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Endoscopic submucosal dissection (ESD) is globally performed to treat early epithelial tumors of the gastrointestinal tract, but delayed perforation is a problematic procedure-related complication. To address this problem, closure of ESD-induced mucosal defects with a detachable snare has been reported. However, one problem is that this method usually requires some degree of skill and replacing a single-channel scope with a two-channel scope. We developed the clip stopper closure (CSC) method using a detachable snare in combination with the ZEOCLIP, which can be easily performed with a single-channel scope, for ESD-induced mucosal defects. Six consecutive cases were treated with this closure method for colonic ESD-induced mucosal defects. The median closure time was 12.5 (10-24) min, and the success rate of this procedure was 100%. Our CSC method was able to be performed in any part of the colon. In conclusion, the CSC method using a detachable snare in combination with the ZEOCLIP is a simple but promising closure technique for ESD-induced mucosal defects.

Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis.

Although a large-caliber endoscope (LCE) is indispensable for through-the-scope placement of a self-expandable metallic stent (SEMS) in patients with malignant colonic obstruction (MCO), inaccessibility of the target obstructing lesion (TOL) by the endoscope is a significant cause of unsuccessful procedures. We herein present a novel salvage procedure when the TOL is not directly accessible by an LCE in conditions such as coexisting peritoneal carcinomatosis involving the colon. The salvage procedure, termed over-the-catheter endoscope replacement (OCER), starts with an ultraslim endoscope suitable for deep insertion beyond a tortuous colon for traversing a guidewire through the TOL. The ultraslim endoscope is then withdrawn and replaced by an LCE through the following steps. An endoscopic retrograde cholangiopancreatography catheter is preloaded in the LCE, the catheter alone is passed over the guidewire already traversed through the TOL, and the LCE is navigated over the catheter as far as possible toward the TOL to deliver the SEMS delivery system in a standard through-the-scope manner or further in an over-the-wire manner even if LCE insertion is incomplete. Among the 165 patients with MCO who underwent stenting during our study period, OCER led to successful procedures in all nine patients whose TOLs were initially inaccessible because of colon-involving peritoneal carcinomatosis. By utilizing the functions of distinctive endoscopes in a unique and complementary way, OCER can be a practical salvage option for challenging cases of MCO that are highly prone to unsuccessful palliation by conventional SEMS placement.

Background The C‐reactive protein : albumin ratio (CAR) has been reported as a novel prognostic marker in several cancers. The aim of this study was to investigate the prognostic value of CAR in patients with intrahepatic cholangiocarcinoma (ICC). Methods This was a single‐centre retrospective study of patients who underwent surgery for ICC in a university hospital in Japan between 1998 and 2018. CAR, Glasgow Prognostic Score (GPS) and modified GPS (mGPS) were calculated. Their correlation with recurrence‐free survival (RFS) and overall survival (OS) was analysed with Cox proportional hazards models. Results Seventy‐two patients were included in the study. Patients were divided into two groups according to the optimal CAR cut‐off value of 0·02. CAR above 0·02 was associated with higher carbohydrate antigen 19‐9 levels (20·5 versus 66·1 units/ml for CAR of 0·02 or less; P = 0·002), larger tumour size (3·2 versus 4·4 cm respectively; P = 0·031) and a higher rate of microvascular invasion (9 of 28 versus 25 of 44; P = 0·041). RFS and OS were shorter in patients with CAR above 0·02: hazard ratio (HR) 4·31 (95 per cent c.i. 2·02 to 10·63) and HR 4·80 (1·85 to 16·40) respectively. In multivariable analysis CAR above 0·02 was an independent prognostic factor of RFS (HR 3·29 (1·33 to 8·12); P, This study showed that a high C‐reactive protein : albumin ratio (CAR) is an independent predictor of poor recurrence‐free survival in patients with intrahepatic cholangiocarcinoma (ICC). The results also suggest that patients with ICC with a high CAR had a more aggressive tumour behaviour, including a larger tumour size, higher frequency of microvascular invasion and higher serum CA19‐9 concentration, than those with a low preoperative CAR. High CAR associated with poorer survival=E2=80=99

BACKGROUND The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) is controversial. AIM To compare the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs. METHODS We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs, which included eight hospitals in Fukuoka, Japan, between April 2001 and October 2017. A total of 142 patients with SNADETs treated with EMR or ESD were analyzed. Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups. We analyzed the treatment outcomes, including the rates of en bloc/complete resection, procedure time, adverse event rate, hospital stay, and local or metastatic recurrence. RESULTS Twenty-eight pairs of patients were created. The characteristics of patients between the two groups were similar after matching. The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group [median procedure time (interquartile range): 6 (3-10.75) min vs 87.5 (68.5-136.5) min, P < 0.001, hospital stay: 8 (6-10.75) d vs 11 (8.25-14.75) d, P = 0.006]. Other outcomes were not significantly different between the two groups (en bloc resection rate: 82.1% vs 92.9%, P = 0.42; complete resection rate: 71.4% vs 89.3%, P = 0.18; and adverse event rate: 3.6% vs 17.9%, P = 0.19, local recurrence rate: 3.6% vs 0%, P = 1; metastatic recurrence rate: 0% in both). Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation. CONCLUSION EMR has significantly shorter procedure time and hospital stay than ESD, and provides acceptable curability and safety compared to ESD. Accordingly, EMR for SNADETs is associated with lower medical costs.

Acquiring adequate attached mucosa is important in restoring masticatory function with a removable dental prosthesis or dental implant. In patients with inadequate attached mucosa, a free gingival graft (FGG) with a custom stent is used. However, it is challenging to apply the conventional method for fabricating a stent with a reshaped cast in patients with reconstructed mandibles because the reconstructed mandible has limitations due to a titanium mesh, skin flap, and unique bone morphology. In the present report, we have proposed a new design and fabrication process for a mucocompressive splint via medical engineering to acquire the attached mucosa for the prosthodontic treatment of reconstructed mandibles.Three-dimensional (3D) craniomandibular models were reconstructed from a computed tomography dataset after mandibular reconstruction. The dentition region was replaced with highly precise scan data of the dental casts using a 3D scanner. The alveolar ridge mucosa and teeth were ideally designed using the 3D model while referring to the anatomical structures. The jig used to fabricate the working dental cast with artificial gum in real space was designed and fabricated using a 3D printer. The alveolar ridge was altered into a simulated configuration on the articulator using a jig. A mucocompressive splint was fabricated on an altered dental cast. The splint was immediately seated on the mandible without any major adjustments after the FGG.Adequate attached mucosa for the prosthodontic treatment of a reconstructed mandible was obtained by the pre-surgical fabrication of a mucocompressive splint through medical engineering.

Recently, endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) procedures have been gradually established; nonetheless, some adverse events (AEs) have been reported. Dilation procedures using a non-cautery or cautery device increase the incidence of AEs in EUS-HGS.We evaluated EUS-HGS procedures without dilation and the factors associated with dilation.We enrolled 79 patients who underwent EUS-HGS between July 2015 and March 2021 at two centers, 72 of whom had technical success (72/79, 91%). During the EUS-HGS procedures, we defined patients without dilation procedures as the dilation (-) group. We divided the patients into two groups: the dilation (+) (35 patients) and dilation (-) (37 patients) groups. We performed a propensity score matching analysis to adjust for confounding bias between the two groups. Multivariable logistic regression analysis was conducted to identify factors associated with dilation.There was no difference in clinical success rate between the dilation (+) and dilation (-) groups (91% vs. 95%, P = 0.545). The AE rate (P = 0.013) and long procedure time (P = 0.017) were significantly higher in the dilation (+) group than in the dilation (-) group before and after propensity score matching. Factors associated with dilation were plastic stent placement (odds ratio [OR], 6.96; 95% confidence interval [CI], 1.68-28.7; P = 0.007) and puncture angle of ≤ 90° (OR, 44.6; 95% CI, 5.1-390; P 0.001).A dilation procedure in EUS-HGS may not always be necessary. However, patients with an angle of ≤ 90° between the needle and intrahepatic biliary tract or plastic stent deployment require dilation procedures.

Traditionally, removable partial dentures (RPDs) have been made by using an elastic impression material and casting from a framework wax pattern on a refractory cast. In this short communication, the procedures for digitally fabricating removable partial dentures using an intraoral scanner (IOS) and additive manufacturing system (AM) are described. The adaptation accuracy of the RPD using IOS and AM techniques was evaluated subjectively as good or satisfactory.

Background/Aims: Patients with acute cholecystitis (AC) after metallic stent (MS) placement for malignant biliary obstruction (MBO) have a high surgical risk. We performed percutaneous transhepatic gallbladder aspiration (PTGBA) as the first treatment for AC. We aimed to identify the risk factors for AC after MS placement and the poor response factors of PTGBA.Methods: We enrolled 401 patients who underwent MS placement for MBO between April 2011 and March 2020. The incidence of AC was 10.7%. Of these 43 patients, 37 underwent PTGBA as the first treatment. The patients’ responses to PTGBA were divided into good and poor response groups.Results: There were 20 patients in good response group and 17 patients in poor response group. Risk factors for cholecystitis after MS placement included cystic duct obstruction (p

Background: Adult T-cell leukemia/lymphoma (ATLL) frequently involves the gastrointestinal (GI) tract, and patients mainly show an aggressive clinical course despite of intensive cytotoxic treatments. We investigated the characteristic clinicopathological and endoscopic features of GI ATLL. Methods: This was a retrospective analysis of 61 GI tract lesions in 54 ATLL patients. Results: Thirty-six (67%) patients were classified as having lymphoma-type ATLL and 18 (33%) patients were classified as having acute-type with leukemic changes. Examined ATLL lesions in the stomach and intestine (small intestine and colorectum) were 40 (66%) and 21 (34%), respectively. Gastric ATLL lesions were frequently found in the lymphoma-type (29/38; 76%) compared with the acute-type lesions (11/23; 48%; P=0.023). Intestinal ATLL lesions were frequent in the acute-type (12/23; 52%) compared with the lymphoma-type lesions (9/38; 24%; P=0.023). Endoscopically, tumor-forming type lesions were significantly more frequent in lymphoma-type ATLL lesions (29/38 lesions; 76%) compared with acute-type lesions (10/23; 44%; P=0.0096). The superficial spreading-type was significantly more frequent in acute-type lesions (12/23 lesions; 52%) compared with lymphoma-type lesions (3/38; 8%; P=0.0003). Additionally, gastropathy-, enteropathy-, or proctocolitis-like lesions were distinct features, mainly in the acute type (9/23 lesions; 39%). Twenty three of 39 tumor-forming-type lesions (59%) were significantly composed of pleomorphic or anaplastic large cell lymphoma, and 13 of 15 superficial spreading-type lesions (87%) were significantly composed of pleomorphic medium-sized cells (P=0.007, in each). Six patients (11%) who were estimated as having primary GI ATLL based on restricted clinical stages, showed a significantly better overall survival (OS) compared with the 48 advanced-stage patients (P=0.017). Twenty patients with solitary tumor-forming-type lesions showed a significantly better OS than 17 patients with the multiple tumor-forming-type (P=0.015) and five with the mucosal-thickening-type lesions (P=0.04). Twenty-six patients with pleomorphic or anaplastic large cell ATLL showed a significantly better prognosis compared with 28 patients with pleomorphic medium-sized ATLL (P=0.034). Conclusions: ATLL predominantly involves the stomach. Leukemic behavior of ATLL had a large influence on the tumor location and endoscopic features of GI tract lesions. Gastropathy-, enteropathy-, and proctocolitis-like lesions showed additional distinct characteristics. Primary GI ATLL in the early clinical stages, solitary tumor-forming-type lesions and large tumor cells showed better prognostic factors than other factors, respectively.

Objectives This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. Methods This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. Results A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3% vs 70.8%, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). Conclusions The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern.

Cholangitis is a major complication following transplantation. We report a living donor liver transplant (LDLT) patient with cholangitis due to multiple stones in the intrahepatic bile duct during hepaticojejunostomy anastomosis, who was successfully treated with the rendezvous technique using double balloon endoscope. A 64-year-old woman underwent LDLT with right lobe graft and hepaticojejunostomy for Wilson disease. There was bile leakage with biliary peritonitis, which was treated conservatively after transplant. Two years after surgery, she developed reiterated cholangitis due to stenosis of hepaticojejunostomy anastomosis and multiple stones in the intrahepatic bile ducts. Percutaneous transhepatic biliary drainage was performed. The size of the drainage tube was increased, and the anastomotic area was dilated in a stepwise manner using a balloon catheter. The stones were crushed and lithotomy was performed using electronic hydraulic lithotripsy through cholangioscopy. Finally, lithotomy was performed for the remaining stones through endoscopic retrograde cholangiography with the rendezvous technique using the double balloon endoscope. Rendezvous approach with percutaneous transhepatic biliary drainage and double balloon endoscopic retrograde cholangiography was an effective treatment for the multiple intrahepatic stones in hepaticojejunostomy following LDLT with right lobe graft.

Background Cold polypectomy has been increasingly used to remove diminutive colorectal polyps. We evaluated the local recurrence rate of diminutive polyps at the 1-year follow-up after cold forceps polypectomy (CFP). Methods In a prospective, multicenter, observational cohort study, patients with diminutive colorectal polyps ( ≤ 5 mm) were treated by CFP using jumbo forceps followed by magnified narrow-band imaging (NBI). Patients were assessed for local recurrence at 1-year follow-up. Risk factors associated with local recurrence were analyzed using logistic regression analysis. Results Overall, 955 lesions were resected in 471 patients who completed the 1-year follow-up. The endoscopic complete resection rate was 99.4 %. Immediate and delayed bleeding occurred in 0.8 % and 0.2 % of cases, respectively, with no perforations observed. Local recurrence occurred in 2.1 % of cases at the 1-year follow-up. Univariable analyses indicated that polyps > 3 mm (P 3 mm were significantly associated with local recurrence (odds ratio 3.4, P = 0.02). Conclusions CFP with jumbo forceps followed by NBI-magnified observation had a low local recurrence rate and is an acceptable therapeutic option for diminutive colorectal polyps. Although we recommend limiting the use of CFP with jumbo forceps to polyps ≤ 3 mm in size, future comparative studies are needed to make recommendations on cold polypectomy using either forceps or snares as the preferred approach for diminutive polyp resection.

Vonoprazan is a potassium competitive acid blocker used to treat erosive gastroesophageal reflux disease (GERD) with stronger, more stable acid-suppressing effects than proton pump inhibitors (PPIs). This study clarified the usefulness and superiority of vonoprazan administered every second day over PPIs in the maintenance therapy of erosive GERD.This is a prospective, multicenter, open-label, two-period randomized cross-over study. Patients were randomized to either the vonoprazan-lansoprazole (VP-LZ) group, who were given vonoprazan 10 mg for the first 4 weeks and then lansoprazole 15 mg for the next 4 weeks both administered once every second day, or the lansoprazole-vonoprazan (LZ-VP) group, who were treated in reverse. GERD symptoms were compared using symptom diaries, the frequency scale for symptoms of GERD (FSSG), and the gastrointestinal symptom rating scale (GSRS).We enrolled 122 patients between December 2017 and May 2019. Symptoms were well controlled in vonoprazan administration and lansoprazole administration were 93.6% and 82.1%, respectively, with a significant difference on McNemar's test (P = 0.003). During the second 4 weeks, 94.4% and 76.7% of patients in the VP-LZ and LZ-VP groups, respectively, were well controlled following for ≥ 6 consecutive days a week (P = 0.009). During the first 4 weeks, 96.7% and 80.0% of patients were well controlled with 1 weekly in the VP-LZ and LZ-VP groups, respectively, during the first 4 weeks (P = 0.007). GERD symptoms, assessed via FSSG and GSRS, significantly decreased with vonoprazan administration once every second day.Vonoprazan administered once every second day could be an effective alternative to PPIs in the maintenance treatment of erosive GERD (UMIN000030393).

A 76-year-old woman suffered from repeated postprandial syncope of unknown cause. Computed tomography scanning revealed an enlarged hiatal hernia sac with food residues that compressed both the left atrium and inferior vena cava. As soon as the hernia cavity expanded during an upper gastrointestinal X-ray examination, she experienced a deterioration of her level of consciousness. Therefore, we diagnosed her of a swallow syncope due to left atrium compression by the huge hernia sac. The sac also compressed the inferior vena cava, and she experienced a transient elevation of her hepatobiliary enzyme level probably due to the influence of the congestive liver. Thus, clinicians should always keep this condition in mind when encountering patients with post-meal syncope.

Background Colorectal T/natural killer (NK)-cell lymphomas (TNKCL) are very rare. Endoscopic and clinicopathological characteristics of colorectal TNKCL have not been clearly demonstrated. In this study, we demonstrated the clinical characteristics of colorectal TNKCL. Methods Endoscopic and clinicopathological characteristics were investigated in 27 patients with colorectal monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), adult T-cell leukemia/lymphoma (ATLL), and other types of TNKCL. Results Nine TNKCL patients (33%) were classified as MEITL, 11 (41%) as ATLL, and seven (26%) as other. Four patients with Epstein-Barr Virus-positive (EBV+) TNKCL, two indolent T-cell lymphoproliferative disorder and one anaplastic large cell lymphoma were included in the other group. Endoscopically, six MEITL (67%) and five ATLL (46%) showed diffuse-infiltrating type, in which the main endoscopic lesion was edematous mucosa in MEITL, while aphthoid erosion and edematous mucosa were typical in ATLL. Ulcerative type was identified in four other group patients (57%), including two EBV+ TNKCL. An increase in atypical T-intraepithelial lymphocytes (T-IELs) was noted in seven MEITL (88%) and six ATLL (60%) patients, but not in the other group (0%) patients. Five MEITL patients (56%) showed features of lymphocytic proctocolitis with increased CD8+ T-IELs. Conclusions MEITL and ATLL occasionally invaded the colorectum, and primary involving MEITL was observed. Diffuse infiltrating type was the characteristic endoscopic finding in colorectal MEITL and ATLL, while ulcerative type was observed in the other group. Features of lymphocytic proctocolitis may be prodromal findings of MEITL.

Background Sarcopenia is an independent predictor of death after living-donor liver transplantation (LDLT). However, the ability of the Asian Working Group for Sarcopenia criteria for sarcopenia (defined as reduced skeletal muscle mass plus low muscle strength) to predict surgical outcomes in patients who have undergone LDLT has not been determined. Methods This study prospectively enrolled 366 patients who underwent LDLT at Kyushu University Hospital. Skeletal muscle area (determined by computed tomography), hand-grip strength, and gait speed were measured in 102 patients before LDLT. We investigated the relationship between sarcopenia and surgical outcomes after LDLT performed in three time periods. Results The number of patients with lower skeletal muscle area has increased to 52.9% in recent years. The incidence of sarcopenia according to the Asian Working Group for Sarcopenia criteria was 23.5% (24/102). Patients with sarcopenia (defined by skeletal muscle area and functional parameters) had significantly lower skeletal muscle area and weaker hand-grip strength than did those without sarcopenia. Compared with non-sarcopenic patients, patients with sarcopenia also had significantly worse liver function, greater estimated blood loss, greater incidence of postoperative complications of Clavien-Dindo grade IV or greater (including amount of ascites on postoperative day 14, total bilirubin on postoperative day 14, and postoperative sepsis), and longer postoperative hospital stay. Multiple logistic regression analysis revealed sarcopenia as a significant predictor of 6-month mortality. Conclusions The combination of skeletal muscle mass and function can predict surgical outcomes in LDLT patients.

Thrombectomy is a routine or common practice for treating organized portal vein thrombosis (PVT) during liver transplantation. However, this procedure is often performed in a blinded fashion and can result in insufficient thrombectomy or devastating consequences such as injury to the retropancreatic portal vein where prompt repair is very difficult. To overcome these drawbacks for blind thrombectomy, we herein describe a new technique that makes complex thrombectomy safe and easy under direct ultrasound vision. This procedure is readily available and highly reproducible and can be used as the standard procedure for treating extensive PVT.

A 51-year-old woman underwent endoscopic biliary drainage with a plastic stent for obstructive jaundice due to unresectable pancreatic head cancer. During chemotherapy following heavy ion therapy for the cancer, she presented with acute cholangitis and massive rectal bleeding. The massive hemorrhage was caused by rupture of the biliary duct due to a pseudoaneurysm in the right hepatic artery. The position of the aneurysm coincided with the liver-side end of the plastic stent. Sustained irritation of the arterial and bile duct walls by the stent was considered to have contributed to formation of the aneurysm.

Background/Aims: Delayed bleeding is among the adverse events associated with therapeutic gastrointestinal endoscopy. The aim of this study was to evaluate risk factors for delayed bleeding after gastrointestinal endoscopic resection in patients receiving oral anticoagulants as well as to compare the rates of occurrence of delayed bleeding between the oral anticoagulants used. Methods: We retrospectively analyzed a total of 772 patients receiving anticoagulants. Of these, 389 and 383 patients were receiving direct oral anticoagulants (DOACs) and warfarin, respectively. Therapeutic endoscopic procedures performed included endoscopic submucosal dissection (ESD), endoscopic mucosal resection, polypectomy, and cold polypectomy. Results: Delayed bleeding occurred in 90 patients (11.7%) with no significant difference between the DOAC and warfarin groups (9.5 and 13.8%, respectively). Delayed bleeding occurred significantly more frequently with apixaban than with rivaroxaban (13.5 vs. 6.4%; p < 0.05). A multivariate analysis identified continued anticoagulant therapy (OR 2.29), anticoagulant withdrawal with heparin bridging therapy (HBT; OR 2.18), anticoagulant therapy combined with 1 antiplatelet drug (OR 1.72), and ESD (OR 3.87) as risk factors for delayed bleeding. Conclusion: This study identified continued anticoagulant therapy, anticoagulant withdrawal with HBT, anticoagulant therapy combined with 1 antiplatelet drug, and ESD as risk factors for delayed bleeding after therapeutic endoscopy in patients receiving oral anticoagulants. Delayed bleeding rates were not significantly different between those receiving DOACs and warfarin. It was also suggested that the occurrence of delayed bleeding may vary between different DOACs and that oral anticoagulant withdrawal should be minimized during therapeutic gastrointestinal endoscopy, given the thromboembolic risk involved.

T helper (Th) and regulatory T (Treg) cell-related cytokines are implicated in inflammatory bowel diseases, including ulcerative colitis (UC). While these cytokines are generally upregulated in inflamed mucosae, the key cytokine profile explaining disease severity has not been determined. The Rachmilewitz endoscopic index (REI) was assessed in 61 UC patients undergoing colonoscopy. Biopsies obtained from inflamed (REI 3–12) and noninflamed (REI 0–2) areas were analyzed by quantitative PCR for expression of mRNAs encoding cytokines and transcription factors related to Th1 (TNF-α, IFN-γ, IL-12p35, IL-12p40, and T-bet), Th2 (IL-4, IL-13, IL-33, and GATA3), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23p19, IL-6, and RORC), Th9 (IL-9, IRF4, and PU.1), and Treg (TGF-β and Foxp3). Expression patterns associated with higher REI were determined by univariate and multivariate analyses. Despite general upregulation, none of these mRNAs showed univariate correlation with REI in inflamed samples. Multiple regression analysis, however, found that joint expression of IL-17A, IL-17F, IL-21, RORC, and TGF-β was significantly predictive of REI (P

Although Roux-en Y hepaticojejunostomy was previously recommended for the biliary reconstruction in liver transplantation for primary sclerosing cholangitis (PSC), some recent reports showed no difference in the graft survival between Roux-en Y and duct-to-duct anastomosis in deceased-donor liver transplantation. On the other hand, considering the risk of recurrence and the short length of the bile duct of the graft, duct-to-duct biliary anastomosis has never been reported in a patient undergoing living-donor liver transplantation (LDLT) for PSC. A 45 year-old male underwent LDLT using a left-lobe graft donated from his brother. Cholangiography showed no lesion in his common bile duct and duct-to-duct anastomosis was chosen for him. Fifteen months later, he suffered cholangitis due to PSC recurrence and endoscopic retrograde cholangiography was performed. The stents were inserted into his B2 and B3, and he remains well. Because of the ability to easily manage biliary complication, duct-to-duct biliary reconstruction may become the first choice in LDLT for PSC without common bile duct lesions.

Background T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. Methods The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. Results Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). Conclusions The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.

Introduction The first drug selected for treatment of gastro-oesophageal reflux disease (GERD) and prevention of the recurrence is a proton pump inhibitor (PPI), but recently, a potassium-competitive acid blocker (P-CAB) was put on the market in Japan. Its onset of effect is faster than PPI, and it takes more than 2 days to recover acid secretion after the withdrawal period. Therefore, unlike PPI, the usefulness of every other day administration or discontinuous administration is expected. Methods and analysis This study is a prospective, multicentre, open-label, two-period randomised cross-over study to compare the efficacy and safety of PPI every other day administration and P-CAB every other day administration in 120 patients who receive erosive GERD maintenance therapy with PPI. Patients will be randomly allocated to receive 4 weeks P-CAB or PPI followed by 4 weeks cross over, where those on P-CAB will receive PPI and vice versa. The primary endpoint is proportion of asymptomatic patients. Secondary endpoints are suppressive effect of GERD symptoms, proportion of asymptomatic patients at each time point, safety and cost-saving effect of P-CAB every other day administration, compliance with every other day administration, and proportion of asymptomatic patients at the first month of study drug administration. Ethics and dissemination This study was approved by the National Hospital Organization Central Review Board for Clinical Trials (5 December 2017). Discussion If P-CAB every other day administration is established as one of GERD maintenance therapies, there is merit in both medical cost reduction and the safety to alleviate elevation in serum gastrin. Trial registration number UMIN000034701.

Background Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). Methods A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. Results Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. Conclusions Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a rare but severe complication after liver transplantation. In contrast to other thrombotic microangiopathies, treatment for TA-TMA has yet to be clarified. A 52-year-old male patient with liver cirrhosis due to hepatitis C underwent split liver transplantation from a deceased donor. His clinical course was without complication until 4 days after transplantation, when he experienced impaired consciousness, hemolytic anemia with fragmented erythrocytes, and marked thrombocytopenia. TA-TMA was diagnosed, and recombinant thrombomodulin was administered for 4 days. The patient's clinical symptoms and laboratory data rapidly improved. He has been followed up for 6 months and has not shown any complications. The pathogenesis of TA-TMA is endothelial damage in the vasculature. Recombinant thrombomodulin, an endothelial cell-protecting agent, is a promising new therapeutic choice for TA-TMA after liver transplantation.

Large-for-size syndrome (LFSS) is controversial in pediatric living donor liver transplantation patients and is associated with a poor graft outcome. Similar situations in deceased donor liver transplantation (DDLT) in adults have not been reported frequently, and there are no official guidelines worldwide. Deceased donation is extremely limited in Japan, and when a larger liver is allocated for a very sick small recipient in Japan, transplantation with a plan to address LFSS might be necessary. The patient is a 58-year-old female patient who had acute liver failure with coma. The graft-recipient weight ratio (GRWR) was 2.74%. Although the graft was enlarged by reperfusion, the intraoperative Doppler ultrasound, performed after reperfusion, showed sufficient graft in-flow and out-flow. However, when the liver graft was situated appropriately into the right phrenic space supported by the rib cage and diaphragm, the blood flow in the hepatic vein and portal vein was significantly reduced. Graft blood flow did not improve without removing it from the right subphrenic space. Therefore, we decided to perform an in situ graft posterior segmentectomy, so that the graft right lobe was properly accommodated in the patient's right subphrenic space. After the segmentectomy of the graft, an intraoperative Doppler sonogram showed significantly improved blood flow. LFSS could be a significant operative challenge in adult DDLT, especially in areas with limited chances of DDLT. In situ posterior segmentectomy in the demarcated area could be a solution for treating patients with LFSS.

We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea. We diagnosed immune-related colitis and started oral prednisolone. However, the steroid therapy was ineffective, so the patient was administered infliximab and an increased dose of prednisolone. Her symptoms subsequently resolved, and her mucosal lesions improved. Six months after the last administration of nivolumab, osimertinib was initiated as fourth-line therapy, but 3 days later, the patient developed blood in the stool and frequent diarrhea. Osimertinib treatment was discontinued, given the possibility that it had reactivated the patient’s immune-related colitis. We subsequently re-administered oral prednisolone (2 mg/kg/day), and the colitis resolved within a few weeks.

We read with great interest the article by Kwon et al from Asan Medical Center (1). The authors presented outcomes of living donor liver transplantation (LDLT) for septuagenarians with a 5-year survival rate of 69.8% and concluded that they should not be excluded from LDLT. On the other hand, at Kyushu University, we have indicated different graft and recipient selection strategies of LDLT for elderly recipients ≥ 65 years with 89.9% for 5-year survival rate (2). We have performed 12 LDLTs for septuagenarian patients (1.8%) out of 670 LDLTs between October 1996 and May 2017. In this article, we compare strategies and outcomes of LDLT for septuagenarians in terms of the balance between donor risks and recipient benefits (3). This article is protected by copyright. All rights reserved.

Background Management of anticoagulants for patients undergoing polypectomy is still controversial. Cold snare polypectomy (CSP) is reported to cause less bleeding than hot snare polypectomy (HSP). Objective To compare outcomes between continuous administration of anticoagulants (CA) with CSP (CA+CSP) and periprocedural heparin bridging (HB) with HSP (HB+HSP) for subcentimeter colorectal polyps. Design Multicenter, parallel, noninferiority randomized controlled trial. (University Hospital Medical Information Network Clinical Trials Registry: UMIN000019355). Setting 30 Japanese institutions. Patients Patients receiving anticoagulant therapy (warfarin or direct oral anticoagulants) who had at least 1 nonpedunculated subcentimeter colorectal polyp. Intervention Patients were randomly assigned to undergo HB+HSP or CA+CSP and followed up 28 days after polypectomy. Measurements The primary end point was incidence of polypectomy-related major bleeding (based on the incidence of poorly controlled intraprocedural bleeding or postpolypectomy bleeding requiring endoscopic hemostasis). The prespecified inferiority margin was -5% (CA+CSP vs. HB+HSP). Results A total of 184 patients were enrolled: 90 in the HB+HSP group, 92 in the CA+CSP group, and 2 who declined to participate after enrollment. The incidence of polypectomy-related major bleeding in the HB+HSP and CA+CSP groups was 12.0% (95% CI, 5.0% to 19.1%) and 4.7% (CI, 0.2% to 9.2%), respectively. The intergroup difference for the primary end point was +7.3% (CI, -1.0% to 15.7%), with a 0.4% lower limit of 2-sided 90% CI, demonstrating the noninferiority of CA+CSP. The mean procedure time for each polyp and the hospitalization period were longer in the HB+HSP than in the CA+CSP group. Limitation An open-label trial assessing 2 factors (anticoagulation approach and polypectomy procedure type) simultaneously. Conclusion Patients having CA+CSP for subcentimeter colorectal polyps who were receiving oral anticoagulants did not have an increased incidence of polypectomy-related major bleeding, and procedure time and hospitalization were shorter than in those having HB+HSP. Primary funding source Japanese Gastroenterological Association.

Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV-positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared retrospectively with unmodified peg-IFN/ribavirin therapy (standard group). Association of host- or virus-related factors with sustained virological response was assessed. In HCV replicon cells, the effects of pitavastatin and/or EPA on HCV replication and expression of innate-immunity- and lipid-metabolism-associated genes were investigated. In patients infected with HCV-1b, sustained virological response rates were significantly higher in the add-on than standard group. In both groups, sustained virological response rates were significantly higher in patients with genotype TT of IL-28B (rs8099917) than in those with non-TT genotype. Among the patients with non-TT genotype, sustained virological response rates were markedly higher in the add-on than standard group. By multivariate analysis, genome variation of IL28B but not add-on therapy remained as a predictive factor of sustained virological response. In replicon cells, pitavastatin and EPA suppressed HCV replication. Activation of innate immunity was obvious in pitavastatin-treated cells and EPA suppressed the expression of sterol regulatory element binding protein-1c and low-density lipoprotein receptor. Addition of pitavastatin and EPA to peg-IFN/ribavirin treatment improved sustained virological response in patients infected with HCV-1b. Genotype variation of IL-28B is a strong predictive factor in add-on therapy.