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We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF).This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF.Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor.Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

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.

An 84-year-old man was referred to our hospital for a cystic lesion of the pancreatic head, swelling of the pancreatic tail and hilar biliary stricture, resulting in elevated liver enzyme levels. We suspected branch duct-type intraductal papillary mucinous neoplasm (IPMN) and type I autoimmune pancreatitis (AIP) associated with sclerosing cholangitis because of the high serum IgG4 levels. The main pancreatic duct on the tail side of the AIP lesion was moderately dilated. Although the biliary stricture and pancreatic swelling improved after prednisolone treatment, the pancreatic enzyme levels increased rapidly. The entire main pancreatic duct exhibited remarkable dilatation, which led to the diagnosis of mixed-type IPMN. The clinical characteristics of IPMN in the main pancreatic duct appear to have been initially masked by AIP.

To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted.Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire.The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis.The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases.

Covered self-expandable metal stent (cSEMS) for gastric outlet obstruction (GOO) has been developed to overcome tumor ingrowth but is prone to be associated with an increased risk of migration. Clinical impact of the novel large-bore cSEMS for malignant GOO remains unclear.A total of 117 patients undergoing endoscopic cSEMS placement for malignant GOO were enrolled in this multicenter retrospective study. Technical and clinical success, adverse events, recurrent GOO, and survival after stent placement were compared between 24 mm-cSEMS (n = 49) and 20 mm-cSEMS (n = 68).Patient characteristics were well-balanced and thus similar survival was observed between the two groups (136 days vs. 89 days, P = 0.60). Technical success rate of 100% and clinical success rate of 96% were achieved both in 24 mm-cSEMS and 20 mm-cSEMS, respectively. The median cumulative time to recurrent GOO was significantly longer in 24 mm-cSEMS than in 20 mm-cSEMS (380 days vs. 138 days, P = 0.01). The incidence of adverse events and recurrent GOO was comparable: 12% vs. 15% (P = 0.91), and 16% vs. 31% (P = 0.11); however, no stent migration was observed in 24 mm-cSEMS. In a subgroup analysis, the superiority of 24 mm-cSEMS to 20 mm-cSEMS was demonstrated in extrinsic cancers (380 days vs. 121 days, P = 0.01) but not in intrinsic cancers (151 days vs. not reached, P = 0.47).The 24 mm-cSEMS may improve time to recurrent GOO with ensuring acceptable safety in patients with malignant GOO.

Summary Background IgG4-related disease is a newly recognised immunopathological entity that includes autoimmune pancreatitis, IgG4-related sialadenitis, and IgG4-related kidney disease. To understand the genetic landscape of IgG4-related disease, we did a genome-wide association study. Methods We did a genome-wide association study of Japanese individuals, initially screening 857 patients with IgG4-related disease at 50 Japanese research institutions and DNA samples from 2082 healthy control participants from the Nagahama Prospective Genome Cohort for the Comprehensive Human Bioscience. From Oct 27, 2008, to July 22, 2014, we enrolled 835 patients and used data from 1789 healthy participants. Only patients with confirmed diagnosis of IgG4-related disease according to the international diagnostic criteria were included. Genotyping was done with the Infinium HumanOmni5Exome, HumanOmni2.5Exome, or HumanOmni2.5 Illumina arrays, and genomic distributions were compared between case and control samples for 958 440 single nucleotide polymorphisms. The HLA region was extensively analysed using imputation of HLA alleles and aminoacid residues. Fine mapping of the FCGR2B region was also done. Associations between clinical manifestations of disease and the genetic variations identified in these two genes were examined. Findings We identified the HLA-DRB1 (p=1·1×10−11) and FCGR2B (p=2·0×10−8) regions as susceptibility loci for IgG4-related disease. We also identified crucial aminoacid residues in the β domain of the peptide-binding groove of HLA-DRB1, in which the seventh aminoacid residue showed the strongest association signal with IgG4-related disease (p=1·7×10−14), as has been reported with other autoimmune diseases. rs1340976 in FCGR2B showed an association with increased FCGR2B expression (p=2·7×10−10) and was in weak linkage disequilibrium with rs1050501, a missense variant of FCGR2B previously associated with systemic lupus erythematosus. Furthermore, rs1340976 was associated with the number of swollen organs at diagnosis (p=0·011) and IgG4 concentration at diagnosis (p=0·035). Interpretation Two susceptibility loci for IgG4-related disease were identified. Both FCGR2B and HLA loci might have important roles in IgG4-related disease development. Common molecular mechanisms might underlie IgG4-related disease and other immune-related disorders Funding The Japanese Ministry of Health, Labour, and Welfare, the Japanese Agency of Medical Research and Development, and Kyoto University Grant for Top Global University Japan Project.

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.

Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP.Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation.Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones.The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.

BACKGROUND Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.

Early identification of severe disease of acute pancreatitis (AP) is of critical importance to improve the prognosis. Fluid sequestration (FS), calculated from administrated fluid and fluid output, is a simple prognostic parameter. We examined its utility in the early phase of AP. We retrospectively investigated AP patients between January 2009 and April 2017. We compared FS in the first 24 h (FS24) with FS in the first 48 h (FS48) and administrated fluid volume within the first 24 h (FV24). Diagnostic yield for predicting intensive care unit (ICU) admission and persistent organ failure (POF) was assessed using receiver operating characteristic curves. We also evaluated risk factors for developing severe disease of AP. A total of 400 AP patients were included in the analysis (median age 64 years; male 60%). According to the Japanese severity criteria, 158 patients (40%) were diagnosed as severe disease. The rates of mortality, ICU admission and POF were 0.8%, 4.5% and 7.3%, respectively. FS24 showed a similar predictive accuracy in comparison with FS48 and was superior to FV24 in predicting ICU admission and POF. FS24 ≥ 1.6 L, male sex, presence of systemic inflammatory response syndrome and computed tomography severity index ≥ 3 on admission were independent risk factors for disease progression in AP in the multivariate analysis. FS24 was a simple and easily calculated parameter with high predictive accuracy for discriminating patients who needed intensive care. Patients with FS24 ≥ 1.6 L had an increased risk of developing severe disease.

Type 1 autoimmune pancreatitis (AIP) is histologically characterized by lymphoplasmacytic sclerosing pancreatitis (LPSP). Recently, the diagnostic yield of endoscopic ultrasonography-guided fine needle aspiration/biopsy (EUS-FNA/B) for AIP has been reported. However, its role in the diagnostic flow of AIP is not fully elucidated. We retrospectively reviewed 53 consecutive patients who were suspected with AIP and underwent EUS-FNA/B. We evaluated the contribution of EUS-FNA/B to the diagnosis of AIP before considering response to steroid therapy among patients with diffuse enlargement of the pancreas and those with focal enlargement, respectively. Twenty-two patients showed diffuse pancreatic enlargement and 31 showed focal enlargement. The final diagnosis was definitive AIP in 32 patients, probable AIP in 2, possible AIP in 1, and mass-forming focal pancreatitis in 18. There was no change in diagnosis after EUS-FNA/B among patients with diffuse pancreatic enlargement, while diagnosis changed in 38.7% (12/31) among those with focal enlargement&mdash, there was a probable to definitive diagnosis in 4 patients, unspecified to definitive in 3, and unspecified to probable in 5. EUS-FNB provided a significantly higher sensitivity for typical pathological findings of LPSP than EUS-FNA, and 10 patients were diagnosed as pathologically definitive AIP by EUS-FNB, though none were by EUS-FNA (p = 0.002). EUS-FNA/B was useful in the diagnosis of focal type AIP, and steroid therapy could be introduced after the diagnosis was confirmed. Meanwhile, EUS-FNA/B provided no contribution to diagnosis of diffuse type AIP. EUS-FNB showed a higher diagnostic yield than FNA.

Exocrine pancreatic insufficiency may impair the nutritional status in pancreatic cancer (PC), but the role of pancreatic enzyme replacement therapy (PERT) is not fully evaluated. Therefore, we conducted this multicenter open-label randomized controlled trial to evaluate the role of PERT in PC patients.Patients with unresectable PC receiving chemotherapy were randomly assigned to pancrelipase and nonpancrelipase groups. Patients in the pancrelipase group took oral pancrelipase of 48,000 lipase units per meal. N-benzoyl-tryrosyl para-aminobenzoic acid (NBT-PABA) test was performed at baseline. Our primary endpoint was change in body mass index (BMI) at 8 weeks. Secondary endpoints were change in other nutritional status at 8 weeks and overall survival.A total of 88 patients were enrolled between May 2014 and May 2016. The NBT-PABA test was lower than the normal range in 90%. There were no significant differences in change in BMI at 8 weeks: 0.975 and 0.980 in the pancrelipase and the nonpancrelipase groups, respectively (P = 0.780). The other nutritional markers were also comparable. The median overall survival was 19.0 and 12.0 months (P = 0.070).In this randomized controlled trial, pancrelipase failed to improve the change in BMI at 8 weeks in PC patients receiving chemotherapy.

BACKGROUND AND AIM Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting. METHODS A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied. RESULTS Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis. CONCLUSIONS Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Although patients with pancreatic cancer (PC) are prone to exocrine pancreatic insufficiency, there are little evidence about pancreatic enzyme replacement therapy (PERT) in patients with PC, especially those receiving chemotherapy.This is a prospective consecutive observational study of PERT in patients with unresectable PC. We prospectively enrolled patients receiving chemotherapy for unresectable PC from April 2012 to February 2014 and prescribed oral pancrelipase of 48,000 lipase units per meal (pancrelipase group). N-benzoyl-tryrosyl para-aminobenzoic acid test was performed at baseline. Patients receiving chemotherapy before April 2012 were retrospectively studied as a historical cohort. Data on the nutritional markers at baseline and 16 weeks were extracted, and serial changes, defined as the ratio of markers at 16 weeks/baseline, were compared between 2 groups.A total of 91 patients (46 in the pancrelipase group and 45 in the historical cohort) were analyzed. N-benzoyl-tryrosyl para-aminobenzoic acid test was low in 94% of the pancrelipase group. Serial change in the pancrelipase group versus historical cohort was 1.01 versus 0.95 in body mass index (P0.001) and 1.03 versus 0.97 in serum albumin (P = 0.131).The rate of exocrine pancreatic insufficiency in unresectable PC was high, and PERT can potentially improve the nutritional status during chemotherapy.

Aim Primary sclerosing cholangitis (PSC) is a rare cholestatic disease. We previously reported the effects of bezafibrate on elevated hepatobiliary enzyme levels in patients with this disease both retrospectively and prospectively. In this study, we assessed factors predictive of bezafibrate efficacy. Methods Twenty-five patients with PSC, who underwent bezafibrate therapy (400 mg per day) from November 2006 to June 2015, were evaluated. Treatment was judged as being effective if the levels of all of the hepatobiliary enzymes decreased after 12 weeks. We investigated the patients’ characteristics, disease history, concomitant medications, liver function, and liver stiffness. Results The efficacy rate of bezafibrate was 60% (15/25 patients). The efficacy rate in patients graded as Child–Pugh class A was significantly higher (75% [15/20]) than that in patients graded as class B (0% [0/5], P

Immunoglobulin G4 (IgG4)-related disease is a systemic inflammatory disorder that was first described in patients with autoimmune pancreatitis. Although IgG4-related disease is thought to involve the cardiovascular system, case reports describing coronary artery involvement are relatively rare. We describe a patient who was previously diagnosed with autoimmune pancreatitis and found to have coronary periarteritis and luminal narrowing. After the initiation of steroid treatment, the patient's coronary periarteritis and luminal stenosis were both ameliorated with an improvement in the serum IgG4 concentration. The present findings collectively suggest that IgG4-related immuno-inflammation may have a role in the development of coronary periarteritis and luminal atherosclerosis.

Background and aim An antireflux metal stent (ARMS) for nonresectable distal malignant biliary obstruction (MBO) may prevent recurrent biliary obstruction (RBO) as a result of duodenobiliary reflux and prolong time to RBO (TRBO). Superiority of ARMS over conventional covered self-expandable metal stents (SEMS) has not been fully examined. Methods We conducted a multicenter randomized controlled trial to examine whether TRBO of an ARMS with a funnel-shaped valve was longer than that of a covered SEMS in SEMS-naive patients. We enrolled 104 patients (52 patients per arm) at 11 hospitals in Japan. Secondary outcomes included causes of RBO, adverse events, and patient survival. Results TRBO did not differ significantly between the ARMS and covered SEMS groups (median, 251 vs 351 days, respectively; P = 0.11). RBO as a result of biliary sludge or food impaction was observed in 13% and 9.8% of patients who received an ARMS and covered SEMS, respectively (P = 0.83). ARMS was associated with a higher rate of stent migration compared with the covered SEMS (31% vs 12%, P = 0.038). Overall rates of adverse events were 20% and 18% in the ARMS and covered SEMS groups, respectively (P = 0.97). No significant between-group difference in patient survival was observed (P = 0.26). Conclusions The current ARMS was not associated with longer TRBO compared with the covered SEMS. Modifications including addition of an anti-migration system are required to use the current ARMS as first-line palliative treatment of distal MBO (UMIN-CTR clinical trial registration number: UMIN000014784).

To predict the duration of steroid maintenance therapy required to achieve good prognosis in patients with autoimmune pancreatitis.The study sample comprised 21 patients with autoimmune pancreatitis who met the following criteria: (1) they received steroid therapy (ST) for at least 3 years without clinical relapse; and (2) immunoglobulin (Ig) G1600 mg/dL was observed in the past year with a prednisolone maintenance dose ≤5 mg. All patients could be diagnosed with international consensus diagnostic criteria. Patients were prospectively followed up after tapering and cessation of steroids. Clinical relapse was defined as the need to resume ST. Serological relapse was defined as having an IgG level of1600 mg/dL.During the 43-month (range, 19 to 48 mo) follow-up period, clinical relapse occurred in 10 patients: pancreatic lesion in 4; coronary lesion in 2; submandibular lesion in 1; both pulmonary and renal lesions in 1; pulmonary, retroperitoneal, and submandibular lesions in 1; and bronchial asthma in 1. Serological relapse was observed in 12 patients. Although clinical and serological relapse occurred concomitantly in 3 patients, serological relapse preceded clinical relapse in 4 patients. Five patients experienced serological relapse alone, and no clinical or serological relapse occurred in 6 patients. According to Cox proportional hazard analysis, the duration of ST before tapering was a significant predictive parameter (hazard ratio, 0.969/month; 95% confidence interval, 0.940-0.998; P=0.038).ST cessation resulted in a high rate of clinical relapses, even in patients with long-term maintenance therapy. Therefore, it appears desirable to continue steroid maintenance therapy for a period3 years to prevent relapse.

BACKGROUND Sporadic autoimmune pancreatitis (AIP) cases showing remission without steroid treatment have been reported, however, the clinical course of these patients has not been clarified. This study sought to clarify the clinical course in AIP patients with hesitation for steroid treatment. METHODS We collected clinical data for AIP patients from high-volume centers in Japan. Data for AIP patients with and those without steroid treatment (steroid treatment vs. wait and see policy or W&S) were then compared. The primary point was the relapse-free survival rate (RFS) in patients with and those without steroid treatment, as determined using Kaplan-Meier curve. The secondary point was the identification of predictors of remission and risks of relapse in AIP patients without steroid treatment. RESULTS There were 510 AIP patients in the steroid treatment group and 97 patients in the W&S group. Overall, 55.7% (54/97) of type 1 AIP patients in the W&S group experienced transient remission without steroid treatment. The W&S group had a significantly higher patient age and significantly lower incidences of jaundice, diffuse pancreas swelling, proximal-type sclerosing cholangitis, and stent placement and a lower remission rate than the steroid treatment group (each P

Background Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease. Medical treatments must be devised to avoid or postpone liver transplantation in PSC patients. No clinical trial has prospectively explored the efficacy of bezafibrate in PSC patients. Methods We conducted a prospective study of 12-week bezafibrate treatment, with pre- and post-treatment observation periods, in PSC patients. Bezafibrate was prescribed at 200 mg b.i.d. The primary endpoint was defined as improvements in liver function test (LFT) data after bezafibrate treatment. Changes in LFT data during the study period were assessed every 6 weeks. Results Fifteen patients were enrolled as planned, and 11 completed the study protocol. Biliary enzyme levels improved in all patients after bezafibrate treatment for 12 weeks. Hepatic enzyme levels improved in only seven of the 11 patients, and the efficacy of bezafibrate in PSC patients was thus 64%. LFT data (alkaline phosphatase and alanine aminotransferase levels) were reduced after bezafibrate treatment (both P

An antireflux metal stent (ARMS) for distal malignant biliary obstruction has been reported to be useful, but the effectiveness of a flared-end structure to prevent migration on ARMS remains unclear. To evaluate the feasibility of a newly designed ARMS with both ends flared, 8 patients with covered metal stent occlusion due to sludge or food impaction were enrolled. ARMS were placed successfully after endoscopic removal of the occluded stents in all patients, and no procedure-related complication was observed. The median time to recurrent biliary obstruction was 71 days. ARMS occlusion occurred in 3 (38%) patients (sludge in 2 patients and hemobilia in 1). ARMS migration occurred in 1 (13%) patient. As a late complication, cholecystitis occurred in 1 (13%) patient. In conclusion, our newly designed ARMS with an antimigration system was technically feasible and safe, and a further investigation is warranted to evaluate the effectiveness of the current antimigration system.

Background It was recently reported that alkaline phosphatase (ALP) levels below 1.5 upper limit of normal (ULN) predicted better prognosis in primary sclerosing cholangitis (PSC). We evaluated whether ALP as well as other laboratory values were useful for the short-term prognosis of PSC in a Japanese cohort. Methods In 78 patients with PSC (41 males and 37 females, mean onset age 41.9 years), the relationship between nine parameters (albumin, bilirubin, international normalized ratio of prothrombin time [PT-INR], ALP, aspartate aminotransferase [AST], alanine aminotransferase [ALT], γ-glutamyl transpeptidase [γ-GTP], platelet, and calculated Model for End-Stage Liver Disease [MELD] score), and liver related clinical endpoints (death due to liver failure, variceal bleeding, liver transplantation, and biliary carcinoma) were retrospectively examined. Using receiver operating characteristic (ROC) analysis, we investigated which parameter was useful for predicting the short-term prognosis. Results Average follow-up period was 8.6 years. The endpoints were evaluated in 40 patients. Seven patients died of liver failure, three patients developed variceal bleeding, nine patients received liver transplantation from a living donor, 13 patients received certified brain-dead liver transplantation, and eight patients developed biliary carcinoma. The parameters with an area under the curve (AUC) of more than 0.8 were albumin, bilirubin, PT-INR, ALP, and MELD score. AUC for ALP was 0.85. The optimal cutoff value was 2.3 ULN. Despite the use or non-use of ursodeoxycholic acid, short-term prognosis of patients with an ALP level below 2.3 ULN was good. Conclusions We confirmed that keeping ALP low is associated with better short-term prognosis in a Japanese cohort. In addition, Alb, Bil, PT-INR, and MELD score were good predictors.

Wire-guided cannulation (WGC) was reported to decrease post-ERCP pancreatitis (PEP), but risk factors for PEP in WGC are not fully elucidated.To evaluate the incidence and risk factors of PEP in WGC.Single-center retrospective study.Academic center.A total of 800 consecutive patients with a native papilla.Biliary therapeutic ERCP by using WGC.The rate of PEP and its risk factors.Biliary cannulation was successful by using WGC alone in 70.5%, and the final cannulation rate was 96.1%. Unintentional guidewire insertion and contrast material injection into the pancreatic duct (PD) during cannulation occurred in 55.3% and 21.8%, respectively. The incidence of PEP was 9.5% (mild 5.6%, moderate 2.9%, severe 1.0%). Multivariate analysis revealed a common bile duct (CBD) diameter of 9 mm (odds ratio [OR] 2.03; P = .006) and unintentional guidewire insertion into the PD (OR 2.25; P = .014) as risk factors for PEP. PD opacification was not a risk factor for PEP (OR 1.15; P = .642), but the incremental increase of the PEP rate was seen in patients with CBDs 9 mm: 4.6% without any PD manipulation, 8.3% with contrast material alone, 16.9% with guidewire alone, and 22.1% with both contrast material and guidewire.Retrospective design in a single center.Unintentional PD manipulation was not uncommon in WGC. Guidewire insertion into the PD and a small CBD were risk factors for PEP in biliary therapeutic ERCP with the use of WGC.

Endoscopic nasobiliary drainage (ENBD) is often recommended in preoperative biliary drainage (PBD) for hilar malignant biliary obstruction (MBO), but endoscopic biliary stent (EBS) is also used in the clinical practice. We conducted this large-scale multicenter study to compare ENBD and EBS in this setting.A total of 374 cases undergoing PBD including 281 ENBD and 76 EBS for hilar MBO in 29 centers were retrospectively studied.Extrahepatic cholangiocarcinoma (ECC) accounted for 69.8% and Bismuth-Corlette classification was III or more in 58.8% of the study population. Endoscopic PBD was technically successful in 94.6%, and adverse event rate was 21.9%. The rate of post-endoscopic retrograde cholangiopancreatography pancreatitis was 16.0%, and non-endoscopic sphincterotomy was the only risk factor (odds ratio [OR] 2.51). Preoperative re-intervention was performed in 61.5%: planned re-interventions in 48.4% and unplanned re-interventions in 31.0%. Percutaneous transhepatic biliary drainage was placed in 6.4% at the time of surgery. The risk factors for unplanned procedures were ECC (OR 2.64) and total bilirubin ≥ 10 mg/dL (OR 2.18). In surgically resected cases, prognostic factors were ECC (hazard ratio [HR] 0.57), predraiange magnetic resonance cholangiopancreatography (HR 1.62) and unplanned re-interventions (HR 1.81). EBS was not associated with increased adverse events, unplanned re-interventions, or a poor prognosis.Our retrospective analysis did not demonstrate the advantage of ENBD over EBS as the initial PBD for resectable hilar MBO. Although the technical success rate of endoscopic PBD was high, its re-intervention rate was not negligible, and unplanned re-intervention was associated with a poor prognosis in resected hilar MBO.

Photo absorption properties of p-coumaric acid, the chromophore of photoactive yellow protein, in aqueous solution were investigated by means of reference interaction site model self-consistent field with spatial electron density distribution (RISM-SCF-SEDD) method. RISM-SCF-SEDD is a combination methodology of electronic structure theory and statistical mechanics for molecular liquids. Here, time-dependent density functional theory was coupled with RISM equation to study the electronic structure of p-coumaric acid in aqueous system. Excitation energies of the chromophore in its neutral, two monoanionic and dianionic forms were computed to elucidate the effect of the deprotonation and solvation on the spectroscopic properties. We found that solvation strongly affects the excitation character of the chromophore, especially for phenolate anion and dianion. The free energy difference among the four protonation states is also discussed. © 2017 Wiley Periodicals, Inc.

Primary sclerosing cholangitis (PSC) is a rare cholestatic disease. We previously reported the effects of bezafibrate on elevated hepatobiliary enzyme levels in patients with this disease both retrospectively and prospectively. In this study, we assessed factors predictive of bezafibrate efficacy.Twenty-five patients with PSC, who underwent bezafibrate therapy (400 mg per day) from November 2006 to June 2015, were evaluated. Treatment was judged as being effective if the levels of all of the hepatobiliary enzymes decreased after 12 weeks. We investigated the patients' characteristics, disease history, concomitant medications, liver function, and liver stiffness.The efficacy rate of bezafibrate was 60% (15/25 patients). The efficacy rate in patients graded as Child-Pugh class A was significantly higher (75% [15/20]) than that in patients graded as class B (0% [0/5], P 0.01). Non-responders had higher liver stiffness values (18.0 vs. 8.8 kPa, P = 0.19), and concomitantly used ursodeoxycholic acid more frequently (100% vs. 73%, P = 0.12) than responders.We could not elucidate the factors predictive for bezafibrate efficacy for the treatment of PSC. However, bezafibrate was more effective for patients with preserved liver function (Child-Pugh class A) when it was prescribed before progression of liver fibrosis and failure of ursodeoxycholic acid therapy.

The effect of maintenance steroid treatment (MST) in reducing the risk of relapse in patients with autoimmune pancreatitis (AIP) remains under debate. The aim of this study was to validate the effect of MST on AIP administered in accordance with the 2010 Japanese consensus guidelines.The clinical data of patients with (n = 510) from 22 high-volume centers in Japan were studied. The primary endpoints were the relapse rates (RRs) in patients administered MST versus those not administered MST. The secondary endpoints were the optimal dose and duration of MST in terms of steroid toxicity and the predictors of relapse.The RRs were 10.0% within 1 year, 25.8% within 3 years and 35.1% within 5 years. The RR in the steroid therapy group reached a plateau at 42.7% at 7 years. In terms of the optimal dosage, the overall RR in the MST 5 mg/day group was 26.1%, which was significantly lower than that in the group which had discontinued steroid therapy (45.2%; p = 0.023) or was receiving MST at 2.5 mg/day (43.4%, p = 0.001). The RRs in the group receiving MST at ≥5 mg/day versus the patient group receiving MST at5 mg/day were 10.6 vs. 10.3% within 1 year, 23.5 vs. 32.9% within 3 years and 32.2 vs. 41.3% within 5 years, respectively (log-rank, p = 0.028). The best cutoff value of the total steroid dose for serious steroid toxicity was 6405 mg, with a moderate accuracy of 0.717 determined using the area under the curve. Presence of diffuse pancreatic swelling [odds ratio OR) 1.745; p = 0.008) and MST at5 mg/day were identified as predictors of relapse (OR 0.483; p = 0.001).The RR could continue to increase for 7 years even under MST. Based on our analysis of the side effects of steroid therapy, MST at 5 mg/day for 2 (total 4625 mg) to 3 (total 6425 mg) years might be a rational and safe therapeutic strategy in terms of keeping the RR to30% while avoiding potential steroid toxicity.

Among the etiologies of pyogenic liver abscess (PLA), bacterial spread from the biliary tract or portal flow is the major cause, while the onset of PLA due to arterial bacterial transmission is rare. We herein report two cases of PLA thought to be caused by arterial transmission from dental disease. In both cases, there was benign biliary stricture as a result of alcoholic chronic pancreatitis, although normal oral flora was detected as the causative bacteria and oral hygiene was poor in both patients. We presumed that the origin of PLA was dental disease and successfully treated the patients with percutaneous drainage, antibiotics and dental procedures.

A super multi-view display provides three-dimensional images by emitting a lot of rays of different colors depending on the direction from each point on the display. It provides smooth motion parallax without special glasses, and it is expected that the observer is free from the visual fatigue caused by the accommodation-vergence conflict. However, a huge number of pixels are required on a display device because high-density rays are required for good quality images and each ray needs corresponding pixel. We proposed a new method to reduce the required number of pixels by limiting rays emitted to only around observer’s pupils. The display is based on the lenticular method. As stated above, the rays should be shot out to only around observer’s pupils. Therefore, the lenticular lens of which viewing zone angle is narrowed is used. But, due to the characteristics of the lenticular lens, the same image is seen repeatedly from different positions out of the viewing zone. It is called side lobe. Because of the side lobes, the rays for one eye enter the other eye. To suppress these side lobes, we proposed the lenticular lens is illuminated by the directional light. The direction of the directional light has to be changed to follow the observer’s eye. We implemented optical designs based on the technique as mentioned above, and we produced a prototype display. We experimented with consideration of change of viewing angle and viewing distance. We confirmed usefulness of the proposed display by these experiment result.

It was recently reported that alkaline phosphatase (ALP) levels below 1.5 upper limit of normal (ULN) predicted better prognosis in primary sclerosing cholangitis (PSC). We evaluated whether ALP as well as other laboratory values were useful for the short-term prognosis of PSC in a Japanese cohort.In 78 patients with PSC (41 males and 37 females, mean onset age 41.9 years), the relationship between nine parameters (albumin, bilirubin, international normalized ratio of prothrombin time [PT-INR], ALP, aspartate aminotransferase [AST], alanine aminotransferase [ALT], γ-glutamyl transpeptidase [γ-GTP], platelet, and calculated Model for End-Stage Liver Disease [MELD] score), and liver related clinical endpoints (death due to liver failure, variceal bleeding, liver transplantation, and biliary carcinoma) were retrospectively examined. Using receiver operating characteristic (ROC) analysis, we investigated which parameter was useful for predicting the short-term prognosis.Average follow-up period was 8.6 years. The endpoints were evaluated in 40 patients. Seven patients died of liver failure, three patients developed variceal bleeding, nine patients received liver transplantation from a living donor, 13 patients received certified brain-dead liver transplantation, and eight patients developed biliary carcinoma. The parameters with an area under the curve (AUC) of more than 0.8 were albumin, bilirubin, PT-INR, ALP, and MELD score. AUC for ALP was 0.85. The optimal cutoff value was 2.3 ULN. Despite the use or non-use of ursodeoxycholic acid, short-term prognosis of patients with an ALP level below 2.3 ULN was good.We confirmed that keeping ALP low is associated with better short-term prognosis in a Japanese cohort. In addition, Alb, Bil, PT-INR, and MELD score were good predictors.

OBJECTIVES Malignant ascites (MA) caused by peritoneal carcinomatosis is not uncommon in patients with pancreatic cancer. However, the clinical features and outcomes in these patients remain to be elucidated. METHODS Baseline characteristics and overall survival (OS) of consecutive patients with advanced pancreatic cancer who presented with MA were retrospectively evaluated. RESULTS Of 494 patients with advanced pancreatic cancer, 73 (15%) presented with MA. Patients with synchronous MA (n = 21), compared with those with metachronous MA (n = 52), had better performance status (P = 0.02), smaller amount of ascites (P < 0.01), and higher chance of receiving chemotherapy (57% vs 17%, P < 0.01), and resulted in longer OS (115 vs 42 days, P < 0.01). Overall survival was significantly longer in patients receiving chemotherapy than in those with best supportive care alone (124 vs 50 days, P < 0.01). In a multivariate analysis, chemotherapy was prognostic in addition to performance status, CRP, and small amount of MA; the hazard ratio of chemotherapy was 0.46, compared with best supportive care alone (P = 0.02). CONCLUSIONS Although the prognosis of pancreatic cancer patients with MA remains poor, selected patients may be candidate for chemotherapy, regardless of the timing of appearance of MA.

Endoscopic management of malignant biliary obstruction following hepaticojejunostomy can be challenging. With the advent of the short double-balloon endoscope (DBE), therapeutic biliary interventions are possible in surgically altered anatomy [1,2]. Additionally, a novel uncoveredmetal stent (UMS) has been developed with a 200-cm-long, 6-Fr delivery system (Zilver 635; Cook Medical, Winston-Salem, North Carolina, United States) to enable metal stent placement using a short DBE [3]. We present a successful case of multiple metal stenting using a short DBE and UMS for malignant biliary obstruction after hepaticojejunostomy. A 75-year-old man with extrahepatic bile duct cancer underwent pancreaticoduodenectomy with Roux-en-Y reconstruction. He developed cholangitis 11 months postoperatively as a result of liver metastasis in the medial left lobe segment. Endoscopic retrograde cholangiopancreatography (ERCP) was performed to place two plastic stents using a short DBE (EI-530B; Fujifilm Corp., Tokyo, Japan). However, rapid tumor growth resulted in recurrent episodes of cholangitis. Therefore, the decision was made to insert multiple metal stents via another ERCP using the short DBE. The plastic stents were removed, and the hepaticojejunostomy anastomosis was Fig.3 The second uncovered metal stent (UMS) was deployed through the mesh of the initial UMS. Fig.1 The first uncovered metal stent was deployed into the anterior branch of the right hepatic duct.

This paper explores to what extent line length can be shortened in a mixed-model assembly line by installing a single pull-off table. The number of resultant model sequences to which the table can be altered from the original model sequence compared with the number using random access buffers such as an automated storage and retrieval system is discussed. The line length realised by installing a pull-off table is also discussed based upon possible altered model sequences in order to provide guidelines on where to install a pull-off table. In addition, a procedure for installing a pull-off table is presented with a numerical example.