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Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis.Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC.FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16-63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved. The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia.FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

Objectives Gallbladder (GB) wall thickening sometimes occurs in patients with autoimmune pancreatitis (AIP), a condition for which the name, IgG4-related cholecystitis, was proposed. We examined the radiological findings of the GB in patients with IgG4-related diseases and clinical features of patients with GB wall thickening and presented a hypothesis of its pathogenesis. Materials and methods GB wall thickening was defined by thickness ≥ 4 mm. GB wall thickness was examined in 258 patients with IgG4-related disease. Clinical and imaging findings of 200 patients with AIP with and without GB wall thickening were then compared. Results GB wall thickening was detected in 58 patients (29%) with AIP and two patients with isolated IgG4-related sclerosing cholangitis. In the 60 GBs examined, wall thickening was diffuse, with the walls possessing a smooth inner surface. No GB wall thickening was detected among the 56 patients with IgG4-related disease without AIP or IgG4-related sclerosing cholangitis. Bile duct stenosis was detected in 56 patients (97%) with AIP with GB wall thickening. Intraductal ultrasonography indicated cystic duct wall thickening connected to bile duct wall thickening in 11 of 14 (79%) patients with AIP or IgG4-related sclerosing cholangitis with GB wall thickening. Forty-eight patients in whom IgG4-related cholecystitis was diagnosed experienced resolution of the GB wall thickening after receiving steroid therapy. Conclusions Most cases of GB wall thickening in IgG4-related diseases are closely associated with IgG4-related sclerosing cholangitis and may be a manifestation of IgG4-related disease throughout the biliary tract, including the bile duct, cystic duct, and GB.

Here, we report a case of successful surgical resection of expansive-growth acinar cell carcinoma. A 59-year-old man was referred to a local hospital with abdominal distention. CT revealed a large abdominal tumor. Subsequently, he was referred to our hospital. Physical examination showed a large tumor on his left upper abdomen without tenderness. CT revealed an enhanced 18 cm-sized expansive-growth tumor on the left flank, suggesting a primary pancreatic tumor. EUS-FNA yielded a diagnosis of adenocarcinoma. Imaging findings were not typical for pancreatic ductal carcinoma. We performed distal pancreatectomy with splenectomy, transverse colon resection, and proximal gastrectomy. Pathological findings revealed a tumor, measuring 19.5×16.5×15.5 cm, originating from the pancreatic body, positive for trypsin, chymotrypsin, and elastase, consistent with a diagnosis of acinar cell carcinoma, pT3, N0, M0. Four courses of adjuvant chemotherapy with S-1 were provided, and the patient is currently alive without recurrence for 10 months.

Background and study aims Acute obstructive suppurative pancreatic ductitis (AOSPD) is a suppurative pancreatic duct infection with main pancreatic duct (MPD) or accessory pancreatic duct obstruction in the absence of a pancreatic pseudocyst or necrosis, which is experienced usually in chronic pancreatitis. The diagnosis is confirmed by the finding of pancreatic duct obstruction on endoscopic retrograde cholangiopancreatography (ERCP) with evidence of infection, such as a positive pancreatic juice culture or drainage of purulent pancreatic juice. Patients and methods We studied five patients with pancreatic ductal adenocarcinoma (PDAC) and one with chronic myelogenous leukemia (CML), who suffered from AOSPD. Results Of the 281 PDAC and 39 CML patients who we treated in the past 2 years in our hospital, five with PDAC (1.8 %) and one with CML (2.6 %) experienced AOSPD. Each patient had fever, abdominal pain, and increased blood C-reactive protein. Pancreatography found that each patient had a MPD stricture and an upstream dilatation. Four had a disruption of the MPD in the upper stream of the stricture. Nasopancreatic drainage was successfully performed in all patients. Pancreatic juice culture was positive for Klebsiella pneumonia, Enterobacter agerogenes, or Enterococcus cloacae in four patients. Conclusion AOSPD should be considered in pancreatic malignancy with fever and abdominal pain. Prompt diagnosis of AOSPD could avoid shortening of survival of patients with an already poor prognosis by infection.

Objectives Diagnosing high-grade intraepithelial neoplasia without invasion, traditionally referred to as carcinoma in situ (CIS), is essential for improving prognosis. We examined the imaging findings of patients with and without CIS to identify significant aspects for the diagnosis of CIS. Methods Forty-six patients strongly suspected of early pancreatic cancer without nodule on imaging (CIS group, n = 27; non-malignant group, n = 19) were retrospectively evaluated according to ten factors of computed tomography/magnetic resonance imaging (CT/MRI), endoscopic ultrasonography (EUS), and endoscopic retrograde cholangiopancreatography (ERCP) using hierarchical cluster and univariate analyses. Results Two clusters were formed by hierarchical cluster analysis. One cluster consisted of 83.3% CIS cases with similar image findings such as focal pancreatic parenchymal atrophy (FPPA) on CT/MRI, main pancreatic duct (MPD) stricture surrounded by hypoechoic areas on EUS, and MPD stricture with upstream MPD dilation on ERCP. On univariate analysis, the CIS and non-malignant groups had FPPA on CT/MRI in 15 (55.6%) and 3 (15.8%) cases (p = 0.013), and MPD stricture surrounded by hypoechoic areas on EUS in 20 (74.1%) and 4 (21.1%) cases (p = 0.001), respectively. MPD stricture surrounded by hypoechoic areas was observed in 80% (12/15) of CIS cases with FPPA on CT/MRI and correlated with FPPA. Moreover, FPPA and MPD stricture surrounded by hypoechoic areas had histopathologically observed fibrosis or fat replacement due to pancreatic parenchymal atrophy. Conclusions FPPA and MPD stricture surrounded by hypoechoic areas are significant findings for the diagnosis of CIS.

Aim To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis (AIP) patients. Methods We examined thyroid function in 77 patients with type 1 AIP (50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. Results Eight patients (10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine (FT4) and high thyroid stimulating hormone (TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine (FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG4-related disease (IgG4-RD); presence of anti-thyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP. Conclusion Hypothyroidism was observed in 8 (10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.

An 80-year-old woman with pancreatic cancer was admitted with fever and abdominal pain. Blood examinations showed an elevated CRP level. On computed tomography (CT), a pancreatic tumor with a dilated upstream main pancreatic duct (MPD) was seen. Endoscopic retrograde cholangiopancreatography (ERCP) showed the strictured part of the MPD at the head of the pancreas with upstream dilatation. A nasopancreatic drainage tube was placed. Through the tube, purulent pancreatic juice was discharged and culture of the pancreatic juice grew Klebsiella pneumoniae. On the day after ERCP, the patient's condition and the laboratory results improved. The patient's disorder was diagnosed as acute obstructive suppurative pancreatitis with pancreatic cancer.

Self-expandable metallic stents (SEMSs) are used for the management of malignant colorectal obstruction. A patient who underwent colonic uncovered SEMS insertion for extraluminal stenosis in the splenic flexure of the transverse colon due to advanced gastric cancer is herein reported. The patient presented with a fracture of the colonic SEMS 494 days after SEMS insertion. Although various complications of stenting have previously been reported, the details of fractures of colonic SEMSs have not yet been reported. Because the improvement in the prognosis for patients who undergo palliative SEMS insertion leads to long-term SEMS placement, diverse complications can thus be expected, and new events like stent fracture are expected to increase in the future.

Immune checkpoint inhibitors (ICIs) are becoming a standard therapy for non-small-cell lung cancer in the advanced stage. As these ICIs become widely available in clinical practice, immune-related adverse effects will become more common. Here we report a patient with lung adenocarcinoma who was treated with nivolumab and developed obstruction because of biliary inflammation. A 63-year-old Japanese man having lung adenocarcinoma with pleural dissemination complained of epigastric pain on the fifth cycle of nivolumab. Computed tomography showed wall thickening at the lower part of the bile duct and cholecystitis. Endoscopic retrograde cholangiopancreatography was repeatedly performed for drainage and stenting of the bile duct. Biopsies did not show obvious malignancy. Laboratory data on day 85 demonstrated grade 3 elevation of serum alkaline phosphatase, transaminase, and amylase levels. We initiated high-dose oral prednisone, resulting in gradual improvement of symptoms and laboratory data. Follow-up magnetic resonance cholangiopancreatography demonstrated no progression of duct obstruction, which confirmed the absence of biliary malignancy. Combined with results from previous reports, nivolumab may cause extrahepatic cholangitis.

Purpose IgG4-related disease is a systemic disease that affects various organs of the body. Aim of this study is to elucidate the clinical characteristics of IgG4-related rhinosinusitis. Material and methods Clinical features, laboratory findings, radiological and endoscopic findings, associated disease, treatment and prognosis were retrospectively examined in 10 patients with IgG4-related rhinosinusitis. Results The age was 59.1 ± 11.3 years old and male-to-female ratio was 1:1. The chief nasal complaints were hyposmia (n = 4), nasal obstruction (n = 3), and nothing (n = 3). Serum IgG4 levels were elevated in all patients and the value was 740.4 ± 472.4 mg/dl. Other IgG4-related diseases were associated in all 10 patients, including IgG4-related sialadenitis (n = 6), IgG4-related dacryoadenitis (n = 5), and autoimmune pancreatitis (n = 5). Imaging findings on CT/MRI were obstruction of the way of elimination (n = 10), thickening of the sinus mucous membrane (n = 10), and fluid in the sinus (n = 6). All of the cases had bilateral findings. Nasal endoscopic findings were chiefly deviated nasal septum (n = 5), polyps (n = 4), edema of the mucous membrane (n = 3). Histologically, abundant infiltration of IgG4 positive plasma cell and lymphocyte and an elevated IgG4+/IgG+ cell ration was detected in all 8 patients and 5 patients, respectively. Endoscopic sinus surgery was performed in 8 patients. Eight patients were treated with steroid therapy for other associated IgG4-related diseases. Symptoms improved in all 6 patients after an initial treatment (endoscopic surgery (n = 5) and steroids (n = 1)), but one patient suffered relapse. Conclusions IgG4-related rhinosinusitis is a distinct entity of IgG4-related disease, and is associated in patients with multiple IgG4-related diseases.

We present a resected case of annular pancreas in which Wirsung's duct encircled the duodenum and continued directly to the main pancreatic duct in the body and tail. Furthermore, Wirsung's duct coursed along the right side of the lower bile duct near the major duodenal papilla. Histologically, the islets of Langerhans in the annular pancreas were irregular in shape and were characterized by a striking abundance of pancreatic polypeptide (PP)-positive cells. The PP-rich area that encircled the duodenum was fused with the PP-poor area in the head of the pancreas. The following embryological hypothesis is proposed. The tip of the ventral pancreatic anlage adhered to the duodenal wall and stretched to form a ring during clockwise rotation. The rotation was incomplete, and the pancreatic duct did not cross over the lower bile duct. Since there was adequate ventral anlage in the lower part of the head of the pancreas, fusion between the ducts of the ventral and dorsal anlagen did not occur. The tip of the ventral anlage overgrew and adhered to the dorsal anlage, and the annular duct fused with the main duct of the dorsal anlage.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall, usually forming an abnormally long common channel. In PBM, since the long common channel defeats the effect of the sphincter of Oddi, pancreatobiliary reflux frequently occurs, resulting in high rates of biliary tract cancers. We present the case of a 68-year-old female with advanced gallbladder cancer concomitant with bile duct cancer associated with PBM without biliary dilatation that had an extremely rare configuration showing a connecting duct without a long common channel. Pancreatography in the selectively cannulated main pancreatic duct showed the terminal portion of the common bile duct via an abnormal connecting duct. Cholangiography in the selectively cannulated lower bile duct showed the main and accessory pancreatic ducts via the connecting duct. The bile amylase level was markedly elevated. This case of a rare configuration of PBM with a connecting duct without a long common channel is the first such reported case in the English literature.

BACKGROUND In pancreaticobiliary maljunction (PBM), reflux of pancreatic juice and bile produces various pathological conditions in the biliary tract and pancreas. Clinical features according to the classification of PBM by confluence between the distal bile duct and the main pancreatic duct proposed in 2015 were evaluated in children. METHODS Clinical features and complicating diseases according to the PBM classification were evaluated in 168 adult PBM patients. Patency of Santorini duct and associated biliary carcinomas were evaluated in 123 patients. RESULTS Similar to children, there were significant differences in age (P

Serial pancreatic juice aspiration cytologic examination (SPACE) by nasopancreatic tube placement can give us an opportunity to diagnose early-stage pancreatic cancer with higher sensitivity and specificity compared with conventional pancreatic cytology by one-time pancreatic juice aspiration or pancreatic duct brushing. We performed SPACE in a patient with persistent pancreatic duct stricture (PDS) with gradually advancing pancreatic parenchyma atrophy (PPA) in the pancreas tail. The result of SPACE was suggestive of pancreatic carcinoma, and distal pancreatectomy was performed. Histopathological examination of the resected specimen revealed carcinoma in situ of the pancreas. The present case could indicate that any PDS becomes a candidate for SPACE especially in a patient with PPA, although the PDS remains unchanged for a long period.

Rupture of abdominal aneurysms associated with median arcuate ligament syndrome (MALS) is a serious condition and requires accurate diagnosis in a clinical setting. We examined three patients with this condition: two women aged 45 and 71 years, and a 61-year-old man. They complained of abdominal pain and had fluid collection around the duodenum. Plain computed tomography (CT) of the fluid collection revealed hyper density, which suggests the presence of blood. Moreover, contrast-enhanced CT revealed aneurysms in the pancreatic head area. Angiography revealed aneurysms of the branches of the gastroepiploic artery, which were treated by endovascular embolization in all patients. Thus, patients with abdominal pain and high-density fluid collection around the duodenum on plain CT may suffer from hemorrhage following rupture of MALS-associated aneurysms.

High-grade pancreatic intraepithelial neoplasia (HG PanIN)/carcinoma in situ (CIS) in the pancreatic body and tail can induce parenchymal atrophy through chronic inflammatory changes presenting as a Hypoechoic area on EUS (Hypocho) or focal pancreatic parenchymal atrophy (FPPA) on computed tomography (CT) and magnetic resonance imaging (MRI). We herein discussed two patients with a hypoechoic area in the pancreatic head and neck on EUS resembling pancreatic ductal adenocarcinoma (PDAC). The lesions consisted of dense fibrosis and fat infiltration with pancreatic parenchymal atrophy around the HG PanIN/CIS in the main pancreatic duct (MPD), which penetrated the lesion and showed mild stenosis and upstream dilation. CT and MRI were unable to visualize the lesions. A specimen was obtained from one lesion by fine-needle aspiration under EUS (EUS-FNA) guidance for histopathological and cytological analysis, but the tests returned negative for adenocarcinoma. However, serial pancreatic-juice aspiration cytologic examination (SPACE) revealed adenocarcinoma in both lesions, prompting surgical resection. Histopathological examination revealed non-invasive HG PanIN/CIS in the MPD surrounded by dense fibrosis and fat deposition in the area of parenchymal atrophy. The CIS was restricted to the area of parenchymal atrophy.These two cases are noteworthy in illustrating a hypoechoic area appearing on EUS as a tumor-like lesion resembling PDAC. EUS-FNA has recently been used histopathologically to diagnose a pancreatic lesion. However, in the present and similar cases, EUS-FNA can only reveal secondary changes due to CIS unless the pancreatic duct covered by the CIS is accidentally punctured. We should bear in mind that CIS can appear as a hypoechoic area resembling PDAC on EUS, and that SPACE is the best method for diagnosing CIS in such cases.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Because of the excessive length of the common channel in PBM, sphincter action does not directly affect the pancreaticobiliary junction, which allows pancreatic juice to reflux into the biliary tract. According to the results of a nationwide survey, bile duct and gallbladder cancers were found in 6.9 and 13.4 % of adult patients with congenital biliary dilatation, respectively, and in 3.1 and 37.4 % of those with PBM without biliary dilatation, respectively. Biliary tract cancers develop about 15-20 years earlier in patients with PBM than in individuals without PBM; they sometimes develop as double cancers. Carcinogenesis is strongly associated with stasis of bile intermingled with refluxed pancreatic juice. Epithelial cells in the biliary tract of PBM patients are under constant attack from activated pancreatic enzymes, increased secondary bile acids, or other mutagens. This can result in hyperplastic change with increased cell proliferation activity, and in turn, oncogene and/or tumor suppressor gene mutations in the epithelia, leading to the biliary tract carcinogenesis. The carcinogenesis of biliary tract cancer accompanying PBM is considered to involve a hyperplasia-dysplasia-carcinoma sequence induced by chronic inflammation caused by the reflux of pancreatic juice into the biliary tract, which differs from the adenoma-carcinoma sequence or the de novo carcinogenesis associated with biliary tract cancers in the population without PBM. Patients with a relatively long common channel have a similar, albeit slightly lower, risk for gallbladder cancer compared with PBM patients.

An accurate diagnosis should be made before treatment of autoimmune pancreatitis and immunoglobulin G4-related sclerosing cholangitis. Once a diagnosis has been established, steroids are the standard therapy and symptoms are the major indications. Before steroid therapy, obstructive jaundice and hyperglycemia should be controlled. An initial dose of 0.6 mg/kg/d of oral prednisolone is administered for 2 to 4 weeks, and is gradually tapered over 2 to 3 months. After steroid therapy has begun, blood and imaging tests are performed periodically. Patients with a poor response to steroids should be reevaluated on suspicion of malignancy. To prevent relapse, maintenance therapy using low-dose prednisolone (2.5-5 mg/d) for 1 to 3 years is recommended in Japan. Proximal biliary stricture is reported to be a predictor of relapse. Readministration and dose-up of steroids are effective for relapses. In Western countries, immunosuppressive drugs and rituximab have also been shown to be effective. The optimal treatment regimen should be addressed in future randomized, controlled clinical trials.

Backgrounds: Endoscopic ultrasonography (EUS) is used to observe the stricture of the main pancreatic duct (MPD) and in diagnosing pancreatic cancer (PC). We investigate the findings on EUS by referring to the histopathological findings of resected specimens. Materials and Methods: Six patients with carcinoma in situ (CIS) and 30 patients with invasive carcinoma of 20 mm or less were included. The preoperative EUS findings were classified as follows. A1: Simple stricture type—no findings around the stricture; A2: Hypoecho stricture type—localized hypoechoic area without demarcation around the stricture; A3: Tumor stricture type—tumor on the stricture; B: Dilation type—the dilation of the pancreatic duct without a downstream stricture; C: Parenchymal tumor type—tumor located apart from the MPD. Results: Classes A1 and A2 consisted of 2 CISs, and 4 invasive carcinomas included two cases smaller than 5 mm in diameter. Most of the cancers classified as A3 or C were of invasive carcinoma larger than 5 mm in diameter. All cancers classified as B involved CIS. Serial pancreatic-juice aspiration cytologic examination (SPACE) was selected for all types of cases, with a sensitivity of 92.0%, while EUS-guided fine needle aspiration cytology (EUS-FNA) was only useful for invasive carcinoma, and its sensitivity was 66.7%. Conclusions: Stricture without a tumor could be a finding for invasive PC and pancreatic duct dilation without a downstream stricture could be a finding indicative of CIS. Carcinoma smaller than 5 mm in diameter could not be recognized by EUS. SPACE had a high sensitivity for diagnosing small PC.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease that can involve essentially any organ simultaneously or metachronously [1]. It was first proposed as a systemic disease in 2003 by Kamisawa et al. following the recognition that a high percentage of patients with autoimmune pancreatitis (AIP) had extrapancreatic manifestations that shared similar histopathological features consisting of dense infiltration of IgG4-positive plasma cells and lymphocytes and fibrosis [2].

To clarify the clinical characteristics of autoimmune pancreatitis (AIP) in immunoglobulin (Ig)G4-related kidney disease (IgG4-RKD).A total of 92 patients with AIP were divided into an IgG4-RKD-positive group (RKD-P group, n = 13) and an IgG4-RKD-negative group (RKD-N group, n = 79) on the basis of the diagnostic criteria for IgG4-RKD. Clinical characteristics, including: age; sex; the presence of extrapancreatic lesions other than renal lesions, proteinuria, and hematuria; serum concentrations of IgG, IgG4, IgE, and creatinine; and urinary concentrations of liver-type fatty acid binding protein, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase were compared between the RKD-P and RKD-N groups. The clinical course of the RKD-P group was also characterized.The prevalence of extrapancreatic lesions other than renal lesions was significantly higher in the RKD-P group (84.6% vs 43.0%,p0.01). Serum creatinine (1.19 mg/dl versus 0.74 mg/dl, p0.05), urinary β2-microglobulin (6609.8 μg/l vs 265.8 μg/l, p0.05), and the prevalence of proteinuria (30.7% vs 7.6%, p0.05) were significantly higher in the RKD-P group. Nine out of thirteen patients in the RKD-P group had multiple low-density renal lesions on enhanced computed tomography, 3 patients had multiple high-intensity lesions on diffusion-weighted magnetic resonance images, and 1 patient had diffuse thickening of the renal wall, with a smooth intra-luminal surface.Patients who had AIP with IgG4-RKD were more likely to have extrapancreatic lesions other than those in the kidney, and their serum creatinine and urinary β2-microglobulin concentrations were significantly higher than in those without IgG4-RKD.

Purpose Response to steroids is included in the diagnostic criteria for IgG4-related sclerosing cholangitis (IgG4-SC). To assess how to appropriately conduct steroid trials for IgG4-related SC, we examined the clinical pictures of steroid responsiveness in IgG4-SC patients. Material and methods A total of 29 patients with IgG4-SC (lower bile duct involvement, n = 29; hilar/intrahepatic bile duct involvement, n = 6) initially treated with steroids were enrolled in this study. Blood biochemistry was examined at about 5, 10 and 15 days after commencing steroid therapy. Endoscopic retrograde cholangiography (ERC) and magnetic resonance cholangiopancreatography (MRCP) were performed after steroid administration in 18 and 25 patients, respectively. Results In 19 patients without biliary drainage, elevated serum levels of total bilirubin, alanine aminotransferase, and alkaline phosphatase were halved in 50%, 25%, and 44% of patients at about 5 days after starting steroids, and in 17%, 38%, and 44% at about 10 days. Responsiveness to steroids could be evaluated at 1–2 weeks on ERC or MRCP, but response was lower in the hilar/intrahepatic bile duct than in the lower bile duct. Conclusions Steroid responsiveness of IgG4-SC is recommended to be assessed by blood biochemistry at 5 and 10 days and on MRCP and/or ERC at 1–2 weeks after starting steroid.

Background An aberrant right posterior sectoral hepatic duct (PHD) draining into extrahepatic bile duct, gallbladder or cystic duct directly is a common and critical anomaly during cholecystectomy. This study aimed to investigate the frequency of aberrant PHD and describe why PHD is critical. Methods In 753 consecutive patients who underwent laparoscopic cholecystectomy (LC) using our standardized procedure over 9 years, we reinvestigated whether an aberrant PHD was present using preoperative images. A PHD joining the common bile duct through the cranial side of the hilar plate was defined as the supraportal type, and one passing through the caudal side of the right portal vein was defined as the infraportal type. Results Fifty-one (6.8%) patients had aberrant PHD. All of them had the infraportal type, and the cystic duct drained into aberrant PHD in 10 (1.3%) and aberrant PHD drained into the cystic duct in six (0.8%). These 16 most dangerous anomalies were diagnosed before surgery. In all patients with aberrant PHD, LC was completed without any complications. Conclusions It seems possible to identify most aberrant PHD by attention to the infraportal-type PHD, and injury to them can be avoided by exposing a critical view using an appropriate procedure.

A 78-year-old Japanese male was referred to our hospital with a 3-month history of anorexia and right abdominal pain. A colonoscopy showed circumferential narrowing of the ascending colon with deep ulceration. Biopsy was performed, and examination of the specimen demonstrated squamous cell carcinoma. Abdominal computed tomography demonstrated thickening of the wall of the ascending colon, multiple lymph node metastases, multiple liver metastases, and peritoneal dissemination. After right hemicolectomy, histological examination demonstrated adenosquamous carcinoma. Biomarker analysis showed a microsatellite stable, wild-type KRAS gene in exon 2 and BRAF V600E mutation. Despite undergoing intensive chemotherapy, the patient died 5 months postoperatively.

BACKGROUND/AIMS Diffuse or segmental irregular narrowing of the main pancreatic duct (MPD), as observed by endoscopic retrograde cholangiopancreatography (ERCP), is a characteristic feature of autoimmune pancreatitis (AIP). METHODS ERCP findings were retrospectively examined in 40 patients with AIP in whom irregular narrowing of the MPD was detected near the orifice. The MPD opening sign was defined as the MPD within 1.5 cm from the orifice being maintained. The distal common bile duct (CBD) sign was defined as the distal CBD within 1.5 cm from the orifice being maintained. Endoscopic findings of a swollen major papilla and histological findings of specimens obtained from the major papilla were examined in 26 and 21 patients, respectively. RESULTS The MPD opening sign was detected in 26 of the 40 patients (65%). The distal CBD sign was detected in 25 of the 32 patients (78%), which showed stenosis of the lower bile duct. The patients who showed the MPD opening sign frequently showed the distal CBD sign (p=0.018). Lymphoplasmacytic infiltration, but not dense fibrosis, was histologically detected in biopsy specimens obtained from the major papilla. CONCLUSIONS On ERCP, the MPD and CBD adjacent to the major papilla are frequently maintained in patients with AIP involving the pancreatic head. These signs are useful for diagnosing AIP on ERCP. (Gut Liver 2015;9113-117).

Background/Aims: Ulcerative colitis (UC) is sometimes associated with autoimmune pancreatitis (AIP). Infiltration of immunoglobulin G4 (IgG4)-positive plasma cells is sometimes detected in the colonic mucosa of AIP or UC patients. This study aimed to clarify the relation between UC and IgG4. Methods: Associations with UC were reviewed in 85 AIP patients. IgG4 immunostaining was performed on biopsy specimens from the colonic mucosa of 14 AIP and 32 UC patients. Results: UC was confirmed in two cases (type 1 AIP, n=1; suspected type 2 AIP, n=1). Abundant infiltration of IgG4-positive plasma cells in the colonic mucosa was detected in the case of suspected type 2 AIP with UC and two cases of type 1 AIP without colitis. Abundant infiltration of IgG4-positive plasma cells was detected in 10 UC cases (IgG4-present, 31%). Although 72% of IgG4-absent UC patients showed mild disease activity, 70% of IgG4-present patients showed moderate to severe disease activity (p

Background/aims Coexistence of autoimmune pancreatitis (AIP) and pancreatic cancer, elevation of serum IgG4 levels in pancreatic cancer patients, and infiltration of IgG4-positive plasma cells in peritumorous pancreatitis have been described in a few reports. This study examined the relationship between intraductal papillary mucinous neoplasm (IPMN) of the pancreas and peritumorous IgG4-positive lymphoplasmacytic infiltrates. Methods Serum IgG4 levels were measured in 54 patients with IPMN (median 70 years, 26 males and 28 females; 13 main duct type and 41 branch duct type). Histological findings focusing on dense lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis were reviewed, and immunostaining with IgG4 and IgG was performed in 23 surgically resected IPMN cases (18 main duct type and 5 branch duct type). The presence of IgG4-positive plasma cells >10/hpf and an IgG4-positive/IgG-positive plasma cell ratio >40% were considered significant. Results Serum IgG4 levels were elevated in 2 (4%) IPMN patients. Significant infiltration of IgG4-positive plasma cells was detected in 4 IPMN cases (17%). The IgG4-positive/IgG-positive plasma cell ratio was >40% in all 4 cases. In one case with a markedly elevated serum IgG4 level (624 mg/dL), typical lymphoplasmacytic sclerosing pancreatitis (AIP type 1) lesions surrounded the whole IPMN. In the 3 other cases, infiltration of IgG4-positive plasma cells with fibrosis was focally detected mainly in the periductal area around the IPMN. Conclusions In a few patients with IPMNs, IgG4-positive plasma cell infiltration can occur in the peritumorous area. The association of an IPMN with AIP type 1-like changes seems to be exceptional and coincidental.

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

This study was aimed to investigate etiology and clinical profiles of recurrent acute pancreatitis (RAP), particularly from the morphology of the pancreaticobiliary duct system.Pancreaticobiliary morphology was examined in 230 of 381 patients with acute pancreatitis (AP) using endoscopic retrograde cholangiopancreatography. We analyzed factors associated with RAP including the pancreaticobiliary duct system.RAP was diagnosed in 74 patients (19%). Major etiologies of RAP were alcoholic (38%), idiopathic (26%) and pancreaticobiliary malformation (22%). Patients with alcoholic RAP were significantly younger (47.2±11.6 years) than those with gallstone RAP (67.3±16.8; p0.05). RAP with pancreaticobiliary malformation (male-to-female ratio: 1:4.3; p0.01) and gallstone RAP (1:1.7; p0.05) occurred predominantly in females in comparison with alcoholic RAP (1:0.2). Recurrence rate was 80% for AP with pancreaticobiliary malformation, significantly higher than for the others (p0.01). Pancreas divisum was suspected as the etiology of mild RAP in 7 patients. Four RAP patients with pancreas divisum underwent endoscopic minor papilla sphincterotomy and improved. Pancreaticobiliary maljunction with biliary dilatation (choledochal cyst) was suspected as the etiology of mild RAP in 3 patients. The 3 RAP patients with choledochal cyst underwent prophylactic flow diversion surgery with complete resection of the dilated common bile duct, and achieved improvement. High confluence of pancreaticobiliary ducts was suspected as the etiology of mild RAP in 6 patients.Pancreaticobiliary malformation is one of the major causes of RAP. As some of them benefit from endoscopic or surgical treatment, morphology of the pancreaticobiliary duct system should be examined where possible in RAP patients.

Objective To clarify the allergic manifestations in patients with autoimmune pancreatitis (AIP). Methods We assessed 67 AIP patients, before they received steroid therapy, for a past history of allergic disease, the peripheral eosinophil count (n=62) and the serum IgE level (n=53). Allergen-specific IgE antibody serologic assays were performed in 15 patients. Results A positive past history and/or the presence of active allergic disease were found in 24 AIP patients (36%), including 15 patients with acute allergic rhinitis and eight patients with bronchial asthma. Peripheral eosinophilia and elevation of the serum IgE level were detected in 16% (10/62) and 60% (32/53) of the patients, respectively. Allergen-specific IgE antibody serologic assays were positive in 13 patients (87%). There were no differences between the assay-positive and -negative patients regarding the clinical profiles. Conclusion In conclusion, 87% of the 15 AIP patients tested had positive allergen-specific IgE antibody serologic assays. Allergic mechanisms may be related to the occurrence of AIP.

IgG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefaction consisting of fibrosis with dense infiltration of IgG4-positive plasma cells; affecting various organs. A case of IgG4-related sclerosing mesenteritis is reported. A 64-year-old man was admitted to our hospital with a suspected tumor of the small intestine. Abdominal computed tomography demonstrated a 6-cm soft tissue mass in the right lower mesentery compressing the jejunum, which also showed accumulation of fluorodeoxyglucose uptake on fluorine-18 fluorodeoxyglucose positron emission tomography. With a preoperative diagnosis of suspected malignant lymphoma with lymphadenopathy in the mesentery, partial small bowel resection was performed. Macroscopically, a hard mass, including several swollen lymph nodes, was detected in the mesentery. Microscopically, marked fibrosis showing partially storiform pattern, obstructive phlebitis, follicular hyperplasia, and abundant infiltration of IgG4-positive plasma cells were detected. IgG4-related mesenteritis was diagnosed histopathologically, but the serum IgG4 level was 81 mg/dl postoperatively. Five months after the surgery, an 11-cm soft tissue mass involving the left ureter appeared. Histological examination of a biopsy specimen from the retroperitoneal mass showed fibrosis with inflammatory infiltration. Although IgG4-related retroperitoneal fibrosis could not be confirmed histologically, the tumor responded well to steroid therapy.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6 % of adult patients with congenital biliary dilatation (bile duct cancer, 32.1 % vs. gallbladder cancer, 62.3 %) and in 42.4 % of PBM patients without biliary dilatation (bile duct cancer, 7.3 % vs. gallbladder cancer, 88.1 %). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Objective The objective of this study was to evaluate picture of the major and minor duodenal papillae in patients with autoimmune pancreatitis (AIP). Methods Endoscopic features of the major and minor papillae were examined in 59 and 13 patients with AIP. After steroid therapy, changes of the major and minor papillae were observed in 5 and 6 patients. The major and minor papillae were observed with narrow band imaging in 24 and 6 patients. Biopsy specimens from the major (n = 50) and minor (n = 13) papillae were immunostained using an anti-IgG4 antibody. Results Endoscopic features of the major and minor papillae were abnormal in 26 patients (44%; swelling [n = 20] and redness [n = 14]) and 5 patients (38%; swelling [n = 5]). Swelling of the pancreatic head, irregular narrowing of the main pancreatic duct of the pancreatic head, stenosis of the lower bile duct, and abundant infiltration of IgG4-positive plasma cells were more frequent in the patients with an abnormal major papilla compared with those with a normal major papilla. On narrow band imaging, dilated vessels were observed in abnormal papillae. After therapy, swelling of the major and minor papillae improved in all 4 and 2 patients. Conclusions Endoscopic features of the major and minor papillae were abnormal in 44% and 38% of the patients with AIP.

The autoimmune pancreatitis (AIP) seen in Japan occurs preferentially in older men, presents with jaundice in many cases, and is seldom associated with symptoms and signs of acute pancreatitis. Elevated serum IgG4 concentrations are noted in a high proportion of cases, and the pancreas characteristically shows a marked lymphoplasmacytic infiltrate with IgG4-positive plasma cells and fibrosis. This entity has been termed lymphoplasmacytic sclerosing pancreatitis (LPSP) and is now known also as type 1 (IgG4-related) AIP.