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The appropriate method of preoperative endoscopic biliary drainage (EBD) for cholangiocarcinoma with hilar biliary obstruction remains controversial. The inside-stent technique is a method of placing plastic stents entirely inside the bile duct. Several studies of patients with unresectable stage have reported longer stent patency compared with conventional endoscopic biliary stenting (EBS). Inside-stent techniques have been introduced as a bridge-to-surgery option and as an alternative to conventional EBS.We aimed to evaluate the clinical outcomes of inside stent use and conventional EBS.During this retrospective multicenter study, we reviewed consecutive patients with cholangiocarcinoma who underwent radical surgery after conventional EBS or inside-stent insertion. Adverse event (AE) rates after EBD and post-surgical AEs were compared. A multivariable analysis was performed to identify factors affecting cholangitis after EBD.Conventional EBS and inside-stent procedures were performed for 56 and 73 patients, respectively. Patient backgrounds were similar between groups, except for percutaneous transhepatic portal vein embolization. The waiting time before surgery was similar between groups (28.5 days vs. 30 days). There were no significant differences in the cholangitis rate (21.4% vs. 26.0%; P = 0.68) and all AEs (25.0% vs. 30.1%; P = 0.56) between groups. The post-surgical AE rate was similar between the groups. The multivariable analysis found that preprocedural cholangitis was a risk factor for cholangitis after EBD (odds ratio: 5.67; 95% confidence interval: 1.61-19.9).The outcomes of inside-stent techniques and conventional EBS for the management of preoperative EBD are comparable for patients with cholangiocarcinoma.

Gastrinoma may cause refractory esophageal stricture due to gastro-esophageal reflux disease (GERD), but imaging technologies have limited power in its diagnosis. A 74-year-old female with a history of peptic ulcers suffered from repeated epigastralgia, and she visited a local hospital. An esophago-gastro-duodenoscopy (EGD) demonstrated severe reflux esophagitis and multiple peptic ulcers. Blood examination revealed a high value of fasting serum gastrin. Multi-detector computed tomography showed a hypervascular and tiny nodule in duodenal bulb, although other imaging technologies did not. Short-term medication with a proton pump inhibitor or potassium-competitive acid blocker was intermittently provided, but dysphagia was repeatedly worsened, and she was referred to our division. Serum hypergastrinemia was retained, and EGD reexamination depicted esophageal stricture, treated by multiple sessions of endoscopic balloon dilatation. Primary tumor was not identified by the morphological imaging technologies, but a selective arterial secretagogue injection test suggested its existence in the duodenum or pancreatic head. Pancreaticoduodenectomy was performed, and histological study identified 2 mm-sized microgastrinoma buried in Brunner`s glands on the posterior wall of the duodenum bulb. We reported a case with difficulty in diagnosis of the smallest sporadic gastrinoma of the duodenum, which might cause refractory GERD-associated stricture.

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

Proper assessment of disease activity and prediction of relapse are crucial for the management of autoimmune pancreatitis (AIP). The M-ANNHEIM-AiP-Activity-Score (MAAS) has been proposed to determine disease activity and predict relapse in German and Swedish patients with AIP. MAAS is calculated using six categories: pain report, pain control, exocrine insufficiency, endocrine insufficiency, imaging, and complications. This study aimed to clarify the usefulness of MAAS to predict relapse in Japanese patients with type 1 AIP.We retrospectively analyzed 117 patients with type 1 AIP undergoing initial and maintenance steroid treatments at our institute between April 2006 and March 2021. AIP was diagnosed according to the Japanese Diagnostic Criteria for AIP 2018. We examined the association of MAAS with relapse during and after maintenance treatment.MAAS (median, 8 points) at the start of the initial treatment was reduced after treatment (median, 4 points; P 0.001). A MAAS ≥11 points at the start of the initial treatment was associated with relapse. The initial treatment-induced reduction of MAAS60% was more frequent in patients with relapse (75.0%) than in patients without relapse (37.6%; P = 0.007). MAAS at the start of maintenance treatment was higher for patients with relapse (median, 5 points) than that for patients without relapse (median, 4 points; P = 0.007). MAAS ≥4 points at the start of maintenance treatment was associated with subsequent relapse.MAAS is useful for predicting relapse in patients with type 1 AIP undergoing maintenance therapy.

A 64-year-old man was admitted to our hospital to undergo examination of a pancreatic tumor accompanied by sudden epigastric pain. The tumor had a well-defined oval shape that was mostly less enhanced, with the exception of part of the tumor on the pancreatic head side, on contrast enhanced (CE)-CT. However, CE-CT performed one-month later revealed that the viable part of the tumor grew toward the pancreatic tail with the reduction of necrotic tissue. We performed distal pancreatectomy and the tumor was diagnosed as acinar cell carcinoma (ACC). One important characteristic of ACC is that it may develop morphological changes within a short period of time.

Loss of function in the BRCA2 gene exacerbates ovarian, breast, and pancreatic ductal cancer risk. Despite being implicated in the pancreatic ductal epithelium carcinogenesis, the involvement of a germline BRCA2 mutation in acinar and endocrine cells is less reported. A 45-year-old woman with a history of breast cancer was referred to our hospital for a detailed examination of epigastric pain. Her father had pancreatic cancer, and her paternal aunt had a history of breast cancer. Contrast-enhanced computed tomography revealed a round tumor with a contrast effect in the pancreatic head. The patient underwent pancreaticoduodenectomy, and postoperative pathology and genetic testing revealed amphicrine-type mixed acinar-neuroendocrine carcinoma with a germline BRCA2 mutation. Recent studies have reported the BRCA2 mutation in genome sequencing of pancreatic acinar cell carcinoma and neuroendocrine tumor; perhaps, genetic testing for the BRCA2 mutation is feasible for patients with mixed neuroendocrine-non-neuroendocrine neoplasm.

Background To provide updates on clinical practice of acute pancreatitis (AP) in Japan, we conducted a nationwide epidemiological survey. Methods This study consisted of a two-staged survey; the number of AP patients was estimated by the first-stage survey and their clinical features were examined by the second-stage survey. We surveyed AP patients who had visited hospitals in 2016. Results The estimated number of AP patients in 2016 was 78,450, with an overall incidence of 61.8 per 100,000 persons. We obtained detailed clinical information of 2994 AP patients, including 706 (23.6%) severe cases classified according to the Japanese severity criteria. The male-to-female sex ratio was 2.0, and the mean age at onset was 59.9 years in males and 66.5 years in females. Alcohol was the most common etiology (42.8%) in males and gallstones in females (37.7%). The AP-associated mortality was 6.1% in severe AP cases, which was decreased by 40% compared to the 2011 survey. Antibiotics were administered to most cases, with carbapenem being frequently used. Enteral nutrition was given in 31.8% of severe cases, but majority cases received after 48 h. Among the 107 patients who received intervention for walled-off necrosis, five patients received surgery-first approach, 66 received endoscopic ultrasound-guided transluminal drainage, and 19 underwent step-up approach. Conclusions We clarified the current status of AP in Japan including the significant reduction of mortality in severe cases, shift to endoscopic approaches for walled-off necrosis, and poor compliance of the recommendations in the guidelines including management of enteral nutrition and antibiotic administration.

A 58-year-old man was referred for obstructive jaundice. Imaging modalities revealed the presence of multiple pancreatic tumors and the stenosis of the middle common bile duct due to a hypoenhanced localized tumor. The multiple pancreatic tumors were histopathologically diagnosed as autoimmune pancreatitis by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). To differentiate between IgG4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma, we diagnosed the biliary tumor as IgG4-SC by EUS-FNA because of insufficient pathological materials obtained in a transpapillary manner. We herein report a case of IgG4-SC diagnosed by EUS-FNA.

Pancreatic ductal adenocarcinoma (PDAC), which accounts for majority of pancreatic cancers, is one of the most lethal human malignancies. Most patients are diagnosed at an advanced stage after symptom development. Early diagnosis of PDAC in asymptomatic subjects is important to improve prognosis. Diabetes mellitus (DM) is a risk factor for PDAC, and DM, especially new-onset DM, has attracted attentions as a diagnostic clue to PDAC. However, the impact of DM as a diagnostic opportunity on the prognosis of PDAC is unclear. We here retrospectively reviewed 489 PDAC patients and compared the clinical characteristics and prognosis according to the opportunities for PDAC diagnosis. PDAC was diagnosed upon presentation of symptoms, such as pain and jaundice, in 318 cases including 151 DM patients, upon new-onset or exacerbation of long-standing DM in 53 asymptomatic patients, and upon incidental detection by medical check-up or follow-up/work-up of other diseases in 118 asymptomatic patients. Asymptomatic patients including those with DM had smaller tumors, earlier disease stage, and higher resectability rates than symptomatic patients. Asymptomatic patients diagnosed in association with DM had better prognosis (median survival time, 771 days) than those diagnosed due to symptoms (343 days, P < 0.001), and similar to those diagnosed by incidental detection (869 days). The survival advantage was not evident in symptomatic patients with DM-associated signs. In conclusion, patients diagnosed in association with DM at asymptomatic stages had better prognosis than those diagnosed with symptoms. DM-associated signs might provide a clue to the early diagnosis of PDAC among asymptomatic subjects.

BackgroundContinuous regional arterial infusion (CRAI) of protease inhibitor nafamostat mesilate (NM) is used in the context of predicted severe acute pancreatitis (SAP) to prevent the development of pancreatic necrosis. Although this therapy is well known in Japan, its efficacy and safety remain unclear.MethodsThis investigator-initiated and -driven, multicenter, open-label, randomized, controlled trial (UMIN000020868) enrolled 39 patients with predicted SAP and low enhancement of the pancreatic parenchyma on computed tomography (CT). Twenty patients were assigned to the CRAI group, while 19 served as controls and were administered NM at the same dose intravenously (IV group). The primary endpoint was the development of pancreatic necrosis as determined by CT on Day 14, judged by blinded central review.ResultsThere was no difference between the CRAI and IV groups regarding the percentages of participants who developed pancreatic necrosis (more than 1/3 of the pancreas: 25.0%, range 8.7–49.1% vs. 15.8%, range 3.4–39.6%, respectively,P = 0.694; more than 2/3 of the pancreas: 20%, range 5.7–43.7% vs. 5.3%, range 0.1–26.0%, respectively,P = 0.341). The early analgesic effect was evaluated based on 24-h cumulative fentanyl consumption and additional administration by intravenous patient-controlled analgesia. The results showed that the CRAI group used significantly less analgesic. There were two adverse events related to CRAI, namely bleeding and splenic infarction.ConclusionsCRAI with NM did not inhibit the development of pancreatic necrosis although early analgesic effect of CRAI was superior to that of IV. Less-invasive IV therapy can be considered a viable alternative to CRAI therapy.

In patients with malignant perihilar biliary strictures, preoperative biliary drainage (PBD) of the hepatic lobe to be resected may decrease the liver volume of the future liver remnant (FLR) after percutaneous transhepatic portal vein embolization (PVE). However, evidence of its application is insufficient. This study aimed to clarify the effects of PBD on liver hypertrophy after PVE. Between January 2008 and December 2017, 169 patients with malignant perihilar biliary strictures underwent major hepatectomy or palliative surgery at our hospital. Of these, 76 patients who underwent PVE were categorized into two groups: group A (n = 29) who received unilateral PBD of the FLR and group B (n = 47) who received bilateral PBD, including that of the hepatic lobe to be resected. FLR ratios after PVE and liver hypertrophy ratios were retrospectively compared in both groups. Group B exhibited significantly severe biliary stenosis (p = 0.0038) and high serum bilirubin before biliary drainage (p = 0.0037). After PVE, the total liver volumes were 1287 ± 260 ml and 1340 ± 257 ml (p = 0.39), respectively. FLR volumes were 555 ± 135 and 577 ± 113 ml (p = 0.45), respectively. FLR ratios were 43.4 ± 8.2% and 43.4 ± 6.4%, respectively (p = 0.98). Liver hypertrophy ratios were 124.2 ± 17.7% and 129.2 ± 20.9%, respectively (p = 0.28). In addition, an examination which excluded patients with Bismuth type I obtained similar result. PBD of the hepatic lobe to be resected did not decrease the FLR ratios and hypertrophy ratios. Thus, in patients with poor biliary drainage, additional PBD of the target lobe is acceptable.

A 71-year-old man underwent surgery for a pancreatic neuroendocrine tumor. Follow-up imaging showed swelling of the remnant pancreas, and he was histologically diagnosed with autoimmune pancreatitis based on endoscopic ultrasonography-guided fine-needle aspiration specimens. After two years, a tumor appeared on the liver surface. Although we planned to perform laparoscopic partial hepatectomy, the intraoperative findings showed that the tumor was located in the diaphragm. Partial resection of the diaphragm was performed, and the final diagnosis was an immunoglobulin G4-related inflammatory pseudotumor in the diaphragm. To our knowledge, this is the first reported case of an immunoglobulin G4-related diaphragmatic inflammatory pseudotumor.

A 71-year-old man underwent surgery for a pancreatic neuroendocrine tumor. Follow-up imaging showed swelling of the remnant pancreas, and he was histologically diagnosed with autoimmune pancreatitis based on endoscopic ultrasonography-guided fine-needle aspiration specimens. After two years, a tumor appeared on the liver surface. Although we planned to perform laparoscopic partial hepatectomy, the intraoperative findings showed that the tumor was located in the diaphragm. Partial resection of the diaphragm was performed, and the final diagnosis was an immunoglobulin G4-related inflammatory pseudotumor in the diaphragm. To our knowledge, this is the first reported case of an immunoglobulin G4-related diaphragmatic inflammatory pseudotumor.

Pancreatic cancer is one of the most dangerous solid tumors, but its early diagnosis is difficult. The abnormality of the main pancreatic duct (MPD), such as a single localized stricture and upstream dilatation, might be useful in the early detection of pancreatic cancer. However, these findings are often observed in benign inflammatory cases. This study aimed to clarify whether early pancreatic cancer presenting MPD abnormalities has characteristic features different from those of benign cases. This is a single-center, retrospective study. We analyzed 20 patients who underwent pancreatectomy presenting with a single, localized MPD stricture without identifiable masses on imaging: 10 patients with pancreatic ductal adenocarcinoma (cancer group; 6 with stage 0 and 4 with stage I) and 10 patients with benign strictures (benign group; 8 with inflammation and 2 with low-grade pancreatic intraepithelial neoplasms). Pancreatectomy was performed in these benign cases because high-grade intraepithelial neoplasm was suspected. Although the proportion of patients with diabetes mellitus tended to be higher in the cancer group (6/10) than that in the benign group (1/10) (P = 0.058), other clinical characteristics were not different between the groups. Preoperative cytological malignancies were detected in four patients in the cancer group (4/10) but not in the benign group (P = 0.09). Focal parenchymal atrophy and fat replacement were more frequently detected on computed tomography in the cancer group (7/10) than in the benign group (1/10) (P = 0.02). In conclusion, focal parenchymal atrophy and fat replacement may provide clues for the early diagnosis of pancreatic cancer.

A 79-year-old woman was referred for pancreatic tail cancer with multiple liver metastases. The pancreatic tail tumor was diagnosed as acinar cell carcinoma (ACC) histologically by endoscopic ultrasound-guided fine-needle aspiration. Because of multiple liver metastases, S-1 chemotherapy was administered, resulting in a partial response to chemotherapy one year later. After approximately three years, liver atrophy and esophageal varices developed. We suspected S-1 as the cause of the liver cirrhosis. S-1 cessation minimized ascites and improved the esophageal varices. Although S-1 can potentially treat ACC, we should be watchful for liver cirrhosis caused by its long-term administration.

Pancreaticojejunostomy stricture (PJS) is a late complication of pancreaticoduodenectomy. The endoscopic treatment of PJS is very challenging due to the difficulty of locating the small anastomotic site and passing the stricture using a guidewire. We herein report two cases of severe PJS. These patients could not be treated using only double-balloon endoscopy or endoscopic ultrasound-guided puncture of the main pancreatic duct because of severe stenosis at the anastomotic site. However, we could treat them by the rendezvous technique using the rigid part of the guidewire to penetrate PJS. This method was useful and safe for treating severe PJS.

A 32-year-old woman was referred due to abdominal pain and elevated liver enzymes. Computed tomography and magnetic resonance imaging showed ectopic opening of the common bile duct (CBD) into the duodenal bulb. Esophagogastroduodenoscopy showed a hemispheric bulge in the duodenal bulb. Endoscopic retrograde cholangiopancreatography (ERCP) revealed the bulge to be cystic dilatation of the CBD. ERCP also showed no communication between the ventral and dorsal pancreatic ducts. We diagnosed the patient with ectopic opening of the CBD accompanied by choledochocele and pancreas divisum. Endoscopic incision was performed for the treatment of the choledochocele. The patient's symptoms and elevated liver enzymes improved after treatment.

The prognosis of pancreatic cancer is dismal due to the frequent metastasis and invasion to surrounding organs. Numerous molecules are involved in the malignant behavior of pancreatic cancer cells, but the entire process remains unclear. Several reports have suggested that CUB-domain containing protein-1 (CDCP1) is highly expressed in pancreatic cancer, but its impact on the invasive growth and the upstream regulator remain elusive. To clarify the role of CDCP1 in pancreatic cancer, we here examined the effects of CDCP1 knockdown on the cell behaviors of pancreatic cancer cells. Knockdown of CDCP1 expression in Panc-1 resulted in reduced cellular migration accompanied by the increased expression of E-cadherin and decreased expression of N-cadherin. Knockdown of CDCP1 attenuated the spheroid formation and resistance against gemcitabine, which are some of the cancer stem cell-related phenotypes. Bone morphogenetic protein 4 (BMP4) was found to induce CDCP1 expression via the extracellular signal regulated kinase pathway, suggesting that CDCP1 has a substantial role in the BMP4-induced epithelial-mesenchymal transition. These results indicate that CDCP1 represses the epithelial phenotype of pancreatic cancer cells.

Nickel nanoparticles (NiNPs) were successfully synthesized in situ on a microstructured paper matrix composed of inorganic fibers as the main framework and zinc oxide (ZnO) whiskers as a preferential support for NiNPs. The paper-like inorganic fiber/ZnO whisker composites were prepared using a high-speed and low-cost papermaking technique, and then simply immersed in an aqueous solution of Ni(NO3)2. After reduction in hydrogen flow, NiNPs with a fine size about 20 nm in diameter were selectively formed on the ZnO whiskers in the paper composites. As-prepared NiNPs@ZnO paper is much like an ordinary paper product, being flexible, lightweight, and easy to handle. The NiNPs@ZnO paper composites exhibited excellent catalytic performance in the steam reforming of propane, and produced hydrogen more efficiently than commercial pellet-type nickel catalysts. These results are possibly attributed both to highly active NiNPs synthesized in situ and to the uniform flow of reactants inside a microporous paper structure.

In situ synthesis of nickel/magnesium oxides (Ni/MgO) on a microstructured inorganic paper support was investigated to develop high-performance, easily handled, paper-like catalysts, using two different methods: sequential impregnation and co-impregnation approaches. Porous paper supports were prepared beforehand using a conventional papermaking technique, and then simply impregnated with Mg(NO 3 ) 2 and Ni(NO 3 ) 2 solutions, either stepwise or at the same time. After reduction in a hydrogen flow, Ni/MgO catalysts were formed in the paper composites. The as-prepared Ni/MgO paper is much like an ordinary paper product, being flexible, lightweight, and easy to handle. The Ni/MgO paper composites, especially the co-impregnated paper, exhibited excellent catalytic performances in the steam reforming of methane, and produced hydrogen much more efficiently than did commercial Ni-based catalysts in powdered and pellet forms. The Ni/MgO paper composites also showed good durability for 24-h continuous reaction, and maintained their initial efficiency for methane steam reforming. These results were attributed to the favorable supply of gaseous reactants to the active Ni/MgO catalysts, which were well distributed inside a microporous paper structure.

There is accumulating evidence that pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, promote the progression of pancreatic cancer. The interactions between PSCs and pancreatic cancer have attracted substantial attention as a novel therapeutic target for the treatment of pancreatic cancer. We examined here the effects of olmesartan, an angiotensin II type I receptor blocker, on pancreatic cancer-associated fibrosis using a subcutaneous tumor model developed by co-injection of pancreatic cancer cells with PSCs in nude mice. Co-injection of pancreatic cancer cells AsPC-1 with PSCs increased the size of tumors compared with AsPC-1 cells alone. Olmesartan administrated at 10 mg/kg in drinking water inhibited the growth of subcutaneous tumors derived from the co-injection, but not those derived from mono-injection. This effect was accompanied by decreased expression of α-smooth muscle actin (a marker of activated PSCs) and collagen deposition. The inhibitory effect of olmesartan was also observed even if it was administrated after significant development of subcutaneous tumors. In addition, olmesartan decreased cell growth and type I collagen production in PSCs in vitro. These results suggest that olmesartan inhibited the growth of tumors by targeting stellate cell activities, and that olmesartan might be useful as an anti-fibrosis therapy in pancreatic cancer.

Invasive ductal adenocarcinoma (IDA) of the pancreas manifests poor prognosis due to the early invasion and distant metastasis. In contrast, intraductal papillary mucinous adenoma or carcinoma (IPMA or IPMC) reveals better clinical outcomes. Various molecular mechanisms contribute to these differences but entire picture is still unclear. Recent researches emphasized the important role of miRNA in biological processes including cancer invasion and metastasis. We previously described that miR-126 is down-regulated in IDA compared with IPMA or IPMC, and miR-126 regulates the expression of invasion related molecule disintegrin and metalloproteinase domain-containing protein 9 (ADAM9). Assessing the difference of miRNA expression profiles of IDA, IPMA, and IPMC, we newly identified miR-197 as an up-regulated miRNA specifically in IDA. Expression of miR-197 in pancreatic cancer cells resulted in the induction of epithelial-mesenchymal transition (EMT) along with the down-regulation of p120 catenin which is a putative target of miR-197. Direct interaction between miR-197 and p120 catenin mRNA sequence was confirmed by 3'UTR assay, and knockdown of p120 catenin recapitulated EMT induction in pancreatic cancer cells. In situ hybridization of miR-197 and immunohistochemistry of p120 catenin showed mutually exclusive patterns suggesting pivotal role of miR-197 in the regulation of p120 catenin. This miR-197/p120 catenin axis could be a novel therapeutic target.

Background and study aim: Self-expandable metallic stents (SEMSs) are used for palliation in patients with malignant perihilar biliary strictures. However, recurrent biliary obstruction occasionally causes cholangitis and jaundice. This study aimed to identify risk factors for recurrent biliary obstruction in such patients. Methods: Data from consecutive patients with malignant perihilar biliary strictures treated with endoscopic placement of SEMSs between 2007 and 2014 in Tohoku University Hospital were retrospectively reviewed. Risk factors for recurrent biliary obstruction were calculated using the Cox proportional hazards models (with hazard ratios [HRs] and 95 % confidence interval [95 %CIs]), and SEMS patency period was examined using the Kaplan – Meier method. SEMS patency was defined as the period between SEMS insertion and the development of recurrent biliary obstruction. Results: 104 patients were included. Median survival time was 281 days; and 85 patients died during a median follow-up period of 320 days. Recurrent biliary obstruction occurred in 35 patients. Median SEMS patency period was 549 days. Multivariable analyses showed that: compared with bile duct carcinoma, gallbladder carcinoma was associated with shorter SEMS patency (HR 8.18, 95 %CI 2.41 – 26.83); patency of left-sided SEMS was inferior to that of bilateral (HR 0.5, 95 %CI 0.32 – 0.93) and right-sided SEMS (HR 0.1, 95 %CI 0.02 – 0.65). Cholangitis before SEMS placement increased the risk of recurrent biliary obstruction (HR 11.44; 95 %CI 4.48 – 32.35) and reduced the SEMS patency period (746 vs. 210 days). Conclusion: Gallbladder carcinoma, left-sided stent placement, and cholangitis before SEMS placement are risk factors for recurrent biliary obstruction after SEMS placement.

The serine protease inhibitor Kazal type 1 (SPINK1), also known as pancreatic secretory trypsin inhibitor (PSTI), is a peptide secreted by pancreatic acinar cells. Genetic studies have shown an association between SPINK1 gene variants and chronic pancreatitis or recurrent acute pancreatitis. The aim of this study was to clarify whether the SPINK1 variants affect the level of serum PSTI.One hundred sixty-three patients with chronic pancreatitis or recurrent acute pancreatitis and 73 healthy controls were recruited. Serum PSTI concentrations were determined with a commercial radioimmunoassay kit.Ten patients with the p.N34S variant, 7 with the IVS3+2TC variant, two with both the p.N34S and the IVS3+2TC variants, and one with the novel missense p.P45S variant in the SPINK1 gene were identified. The serum PSTI level in patients with no SPINK1 variants was 14.3 ± 9.6 ng/ml (mean ± SD), and that in healthy controls was 10.7 ± 2.2 ng/ml. The PSTI level in patients carrying the IVS3+2TC variant (5.1 ± 3.4 ng/ml), but not in those with the p.N34S variant (8.9 ± 3.5 ng/ml), was significantly lower than that in the patients without the SPINK1 variants and the healthy controls. The serum PSTI level in the patient with the p.P45S variant was 4.9 ng/ml. Low levels of serum PSTI (6.0 ng/ml) showed sensitivity of 80 %, specificity of 97 %, and accuracy of 96 % in the differentiation of IVS3+2TC and p.P45S carriers from non-carriers.Serum PSTI levels were decreased in patients with the IVS3+2TC and p.P45S variants of the SPINK1 gene.