Diagnostic criteria for autoimmune pancreatitis in Japan

Autoimmune pancreatitis (AIP) is a particular type of pancreatitis of presumed autoimmune etiology. Currently, AIP should be diagnosed based on combination of clinical, serological, morphological, and histopathological features. When diagnosing AIP, it is most important to differentiate it from pancreatic cancer. Diagnostic criteria for AIP, proposed by the Japan Pancreas Society in 2002 first in the world, were revised in 2006. The criteria are based on the minimum consensus of AIP and aim to avoid misdiagnosing pancreatic cancer as far as possible, but not for screening AIP. The criteria consist of the following radiological, serological, and histopathological items: (1) radiological imaging showing narrowing of the main pancreatic duct and enlargement of the pancreas, which are characteristic of the disease; (2) laboratory data showing abnormally elevated levels of serum γ-globulin, IgG or IgG4, or the presence of autoantibodies; (3) histopathological examination of the pancreas demonstrating marked fibrosis and prominent infiltration of lymphocytes and plasma cells, which is called lymphoplasmacytic sclerosing pancreatitis (LPSP). For a diagnosis of AIP, criterion 1 must be present, together with criterion 2 and/ or criterion 3. However, it is necessary to exclude malignant diseases such as pancreatic or biliary cancer.

Immunoglobulin G4-related gastrointestinal diseases, are they immunoglobulin G4-related diseases?

In immunoglobulin G4(IgG4)-related disease(RD),organ enlargement or nodular lesions consisting of abundant infiltration of lymphocytes and IgG4-positive plasma cells and fibrosis are seen in various organs.Although infiltration of many IgG4-positive plasma cells is detected in the gastric and colonic mucosa and major duodenal papilla of patients with autoimmune pancreatitis,it cannot be diagnosed as a gastrointestinal lesion involved in IgG4-RD,because none of the following is observed in these lesions:a mass-like formation;dense fibrosis;or obliterative phlebitis.Based on our review of the literature,there appear to be two types of IgG4-related gastrointestinal disease.One is a gastrointestinal lesion showing marked thickening of the wall of the esophagus and stomach,consisting of dense fibrosis with abundant infiltration of IgG4-positive plasma cells,which usually show submucosal spreading.The other is an IgG4-related pseudotumor occurring in gastrointestinal regions such as the stomach,colon,and major duodenal papilla,showing polypoid or mass-like lesions.Most solitary IgG4-related gastrointestinal lesions that are not associated with other IgG4-RD appear to be difficult to diagnose.It is of utmost importance to rule out malignancy.However,these lesions may respond to steroid therapy.To avoid unnecessary resection,IgG4-related gastrointestinal diseases should be considered in the differential diagnosis.

Review of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography using several endoscopic methods in patients with surgically altered gastrointestinal anatomy

The endoscopic approach for biliary diseases in patients with surgically altered gastrointestinal anatomy(SAGA) had been generally deemed impractical. However, it was radically made feasible by the introduction of double balloon endoscopy(DBE) that was originally developed for diagnosis and treatments for small-bowel diseases. Followed by the subsequent development of singleballoon endoscopy(SBE) and spiral endoscopy(SE), interventions using several endoscopes for biliary disease in patients with SAGA widely gained an acceptance as a new modality. Many studies have been made on this new technique. Yet, some problems are to be solved. For instance, the mutual unavailability among devices due to different working lengths and channels, and unestablished standardization of procedural techniques can be raised. Additionally, in an attempt to standardize endoscopic procedures, it is important to evaluate biliary cannulating methods by case with existence of papilla or not. A full comprehension of the features of respective scope types is also required. However there are not many papers written as a review. In our manuscript, we would like to evaluate and make a review of the present status of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography applying DBE, SBE and SE for biliary diseases in patients with SAGA for establishment of these modalities as a new technology and further improvement of the scopes and devices.

Appendix is a priming site in the development of ulcerative colitis

AIM: The role of the appendix has been highlighted in the pathogenesis of ulcerative colitis (UC). The aims of this study were to elucidate the immuno-imbalances in the appendix of UC patients, and to clarify the role of the appendix in the development of UC.METHODS: Colonoscopic biopsy specimens of the appendix, transverse colon, and rectum were obtained from 86 patients with UC: active pancotitis (A-Pan; n = 15),active left-sided colitis (A-Lt; n = 25), A-Lt with appendiceal involvement (A-Lt/Ap; n = 10), inactive pancolitis (I-Pan;n = 14), and inactive left-sided colitis (I-Lt; n = 22),and from controls. In the isolated mucosal T cells, the CD4/CD8 ratio and proportion of activated CD4+ T cells were investigated, and compared with controls.RESULTS: In the appendix, the CD4/CD8 ratio significantly increased in A-Lt and A-Lt/Ap. The ratio in the appendix also tended to increase in A-Pan. In the rectum, the ratio significantly increased in all UC groups. Tn the appendix,the proportion of CD4+CD69+ (early activation antigen)T cells significantly increased in all UC groups. Tn the rectum, the proportion of CD4+CD69+ T cells significantly increased only in A-Pan. The proportion of CD4+HLADR+ (mature activation antigen) T cells significantly increased only in the rectum of A-Pan, but not in the other areas of any groups.CONCLUSION: The increased CD4/CD8 ratio and predominant infiltration of CD4+CD69+ T cells in the appendix suggest that the appendix is a priming site in the development of UC.

Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis:A multicenter study in Japan

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.

Consensus of primary care in acute pancreatitis in Japan

在日本的尖锐胰腺炎的发生正在增加并且每百万张人口从 187 ～ 347 个盒子。盒子命运是 0.2% 为对温和中等，并且 9.0% 为在在 2003 的日本的严重尖锐胰腺炎。在日本的胰腺炎的专家做了与尖锐胰腺炎在病人的早管理集中于实际方面的这个文件。尖锐胰腺炎和严厉层化的正确诊断应该为尖锐胰腺炎的诊断用标准在所有病人被做并且多，因素得分系统尽早由胰的难处理的疾病的研究委员会求婚了。与尖锐胰腺炎诊断的所有病人应该在医院里被管理。血压监视，脉搏和呼吸率，体温，时时尿的体积，和血氧饱和水平在如此的病人的管理是必要的。早精力旺盛的静脉内的水和具有最前的重要性稳定循环动力学。有鸦片剂的足够的疼痛地势也是重要的。在严重尖锐胰腺炎，在一个早阶段的抗菌素的预防静脉内的管理被推荐。一旦尖锐胰腺炎的诊断被证实，朊酶禁止者的管理应该被开始。如果没有肠塞痛并且胃肠的流血的清楚的症状，从早舞台用非肠道的营养喂的肠内的联合被推荐。有严重尖锐胰腺炎的病人应该尽早被转移到 ICU 执行象朊酶的连续地区性的动脉的注入那样的特殊措施禁止者和抗菌素，和连续牙齿过敏过滤。日本政府为难处理的疾病作为关于措施的研究的工程之一为严重尖锐胰腺炎盖住医疗保健开销。

A body mass index ≥25 kg/m2 is associated with a poor prognosis in patients with acute pancreatitis: a study of Japanese patients

BACKGROUND:In Asian population, there is limited infor mation on the relevance between obesity and poor outcomes in acute pancreatitis(AP). The objective of this study was to examine the clinical impact of obesity based on body mass index(BMI) on prognosis of AP in Japanese patients.METHODS:A total of 116 patients with AP were enrolled in this study. Univariate and multivariate logistic regression analyses were performed to examine relations between BMI and patients’ outcomes. Additionally, to investigate whether including obesity as a prognostic factor improved the predic tive accuracy of a Japanese prognostic factor score(PF score)a receiver-operating characteristic(ROC) curve analysis of mortality was conducted.RESULTS:Multiple logistic regression analyses revealed that BMI ≥25 kg/m2was associated with a significant higher mor tality [odds ratio(OR)=15.8; 95% confidence interval(CI):1.1-227; P=0.043]. The area under the ROC curve(AUC) for the combination of PF score and BMI ≥25 kg/m2(AUC=0.881;95% CI:0.809-0.952) was higher than that for the PF score alone(AUC=0.820; 95% CI:0.713-0.927)(P=0.034).CONCLUSIONS:The negative impact of a high BMI on the prognosis of AP was confirmed in a Japanese population Including BMI ≥25 kg/m2 as an additional parameter to PF score enhanced the predictive value of the PF score for AP-related mortality.

Effect of biliary obstruction and internal biliary drainage on hepatic cytochrome P450 isozymes in rats

AIM: To investigate the total cytochrome P450 (CYP) content, microsomal mixed-function oxidase (MFO) activity, and expression of mRNAs for various CYP isozymes in a simple rat model of reversible obstructive jaundice. METHODS: Obstructive jaundice was created in male rats by causing bile duct obstruction with polyester tape. In another group of rats, bile duct obstruction was followed by internal biliary drainage after releasing the tape. The expression of various CYP isozyme mRNAs was semi-quantitatively assessed by competitive RT- PCR. RESULTS: The total CYP content and microsomal MFO activity showed a significant decrease after biliary obstruction, but returned to respective control levels after biliary drainage. A marked reduction in the expression of CYP1A2, 2B1/2, 2C11, 2E1, 3A1, and 3A2 mRNA was detected during biliary obstruction, while expression increased significantly toward the control level after biliary drainage. Although expression of CYP4A1 mRNA showed no reduction during biliary obstruction, it still increased significantly after biliary drainage. CONCLUSION: These results suggest that not only obstructive jaundice, but also the subsequent internal biliary drainage may affect regulatory medications of the synthesis of individual CYP isozymes differently.

Endoscopic retrograde pancreatography: When should we do it?

Endoscopic retrograde pancreatography(ERP) is an accurate imaging modality in the diagnosis of pancreatobiliary diseases. However, its use has been substantially reduced due to the invasiveness of procedure, the risk of complications and the widespread availability of non-invasive cross-section imaging techniques(computed tomography, magnetic resonance imaging, and endoscopic ultrasound). Since the introduction of endoscopic sphincterotomy, ERP has transformed from diagnostic method to an almost exclusively therapeutic procedure. Pancreatic duct injection substantially increased the risk of post-ERP pancreatitis(1.6%-15.7%); therefore, according to international guidelines ERP is recommended only in cases where biliary intervention is required. However, the role of ERP in the management of pancreatic diseases is currently not clearly defined, but in some cases the filling of pancreatic duct may provide essential information complementing the results of non-invasive imaging techniques. The aim of this publication is to systematically summarize the literature dealing with the diagnostic yield of ERP. We would like to define the precise indications of ERP and overview a diagnostic protocol of pancreatic diseases depending on international guidelines and the opinion of Hungarian experts, because it may improve the diagnostic accuracy, minimize of burden of patients and reduce the risk of procedure related complications.

Long-term outcomes of autoimmune pancreatitis

Autoimmune pancreatitis(AIP) has been considered a favorable-prognosis disease; however,currently,there is limited information on natural course of AIP during long-term follow-up. Recently published studies regarding the long-term outcomes of AIP has demonstrated the developments of pancreatic stone formation,exocrine insufficiency,and endocrine insufficiency are observed in 5%-41%,34%-82%,and 38%-57% of patients having the disease. Furthermore,the incidence rate of developing pancreatic cancer ranges from 0% to 4.8% during the long-term followup. The event of death from AIP-related complications other than accompanying cancer is likely to be rare. During follow-up of AIP patients,careful surveillance for not only relapse of the disease but also development of complications at regular intervals is needed.

Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

Background:Malignant intraductal papillary mucinous neoplasm(IPMN)has poor prognosis.The carcinogenesis of IPMN is not clear.The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.Methods:By using immunohistochemistry,we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013.We also examined the expression of Ki-67,c-Myc and p-JNK.Results:The median immunostaining index of pSmad3C was 79.2%in low-grade dysplasia,74.9%in highgrade dysplasia,and 42.0%in invasive carcinoma(P<0.01),whereas that of pSmad3L was 3.4%,4.3%,and 42.4%,respectively(P<0.01).There was a negative relationship between the expression of pSmad3C and c-Myc(P<0.001,r=-0.615)and a positive relationship between the expression of pSmad3L and c-Myc(P<0.001,r=0.696).Negative relationship between the expression of pSmad3C and Ki-67(P<0.01,r=-0.610)and positive relationship between the expression of pSmad3L and Ki-67(P<0.01,r=0.731)were confirmed.p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells.The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58(range,0.05–0.93),3.83(range,0.85–5.96),respectively(P=0.02).The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91(range,0–36.9)and 82.1(range,46.2–97.1),respectively(P=0.02).The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9(range 5.7–30.8)and 90.9(range 52.9–98.5),respectively(P=0.02).Conclusions:pSmad3L was upregulated in malignant IPMN.pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

Intrahepatic cholangiocarcinoma diagnosed via endoscopic retrograde cholangiopancreatography with a short double-balloon enteroscope

Endoscopic retrograde cholangiopancreatography (ERCP) using a double-balloon enteroscope (DBE) in patients with bowel reconstruction due to a previous abdominal surgery is now widely accepted. In particular, a short DBE, which has a 2.8-mm working channel and 152-cm working length, is useful for ERCP because of its good rotational and straightening ability and the availability of various conventional ERCP accessories through the working channel. Herein we report a case of intrahepatic cholangiocarcinoma via ERCP with a short DBE. This is the first report in which the pre-cutting and the brush cytological examination were performed successfully under a DBE to diagnose intrahepatic cholangiocarcinoma pathologically. The short DBE allowed us to perform all diagnostic and therapeutic procedures accepted in conventional ERCP in patients with surgically altered anatomies.