorectal stenting with high technical success and safety is essential in discussing the oncological outcomes for the management of malignant colorectal obstruction. Mechanical properties of self-expandable metal stents are usually considered to affect clinical outcomes. (2) Methods: A multicenter, prospective study was conducted in Japan. A self-expandable metal stent with low axial force was inserted endoscopically. The primary endpoint was clinical success, defined as the resolution of symptoms and radiological findings within 24 h. Secondary endpoints were technical success and adverse events. Short-term outcomes of 7 days were evaluated in this study. (3) Results: Two hundred and five consecutive patients were enrolled. Three patients were excluded, and the remaining 202 patients were evaluated. The technical and clinical success rates were 97.5% and 96.0%, respectively. Major stent-related adverse events included stent migration (1.0%), insufficient stent expansion (0.5%), and stent occlusion (0.5%). No colonic perforation was observed. There were two fatal cases (1%) which were not related to stent placement. (4) Conclusions: The placement of self-expandable metal stents with low axial force is safe with no perforation and showed high technical and clinical success rates in short-term outcomes for the management of malignant colorectal obstruction.

A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (&gt, 2, &gt, 3, and &gt, 4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration &gt, 2 months was not associated with overall survival (p = 0.1), while &gt, 3 months was significantly associated with survival (p =.04). In multivariate analysis, a reduction duration &gt, 3 months predicted a good long-term prognosis (odds ratio = 5.75, 95% confidence interval = 1.47–22.36, p &lt, 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.

Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is becoming increasingly popular. However, the risk factors for stent migration into the abdominal cavity remain unknown. Methods: Forty-eight patients undergoing EUS-HGS with placement of a long, partially covered self-expandable metallic stent (LPC-SEMS) were studied retrospectively to identify risk factors of stent migration. We determined the technical and functional success rates, and recorded adverse events, including stent migration. Results: EUS-HGS was technically successful in all patients. However, stent migration was evident in five patients (one actual and four imminent, 10%). Stent migration into the abdominal cavity was observed in one patient (2%), and the other four cases required additional procedures to prevent migration (8%). Logistic regression analysis revealed that the risk of stent migration increased as the initial (pre-procedure) distance between the stomach and liver at the puncture site increased (p = 0.012). Conclusions: A longer distance between the stomach and liver at the puncture site increased the risk of stent migration. However, during EUS-HGS, it is difficult to adjust the puncture position. It is important to ensure that the proportion of the stent in the stomach is large, the use of a self-anchoring stent may be optimal.

Video Video 1 Percutaneous cholangioscopy was performed to confirm complete closure of the choledochojejunostomy. Percutaneous cholangioscopy revealed complete closure of the anastomosis. Our attempt to pass a guidewire through the anastomosis failed accordingly.

There is inconsistent evidence suggesting the clinical relevance of the early detection of future needs of preterm patent ductus arteriosus (PDA) surgery. We tested the hypothesis that echocardiographic indices at 3 days of age predict the future need for PDA surgery.We analyzed a database including the clinical and echocardiographic data of 710 preterm infants with gestational ages between 23 and 29 weeks in 34 Japanese neonatal intensive care units, and prospectively collected data over 14 months. The predictive or discriminative ability of each echocardiographic index at 3 days of age for future PDA surgical closure was evaluated using multivariable logistic regression analyses with adjustment for gestational age, sex, and small-for-gestational-age status, according to the areas under the receiver-operating characteristic curves (AUCs) of the models.A total of 688 eligible patients (median gestational age: 26 weeks, body weight at birth: 843 g) were analyzed, of whom 77 (11%) underwent PDA surgery (median age: 21 days) after full consideration of clinical conditions. The AUC of PDA diameter (PDAd) was the largest, followed by that of the left pulmonary artery end-diastolic velocity (LPAedv). Compared with the ratio of left atrial-to-aorta diameter (AUC 0.76), PDAd (AUC 0.84, p0.001) and LPAedv (AUC 0.82, p = 0.003) were significantly better predictors of future PDA surgery.Echocardiographic indices at 3 days of age, especially PDAd and LPAedv, may predict the future need for surgical closure of PDA in preterm infants.

Background and aims: The goals of the management of benign biliary stricture (BBS) are to relieve symptoms and resolve short-/long-term stricture. We performed fully covered self-expandable metallic stent (hereafter, FCSEMS) placement for BBS using various methods and investigated the treatment outcomes and adverse events (AEs). Methods: We retrospectively studied patients who underwent FCSEMS placement for refractory BBS through various approaches between January 2017 and February 2020. FCSEMS were placed for 6 months, and an additional FCSEMS was placed if the stricture had not improved. Technical success rate, stricture resolution rate, and AE were measured. Results: A total of 26 patients with BBSs that were difficult to manage with plastic stents were included. The mean overall follow-up period was 43.3 ± 30.7 months. The cause of stricture was postoperative (46%), inflammatory (31%), and chronic pancreatitis (23%). There were four insertion methods: endoscopic with duodenoscopy, with enteroscopy, EUS-guided transmural, and percutaneous transhepatic. The technical success rate was 100%, without any AE. Stricture resolution was obtained in 19 (83%) of 23 cases, except for three cases of death due to other causes. Stent migration and cholangitis occurred in 23% and 6.3%, respectively. Stent fracture occurred in two cases in which FCSEMSs were placed for more than 6 months (7.2 and 10.3 months). Conclusion: FCSEMS placement for refractory BBS via various insertion routes was feasible and effective. FCSEMSs should be exchanged every 6 months until stricture resolution because of stent durability. Further prospective study for confirmation is required, particularly regarding EUS-guided FCSEMS placement.

Context Parent/family presence at pediatric resuscitations has been slow to become consistent practice in hospital settings and has not been universally implemented. A systematic review of the literature on family presence during pediatric and neonatal resuscitation has not been previously conducted. Objective To conduct a systematic review of the published evidence related to family presence during pediatric and neonatal resuscitation. Data sources Six major bibliographic databases was undertaken with defined search terms and including literature up to June 14, 2020. Study selection 3200 titles were retrieved in the initial search; 36 ultimately included for review. Data extraction Data was double extracted independently by two reviewers and confirmed with the review team. All eligible studies were either survey or interview-based and as such we turned to narrative systematic review methodology. Results The authors identified two key sets of findings: first, parents/family members want to be offered the option to be present for their child’s resuscitation. Secondly, health care provider attitudes varied widely (ranging from 15% to >85%), however, support for family presence increased with previous experience and level of seniority. Limitations English language only; lack of randomized control trials; quality of the publications. Conclusions Parents wish to be offered the opportunity to be present but opinions and perspectives on the family presence vary greatly among health care providers. This topic urgently needs high quality, comparative research to measure the actual impact of family presence on patient, family and staff outcomes. PROSPERO registration number CRD42020140363.

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.

Background and aims The anastomotic biliary stricture is a clinically important complication after living donor liver transplantation (LDLT) with a duct-to-duct anastomosis. Although endoscopic management of post-LDLT biliary strictures using balloon dilation (BD) and plastic stents (PSs) has provided acceptable short-term outcomes, long-term outcomes and prognostic factors for treatment success remain unclear. Methods We included 96 patients with post-LDLT biliary strictures who were endoscopically managed between 2003 and 2016. BD was utilized as a first-line treatment strategy, and PS placement was carried out for refractory cases. Potential prognostic factors for biliary stricture resolution were analysed using logistic regression analyses. Results Endoscopic treatment was technically successful in 84 patients (87.5%). The overall rate of biliary stricture resolution was 44.8% (43 of 96 patients) with a median follow-up duration of 90.9 months (interquartile range, 30.9-122.3 months). Bile duct kinking was associated with a lower rate of biliary stricture resolution (odds ratio, 0.33; 95% confidence interval, 0.13-0.87). After successful endoscopic treatment, biliary strictures recurred in 22 patients (57.9%) after BD, and in one patient (4%) after PS treatment. Conclusions Despite a high technical success rate, endoscopic treatment only provided a low rate of resolution of anastomotic biliary strictures among LDLT patients and required prolonged treatment duration. Alternative strategies including the use of a covered metal stent should be evaluated to further improve the treatment outcomes of post-LDLT biliary strictures, particularly in those accompanied by the bile duct kinking.

Due to increasing opportunities for abdominal imaging studies, bile duct stones are occasionally diagnosed without any symptoms. However, there has been no consensus on the management of asymptomatic bile duct stones. We conducted a retrospective longitudinal cohort study to investigate the natural history of asymptomatic bile duct stones and clinical outcomes according to the timing of endoscopic removal. We identified consecutive patients who were diagnosed with asymptomatic common bile duct stones and categorized into those who were followed up with stones in situ (wait-and-see group) and those who received early endoscopic stone removal (intervention group). Cumulative incidence functions of biliary complications were estimated and compared between the groups. We included 191 patients (114 patients in the wait-and-see group and 77 patients in the intervention group). In the wait-and-see group, the cumulative incidence of biliary complications was 6.1% at 1 year, 11% at 3 years, and 17% at 5 years. Asymptomatic disappearance of stones was observed in 22 patients (19%). Procedure-related adverse events of early endoscopic stone removal of asymptomatic stones were observed in 25 (32%) patients including 4 (5.2%) with severe pancreatitis. The cumulative incidence function of biliary complications did not differ by treatment strategies (P = 0.55). Biliary complications occurred in a substantial proportion of patients with asymptomatic bile duct stones, but early endoscopic removal appeared to have little effect on the prevention of further biliary complications. Given the risk of procedure-related pancreatitis, the wait-and-see strategy may become a management option of asymptomatic stones.

Autoimmune pancreatitis (AIP) is frequently complicated by diabetes mellitus (DM), but DM associated with AIP is reported to improve after steroid therapy. The aim of this study is to investigate glucose intolerance during steroid therapy according to the onset of DM. Sixty-one patients who underwent steroid therapy for AIP were included into this study. We evaluated C peptide index (CPI), homeostasis model assessment for insulin resistance (HOMA-R), and the pancreatic diameter at AIP diagnosis and after 4 weeks, 1 year, and 2 years of steroid therapy. Patients were categorized into three groups according to DM onset: Pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). Forty-three patients (71%) had DM: 15 pDM and 28 cDM. At AIP diagnosis, CPI was lower in patients with pDM (0.7, P = 0.007) and cDM (0.9, P = 0.018) than nDM (1.3). After 4 weeks of steroid therapy, CPI improved in cDM (P < 0.001) and in nDM (P = 0.021). After 2 years of steroid therapy, HOMA-R increased (2.1–3.0, P = 0.007) but CPI gradually improved (1.0–2.1, P = 0.004). DM improved in 23% of cDM, and 55% of insulin users in cDM discontinued using insulin. Pancreatic atrophy was seen in 30%, and was associated with DM. DM in patients with AIP was associated with impaired insulin secretion rather than insulin resistance. Insulin secretion improved during steroid therapy for AIP in patients with concurrent DM. Thus, glucose intolerance can be an indication for AIP treatment.

Although surgical or endoscopic treatment is effective for pain control in symptomatic calcified chronic pancreatitis, it is still unknown whether early intervention in mild symptomatic pancreatic stones would reduce the frequency of acute exacerbation and improve long-term outcomes. The aim of this randomized-controlled trial was to explore the efficacy of early endotherapy for mild symptomatic pancreatic stones in comparison with the wait-and-see policy.Patients with mild symptoms because of pancreatic stones were assigned randomly to the endotherapy or the wait-and-see group. The wait-and-see group received endotherapy only when they developed refractory exacerbation or intractable pain. The primary outcome was the cumulative incidence of intolerable pain attacks and acute exacerbation. The secondary outcomes were the development of pancreatic insufficiency and the progression of pancreatic atrophy.A total of 20 patients were enrolled between March 2008 and March 2011. The study was terminated prematurely because of the poor patient enrollment. Early endotherapy tended to reduce the cumulative incidence of pain attacks and exacerbation, (P=0.17) with the composite incidence of pain attacks and exacerbation of 30% in the endotherapy group and 60% in the wait-and-see group. There were no significant differences in terms of diabetic status and the presence of steatorrhea. The thickness of the pancreas decreased significantly in the wait-and-see group (9.2-6.8 mm, P=0.041), but not in the endotherapy group (8.7-9.0 mm, P=0.60).In a small group of patients, early endotherapy in mild symptomatic chronic pancreatitis was associated with a trend toward a minor number of acute attacks and atrophy progression of the pancreas.

Objectives A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. Methods We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. Results A total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). Conclusions This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

Endoscopic ultrasound/ultrasonography‐guided biliary drainage (EUS‐BD) is a relatively new modality for biliary drainage after failed or difficult transpapillary biliary cannulation. Despite its clinical utility, EUS‐BD can be complicated by severe adverse events such as bleeding, perforation, and peritonitis. The aim of this paper is to provide practice guidelines for safe performance of EUS‐BD as well as safe introduction of the procedure to non‐expert centers. The guidelines comprised patient–intervention–comparison–outcome‐formatted clinical questions (CQs) and questions (Qs), which are background statements to facilitate understanding of the CQs. A literature search was performed using the PubMed and Cochrane Library databases. Statement, evidence level, and strength of recommendation were created according to the GRADE system. Four committees were organized: guideline creation, expert panelist, evaluation, and external evaluation committees. We developed 13 CQs (methods, device selection, supportive treatment, management of adverse events, education and ethics) and six Qs (definition, indication, outcomes and adverse events) with statements, evidence levels, and strengths of recommendation. The guidelines explain the technical aspects, management of adverse events, and ethics of EUS‐BD and its introduction to non‐expert institutions., Highlight Isayama and colleagues present the first clinical practice guidelines for endoscopic ultrasound‐guided biliary drainage (EUS‐BD), including indications, clinical results, procedures, devices and education. Their primary purpose is to improve the outcomes of EUS‐BD for biliary tract diseases by facilitating the safe introduction and performance of the procedure at non‐expert centers.

Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial sho...