Michihiro Yoshida

Clinical significance of extrapancreatic lesions in autoimmune pancreatitis.

Objectives: To clarify the frequency and clinical significance of extrapancreatic lesions in autoimmune pancreatitis (AIP). Methods: The frequency and clinical characteristics of extrapancreatic lesions during the clinical course of AIP were investigated retrospectively in 64 patients with AIP. The predictive factors for relapse of AIP at clinical onset were also examined. Results: Extrapancreatic lesions occurred in 95% (61/64) during the clinical course of AIP. The frequencies of sclerosing cholangitis, sclerosing sialadenitis, retroperitoneal fibrosis, and mediastinal or hilar lymphadenopathy were 84% (54/64), 23% (15/64), 16% (10/64), and 77% (27/35), respectively. Patients with sclerosing sialadenitis or extrapancreatic bile duct sclerosing cholangitis had a significantly higher serum immunoglobulin G concentration than those without (P = 0.005 and P = 0.016, respectively). Univariate analysis revealed that sclerosing sialadenitis (P = 0.005), diffuse pancreatic ductal changes (P = 0.028), and a high serum immunoglobulin G concentration (P = 0.030) at clinical onset of AIP were significant predictive factors for relapse. Multivariate analysis revealed that diffuse pancreatic ductal changes (P = 0.005) and sclerosing sialadenitis (P = 0.012) were significant independent predictive factors for relapse of AIP. Conclusions: The frequency of extrapancreatic lesions with AIP during the clinical course was high. The presence of sclerosing sialadenitis at clinical onset is a significant predictive factor for relapse of AIP.

Predictive factors for pancreatitis and cholecystitis in endoscopic covered metal stenting for distal malignant biliary obstruction

Pancreatitis and cholecystitis are major complications after self‐expandable metal stent (SEMS) placement in distal malignant biliary obstruction. We aimed to clarify predictive factors for pancreatitis and cholecystitis after covered SEMS placement.

Comparison of intraductal ultrasonography findings between primary sclerosing cholangitis and IgG4-related sclerosing cholangitis

Comparisons of intraductal ultrasonography (IDUS) findings between primary sclerosing cholangitis (PSC) and IgG4‐related sclerosing cholangitis (IgG4‐SC) have not been elucidated. We aimed to clarify the differences in transpapillary IDUS findings between PSC and IgG4‐SC.

Clinical differences between mass-forming autoimmune pancreatitis and pancreatic cancer

Abstract Objective. Autoimmune pancreatitis (AIP) needs to be differentiated from pancreatic cancer (PC). We aimed to clarify the findings specific for AIP by comparing the clinical differences between mass-forming AIP and PC. Material and methods. We retrospectively compared 36 patients with mass-forming AIP and 60 with PC without metastasis regarding clinical, imaging, serological, histological differences and other organ involvement (OOI). We evaluated the sensitivity, specificity and accuracy of these findings for the differential diagnosis between AIP and PC. Results. The findings 100% specific for AIP were a capsule-like rim on computed tomography (CT), skipped lesion of main pancreatic duct (MPD) on endoscopic retrograde pancreatography (ERP) or magnetic resonance cholangiopancreatography (MRCP), γ-globulin > 2 g/dl, OOI (extrapancreatic biliary stricture, salivary gland swelling and retroperitoneal fibrosis) and ruling out PC by histopathological findings of endoscopic ultrasonography-guided fine-needle aspiration. The findings over 90% specific were IgG4 > 280 mg/dl (98%), IgG > 1800 mg/dl (97%), maximal diameter of upstream MPD < 5 mm on MRCP (95%) and IgG4 > 135 mg/dl (94%), respectively. Conclusions. Clinical, imaging, serological, histological findings and OOI differed between mass-forming AIP and PC. Capsule-like rim on CT, skipped lesion of MPD on ERP or MRCP, IgG4 > 280 mg/dl, and OOI were highly specific findings for AIP. These findings are useful in the differential diagnosis of mass-forming AIP from PC.

Comparative evaluation of the Japanese diagnostic criteria for autoimmune pancreatitis.

Objectives: The aim of the study was to clarify the problems of the Japanese criteria for autoimmune pancreatitis (AIP) in comparison with the other criteria. Methods: We retrospectively investigated the clinical, imaging, serological, and histopathogic features, together with other organ involvement and response to steroid, in 50 patients with AIP diagnosed on the basis of the Japanese, Korean, HISORt, and Asian criteria. Thirty-five patients with pancreatic cancer were enrolled as a control group. Results: Forty (80%) of 50 patients received a diagnosis of AIP on the basis of the Japanese criteria. Imaging findings and serological parameters fulfilled the Japanese criteria in 40 (80%) and 50 (100%) of the patients. Pathological findings fulfilled the Japanese criteria in 6 (43%) of 14 patients. All of the 10 patients who did not have a diagnosis of AIP did not fulfill the imaging criteria. Serological parameters fulfilled the Japanese criteria in 8 (23%) of 35 patients with pancreatic cancer. The sensitivities of the Japanese, Korean, HISORt, and Asian criteria for AIP were 80%, 86%, 92%, and 82%, respectively. The specificities of those 4 criteria were 89%, 89%, 97%, and 89%, respectively. Conclusions: The low sensitivity of imaging criteria and low specificity of serological criteria were the problems in the Japanese criteria.

A case of advanced-stage sclerosing cholangitis with autoimmune pancreatitis not responsive to steroid therapy.

CONTEXT Autoimmune pancreatitis and sclerosing cholangitis associated with autoimmune pancreatitis respond well to steroid therapy. Some criteria used for the differential diagnosis of autoimmune pancreatitis and sclerosing cholangitis with autoimmune pancreatitis include the response to a steroid trial. CASE REPORT A 68-year-old woman was diagnosed as having type 3 sclerosing cholangitis with autoimmune pancreatitis four years after clinical onset. Seven years after clinical onset, imaging findings revealed multiple pancreatic stones in an atrophic pancreas, stenosis of the main pancreatic duct in the head of the pancreas and upstream dilatation and a longer stretch of stenosis in the hilar hepatic region. We tried steroid therapy in an attempt to ameliorate stenosis of both the bile duct and the pancreatic duct and prevent further progression. Neither lesion responded to steroid therapy. CONCLUSION Advanced-stage sclerosing cholangitis with autoimmune pancreatitis may sometimes be unresponsive to steroid therapy, and this should be borne in mind when attempting a steroid trial for the diagnosis of sclerosing cholangitis with autoimmune pancreatitis. Early administration of steroid is important for the prevention of disease progression.

Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion

BackgroundMembrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear.MethodsWe investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay.ResultsOf the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P < 0.01). The growth of wt-HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells.ConclusionsBoth the function of HB-EGF as an EGFR ligand and a novel signal for HB-EGF-C nuclear translocation induce gastric cancer growth, whereas HB-EGF-C nuclear translocation independently plays a critical role in gastric cancer invasion. The present study demonstrated that HB-EGF-C nuclear translocation might be crucial in gastric cancer invasion. HB-EGF-C nuclear translocation may offer a prognostic marker and a new molecular target for gastric cancer therapy.

Feasibility of endoscopic retrograde cholangiopancreatography-related procedures in hemodialysis patients

The opportunities of endoscopic retrograde cholangiopancreatography (ERCP)‐related procedure for hemodialysis (HD) patients have been increasing recently. However, the complication rate of ERCPs in HD patients has not been evaluated sufficiently. We aimed to clarify the feasibility of ERCPs in HD patients.

Hemosuccus Pancreaticus Associated with Segmental Arterial Mediolysis Successfully Treated by Transarterial Embolization

CONTEXT Hemosuccus pancreaticus, a rare cause of intermittent upper gastrointestinal bleeding, is usually caused by the rupture of an aneurysm associated with chronic pancreatitis. Segmental arterial mediolysis is a rare non-arteriosclerotic, non-inflammatory vascular disease characterized by vacuolization and lysis of the arterial smooth muscle cells. Segmental arterial mediolysis often causes intra-abdominal hemorrhage through aneurysm rupture. To our knowledge, hemosuccus pancreaticus associated with segmental arterial mediolysis has not previously been reported. CASE REPORT A 59-year-old man had suffered from recurrent episodes of epigastric pain and melena. Laboratory data showed mild anemia and an elevated serum amylase level. Upper gastrointestinal endoscopy revealed bloody pancreatic juice exuding from the papilla of Vater. There were no findings suggestive of chronic pancreatitis, such as pancreatic calcification, irregularity of the pancreatic duct and atrophy of the pancreas. Contrast-enhanced computed tomography revealed a large fusiform aneurysm of the middle-distal splenic artery, and dissection of the proximal splenic artery and celiac artery. Leakage of contrast medium from the aneurysm into the main pancreatic duct was also evident. Angiography clearly revealed a fusiform aneurysm of the splenic artery. This was managed successfully by transarterial coil embolization and the patient has subsequently shown no recurrence of epigastric pain or melena. CONCLUSION Segmental arterial mediolysis is a very rare cause of hemosuccus pancreaticus not associated with chronic pancreatitis. Transcatheter arterial embolization is useful for treatment of ruptured aneurysm associated with segmental arterial mediolysis.

Predictive factors for positive diagnosis of malignant biliary strictures by transpapillary brush cytology and forceps biopsy

The diagnostic yields of endoscopic transpapillary brush cytology and forceps biopsies for malignant biliary strictures (MBS) remain unclear and predictive factors for diagnosis have not been established. We aimed to clarify the diagnostic yields of both methods and the predictive factors