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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.

Background/aims To determine the nutritional markers important for assessing the degree of pancreatic insufficiency due to chronic pancreatitis in routine clinical practice. Methods A total of 137 patients with chronic pancreatitis were followed up for more than 1 year. They were divided into two groups: a pancreatic diabetes mellitus (DM) group, consisting of 47 patients undergoing medical treatment for DM of pancreatic origin, and a nonpancreatic DM group, consisting of 90 other patients (including 86 patients without DM). Serum albumin, prealbumin, total cholesterol, cholinesterase, magnesium, and hemoglobin were compared between the two groups. Results The total cholesterol was significantly lower in the pancreatic than the nonpancreatic DM group (164 mg/dL vs 183 mg/dL, respectively; p=0.0028). Cholinesterase was significantly lower in the former group (263 U/L vs 291 U/L, respectively; p=0.016). Among the 37 patients with nonalcoholic pancreatitis, there was no difference in the cholinesterase levels between the pancreatic and nonpancreatic (296 U/L vs 304 U/L, respectively; p=0.752) DM groups, although cholesterol levels remained lower in the former (165 mg/dL vs 187 mg/dL, respectively; p=0.052). Conclusions Cholinesterase levels are possibly affected by concomitant alcoholic liver injury. The total cholesterol level should be considered when assessing pancreatic insufficiency due to chronic pancreatitis.

Background and Aim To evaluate the efficacy and safety of secondary gastroduodenal stent placement after first stent dysfunction for malignant gastric outlet obstruction. Methods We conducted a retrospective analysis to investigate the efficacy and safety of secondary stent-in-stent gastroduodenal stent placement. Results Among 260 patients who had been treated with first gastroduodenal stent placement for malignant gastric outlet obstruction, 29 patients (11.2%) were treated with secondary gastroduodenal stent placement because of first stent dysfunction. Pancreatic cancer was the major primary cancer (55.2%). A WallFlex duodenal stent was the most frequently inserted stent both as a first stent (75.9%) and as a secondary stent (62.1%). There were 22 patients (75.9%) that received gastroduodenal stents at the bending site (supraduodenal angle or infraduodenal angle). Technical and clinical success rates were 100% and 86.2%, respectively. Median eating period was 3.0 months, and median survival time was 3.5 months. As for related complications, gastrointestinal perforation, insufficient stent expansion, tumor ingrowth, tumor overgrowth, and cholangitis were experienced in 13.8% (four cases), 6.9% (two cases), 6.9% (two cases), 3.4% (one case), and 3.4% (one case), respectively. Conclusion Secondary gastroduodenal stent placement might be effective for managing first stent dysfunction in malignant gastric outlet obstruction. However, gastrointestinal perforation was the major complication.

Background and Aim Covered metallic stents (CMSs) were developed to overcome tumor ingrowth in uncovered metallic stents (UMSs) for malignant biliary obstruction, but superiority of CMSs over UMSs is still controversial due to the high migration rate in CMS. Therefore, we conducted this retrospective analysis to clarify risk factors for stent migration, including mechanical properties of CMSs. Methods Patients with unresectable pancreatic cancer, receiving CMS for distal malignant biliary obstruction in five tertiary care centers, were retrospectively studied. Univariate and multivariate analyses to identify prognostic factors for early (

A subpopulation of patients with pancreas divisum experience symptomatic events such as recurrent acute pancreatitis and chronic pancreatitis. Minor papilla sphincterotomy has been reported as being an effective treatment. The aim of this study was to evaluate the safety and efficacy of endoscopic balloon dilation for the minor papilla.Between 2000 and 2012, 16 patients were retrospectively included in this study. After endoscopic balloon dilation for the minor papilla was received, a pancreatic stent or a nasal pancreatic drainage catheter was placed for 1 week. If a stricture or obstruction was evident, it was treated with balloon dilation followed by long-term stent placement (1 year). When an outflow of pancreatic juice was disturbed by a pancreatic stone, endoscopic stone extraction was performed.Balloon dilation and stent placement were achieved and were successful in all the cases (16/16; 100%). Clinical improvement was achieved in 7 (84.7%) of the 9 patients with recurrent acute pancreatitis and in 6 (85.7%) of the 7 patients with chronic pancreatitis. Early complications were observed in 1 (6.3%) patient. Pancreatitis or bleeding related to balloon dilation was not observed.Endoscopic balloon dilation for the minor papilla is feasible for the management of symptomatic pancreas divisum.

Background and Aim Tumor involvement to the orifice of cystic duct (OCD) is a risk factor for cholecystitis after self-expandable metallic stent (SEMS) placement, but its prevention is still difficult. We conducted this multicenter analysis to clarify a type of SEMS or a method to place SEMS which would decrease the incidence of cholecystitis after SEMS placement. Methods The incidence of cholecystitis was studied in consecutive patients receiving SEMS for distal malignant biliary obstruction in five tertiary care centers. Multiple logistic regression analysis was performed to evaluate risk factors for cholecystitis. Results A total of 376 patients who received SEMS placement for distal malignant biliary obstruction were analyzed. Tumor involvement to OCD was diagnosed in 25.3%. Overall incidence of cholecystitis was 6.9%. Cholecystitis was observed in 8.0% of 300 patients with covered SEMS, 16.8% of 95 patients with tumor involvement to OCD, 10.8% of 234 patients with SEMS of high axial force (AF), and 12.0% of 158 patients with SEMS length ≤ 60 mm. In the multivariate analysis, tumor involvement to OCD (odds ratio [OR] 5.40, P

Chronic inflammatory diseases are often associated with malignancy, and this phenomenon occurs even in the field of gastroenterology. For example, chronic pancreatitis has been reported to be highly associated with the occurrence of pancreatic cancer. However, the association between autoimmune pancreatitis (AIP) and pancreatic cancer is still an unsolved problem. As AIP is associated with immunoglobulin G4-related disease, which causes a variety of inflammatory and fibrotic lesions, the association between AIP and total malignancies is also a matter of interest. Here, we discuss the association between AIP and malignancy. As for the association between AIP and pancreatic cancer, there is no conclusive evidence, although several reports have suggested that the relative risk of pancreatic cancer is high in AIP. Concerning the association between AIP and total malignancies, there are two reports from Japan. Neither report supported the idea that chronic inflammation in AIP caused the increased risk of total malignancies. However, one report proposed the possibility that AIP might develop as a paraneoplastic syndrome in some patients because many cancers occurred within 1 year of AIP diagnosis, and thereby concluded that patients with AIP were at high risk of having various cancers. The paraneoplastic syndrome hypothesis should be tested in future studies.

E-cadherin is an important adhesion molecule whose loss is associated with progression and poor prognosis of liver cancer. However, it is unclear whether the loss of E-cadherin is a real culprit or a bystander in liver cancer progression. In addition, the precise role of E-cadherin in maintaining liver homeostasis is also still unknown, especially in vivo. Here we demonstrate that liver-specific E-cadherin knockout mice develop spontaneous periportal inflammation via an impaired intrahepatic biliary network, as well as periductal fibrosis, which resembles primary sclerosing cholangitis. Inducible gene knockout studies identified E-cadherin loss in biliary epithelial cells as a causal factor of cholangitis induction. Furthermore, a few of the E-cadherin knockout mice developed spontaneous liver cancer. When knockout of E-cadherin is combined with Ras activation or chemical carcinogen administration, E-cadherin knockout mice display markedly accelerated carcinogenesis and an invasive phenotype associated with epithelial-mesenchymal transition, up-regulation of stem cell markers, and elevated ERK activation. Also in human hepatocellular carcinoma, E-cadherin loss correlates with increased expression of mesenchymal and stem cell markers, and silencing of E-cadherin in hepatocellular carcinoma cell lines causes epithelial-mesenchymal transition and increased invasiveness, suggesting that E-cadherin loss can be a causal factor of these phenotypes. Thus, E-cadherin plays critical roles in maintaining homeostasis and suppressing carcinogenesis in the liver.

Objectives Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is diagnosed on the basis of pancreatic pain and hyperamylasemia. However, because the diagnosis of abdominal pain is not objective, there may be some cases of painless pancreatitis among patients with post-ERCP hyperamylasemia (PEH). We reviewed the computed tomography (CT) findings of PEH cases to determine the incidence of painless pancreatitis. Methods Between July, 2005 and December, 2011, CT was performed in 91 patients with hyperamylasemia 18 h after ERCP. We reviewed the CT findings and graded the severity of pancreatitis according to the Balthazar grading system. Grades C, D, and E were defined as pancreatitis. Results Thirty-four patients (37%) had pancreatitis according to the CT findings. There was a significant difference in the serum amylase levels between the positive- and negative-CT finding groups (1306 ± 833 vs. 786 ± 315 IU/L, respectively; p = 0.0012). Receiver operating characteristic curve analysis showed that the amylase cut-off value for discriminating between the 2 groups was 795 IU/L (6.36 times the upper normal limit). Conclusions Thirty-seven percent of PEH patients had painless pancreatitis. CT is useful to determine pancreatitis in patients taking analgesics, steroids, or anti-immunological drugs and those with diabetes mellitus and 18-h serum amylase levels of >6 times the normal upper limit.

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.

Background/Aims: Stent migration occurs frequently, but the prevention of complications resulting from covered self- expandable metal stents (C-SEMSs) remains unresolved. We prospectively assessed a newly developed C-SEMS, a modi- fied covered Zeo stent (m-CZS), in terms of its antimigration effect. Methods:�Between February 2010 and January 2011, an m-CZS was inserted into 42 patients (31 initial drainage cases and 11 reintervention cases) at a tertiary referral center and three affiliated hospitals. The laser-cut stent was flared for 1.5 cm at both ends, with a 1 cm raised bank located 1 cm in from each flared end. The main outcome of this study was the rate of stent migration, and second- ary outcomes were the rate of recurrent biliary obstruction (RBO), the time to RBO, the frequencies of complications, and overall survival. Results:�Of the 31 patients with initial drainage, stent migration occurred in four (12.9%, 95% con- fidence interval, 5.1% to 29.0%), with a mean time of 131 days. RBO occurred in 18 (58%), with a median time to RBO of 107 days. Following previous C-SEMS migration, seven of 10 patients (70%) did not experience m-CZS migration until death. Conclusions:�m-CZSs with antimigration properties ef- fectively, although not completely, prevented stent migration after stent insertion. (GutLiver�2013;7:725-730)

We increasingly encounter pancreatic cystic neoplasms (PCN) in clinical practice and the differential diagnoses vary widely from benign to malignant. There is no 'one and only' diagnostic procedure for PCN. Multiple modalities including computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography and endoscopic ultrasound (EUS) are widely used, but EUS has the advantage of anatomical proximity to the pancreas and upper gastrointestinal tract. In addition, EUS-guided fine-needle aspiration (EUS-FNA) provides both cytological evaluation and cyst fluid analysis. Although the role of EUS-FNA for PCN is established, the sensitivity of cytology is low and cyst fluid analysis is only useful for differentiation between mucinous and non-mucinous cysts. Recently, novel through-the-needle imaging under EUS-FNA, such as confocal laserendomicroscopy, is expected to attribute to a better diagnostic yield. Moreover, feasibility of cyst ablation has been reported and the role of EUS has expanded from diagnosis to treatment. However, clinical impact of cyst ablation in terms of safety, efficacy and cost-effectiveness should be validated further. In summary, EUS and EUS-guided intervention does and will play a central role in the management of PCN from surveillance to treatment, but many clinical questions remain unanswered, which warrants well-designed prospective clinical trials.

Background and Aim IgG4-related sclerosing cholangitis (IgG4-SC) must be precisely distinguished from primary sclerosing cholangitis and cholangiocarcinoma (CC) because the treatments are completely different. However, the pathological diagnosis of IgG4-SC is difficult. Therefore, highly specific non-invasive criteria such as serum IgG4 should be established. This study established a cut-off for serum IgG4 to differentiate IgG4-SC from respective controls using serum IgG4 levels measured in Japanese centers. Methods A total of 344 IgG4-SC patients were enrolled in this study. As controls, 245, 110, and 149 patients with pancreatic cancer, primary sclerosing cholangitis, and CC, respectively, were enrolled. IgG4-SC patients were classified into three groups: type 1 (stenosis only in the lower part of the common bile duct), type 2 (stenosis diffusely distributed throughout the intrahepatic and extrahepatic bile ducts), and types 3 and 4 (stenosis in the hilar hepatic region) with 246, 56, and 42 patients, respectively. Serum IgG4 levels were compared, and the cut-offs were established. Results The cut-off obtained from receiver operator characteristic curves showed similar sensitivity and specificity to that of 135 mg/dL when all IgG4-SC and controls were compared. However, a new cut-off value was established when subgroups of IgG4-SC and controls were compared. A cut-off of 182 mg/dL can increase the specificity to 96.6% (4.7% increase) for distinguishing types 3 and 4 IgG4-SC from CC. A cut-off of 207 mg/dL might be useful for completely distinguishing types 3 and 4 IgG4-SC from all CC. Conclusions Serum IgG4 is useful for the differential diagnosis of IgG4-SC and controls.

Yamaguchi et al. have recently identified positions of hydrogen and deuterium atoms in photoactive yellow protein (PYP) using high-resolution neutron scattering. They reported that the hydrogen bond between the PYP chromophore and Glu46 was not a short ionic hydrogen bond (SIHB) but a low barrier hydrogen bond (LBHB). Furthermore, it was suggested that Arg52 close to the chromophore was deprotonated. In the present study, we investigate the electronic structure of the chromophore in PYP under the condition of protonated or deprotonated Arg52. By analyzing the potential energy curve along the proton migration between Glu46 and the chromophore, we find that a LBHB can be seen only when Arg52 is deprotonated.

Sclerogenic biliary changes in hepatic amyloidosis are seldom observed. Here, we report two recent cases initially suspected as primary sclerosing cholangitis (PSC), which were later diagnosed as hepatic amyloidosis (AL type). Case 1: On the basis of magnetic resonance cholangiopancreatography (MRCP) findings, PSC was suspected in a 41-year-old woman with jaundice. Computed tomography (CT) showed nodular pulmonary lesions and swollen cervical, mediastinal and para-aortic lymph nodes, the cause of which was unknown despite detailed examinations. Because of rapid deterioration in the patient's liver function, living donor liver transplantation was performed. She was then diagnosed with hepatic amyloidosis, but died of heart failure due to cardiac amyloidosis 74 days after surgery. Case 2: On the basis of MRCP findings, PSC was suspected in a 49-year-old woman with jaundice. CT showed multiple cystic pulmonary lesions, and hypogammaglobulinemia was also observed (immunoglobulin G, 481 mg/dL). After a biliary plastic stent was placed, liver and lung biopsy confirmed the presence of amyloid deposition. These two cases indicate that it is important to consider hepatic amyloidosis as a differential diagnosis of PSC. The presence of atypical extrahepatic lesions may be useful clues for confirming the diagnosis.

Background Self-expandable metallic stent (SEMS) placement is widely carried out for distal malignant biliary obstruction, and survival analysis is used to evaluate the cumulative incidences of SEMS dysfunction (e.g. the Kaplan–Meier [KM] method and the log–rank test). However, these statistical methods might be inappropriate in the presence of ‘competing risks’ (here, death without SEMS dysfunction), which affects the probability of experiencing the event of interest (SEMS dysfunction); that is, SEMS dysfunction can no longer be observed after death. A competing risk analysis has rarely been done in studies on SEMS. Patients and Methods We introduced the concept of a competing risk analysis and illustrated its impact on the evaluation of SEMS outcomes using hypothetical and actual data. Our illustrative study included 476 consecutive patients who underwent SEMS placement for unresectable distal malignant biliary obstruction. Results A significant difference between cumulative incidences of SEMS dysfunction in male and female patients via theKM method (P = 0.044 by the log–rank test) disappeared after applying a competing risk analysis (P = 0.115 by Gray's test). In contrast, although cumulative incidences of SEMS dysfunction via the KM method were similar with and without chemotherapy (P = 0.647 by the log–rank test), cumulative incidence of SEMS dysfunction in the non-chemotherapy group was shown to be significantly lower (P = 0.031 by Gray's test) in a competing risk analysis. Conclusion Death as a competing risk event needs to be appropriately considered in estimating a cumulative incidence of SEMS dysfunction, otherwise analytical results may be biased.

Diabetes mellitus (DM) is recognized as a risk factor for pancreatic cancer (PaC) and expected to be a clue for early diagnosis. However, it is still obscure whether a diagnostic strategy using DM as a clue can improve the prognosis or not.We retrospectively reviewed 540 patients with PaC, and investigated the prognosis with regard to the reasons for diagnosis. We compared patients diagnosed by imaging studies performed when DM was newly diagnosed or deteriorated, and patients diagnosed by symptoms.The prevalence of DM in PaC patients was 45% (256/540) and did not differ between disease stages. More than half of DM in PaC patients (150/256) were new-onset (2 years in duration). One hundred sixty one patients (30%) were asymptomatic at PaC diagnosis. There were 38 patients diagnosed in association with DM (by new-onset DM, 16; by aggravation of long-standing DM, 22). Asymptomatic patients had smaller primary tumor and were diagnosed at an earlier stage. The prognosis of PaC patients complicated with DM did not differ from that of patients without DM; however, patients had better prognosis if they were diagnosed in association with DM alone (median survival time, 20.2 months), compared with patients diagnosed by symptoms (10.2 months, P 0.01).Our analysis revealed that patients diagnosed in association with DM had better survival than symptomatic patients. Given the high prevalence of DM in PaC patients, DM can be a useful diagnostic clue for screening and lead to improvement of prognosis in PaC patients.