Management of acute pancreatitis in Japan: Analysis of nationwide epidemiological survey.

Acute pancreatitis (AP) is an acute inflammatory disease of the exocrine pancreas. In Japan, nationwide epidemiological surveys have been conducted every 4 to 5 years by the Research Committee of Intractable Pancreatic Diseases, under the support of the Ministry of Health, Labour, and Welfare of Japan. We reviewed the results of the nationwide surveys focusing on the severity assessment and changes in the therapeutic strategy for walled-off necrosis. The severity assessment system currently used in Japan consists of 9 prognostic factors and the imaging grade on contrast-enhanced computed tomography. By univariate analysis, all of the 9 prognostic factors were associated with AP-related death. A multivariate analysis identified 4 out of the 9 prognostic factors (base excess or shock, renal failure, systemic inflammatory response syndrome criteria, and age) that were associated with AP-related death. Receiver-operating characteristics curve analysis showed that the area under the curve was 0.82 for these 4 prognostic factors and 0.84 for the 9 prognostic factors, suggesting the comparable utility of these 4 factors in the severity assessment. We also examined the temporal changes in treatment strategy for walled-off necrosis in Japan according to the 2003, 2007, and 2011 surveys. Step-up approaches and less-invasive endoscopic therapies were uncommon in 2003 and 2007, but became popular in 2011. Mortality has been decreasing in patients who require intervention for walled-off necrosis. In conclusion, the nationwide survey revealed the comparable utility of 4 prognostic factors in the severity assessment and the increased use of less-invasive, step-up approaches with improved clinical outcomes in the management of walled-off necrosis.

Gender difference in gastro-esophageal reflux diseases.

The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Recent advances in autoimmune pancreatitis: type 1 and type 2.

Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis characterised clinically by frequent presentation with obstructive jaundice, histologically by a lymphoplasmacytic infiltrate with fibrosis, and therapeutically by a dramatic response to steroids. When so defined, AIP can be sub-classified into two subtypes, 1 and 2. Recent international consensus diagnostic criteria for AIP have been developed for diagnosis of both forms of AIP. Type 1 AIP is the pancreatic manifestation of a multiorgan disease, recently named IgG4-related disease. Little is known about the pathogenesis of either form of AIP. Despite frequent association of type 1 AIP with elevated serum IgG4 levels and infiltration with IgG4-positive plasma cells, it is unlikely that IgG4 plays a pathogenic role in AIP. Type 1 AIP responds to steroids, but there needs to be consensus on treatment regimens for induction and therapeutic end points. Relapses are common, but can be reduced by long-term use of low-dose steroids. Recent reports suggest that immunomodulators (azathioprine, 6-mercaptopurine and mycophenolate mofetil), as well biological agents (the antibody to CD20, rituximab) may have a role in maintaining remission in relapsing type 1 AIP. Future studies should clarify the best management options for treatment of relapses and maintenance of remission. Type 2 AIP is a pancreas-specific disorder not associated with IgG4. It presents in younger individuals equally with obstructive jaundice and pancreatitis. The inflammatory process responds to steroid therapy; relapses are uncommon. The clinical spectrum and long-term outcomes of medically treated type 2 AIP are still being evaluated.

Long-period pancreatic stenting for painful chronic calcified pancreatitis required higher medical costs and frequent hospitalizations compared with surgery.

OBJECTIVES: The aim of this study was to compare the benefits between endoscopic drainage and surgical drainage of the pancreatic duct for patients with chronic calcified pancreatitis. METHODS: A total of 68 patients were classified into endoscopic (n = 34) or surgical (n = 34) treatment groups. Patients receiving endoscopic treatment were further divided into 2 subgroups: a short-period group, patients who could discontinue serial pancreatic stenting within 1 year (n = 19); and a long-period group, patients who needed pancreatic drainage by serial endoscopic stenting for more than 1 year (n = 15). The medical records of these patients were retrospectively analyzed. RESULTS: Hospital stays, frequency of hospitalizations, and medical expense were similar between the short-period endoscopic treatment group and surgery group. On the other hand, patients in the long-period endoscopic treatment group required significantly longer hospital stays, more frequent hospitalizations, and had higher medical expenses than the short-period endoscopic treatment group as well as than the surgery group. CONCLUSIONS: Patients who underwent serial endoscopic stenting for more than 1 year showed no benefit compared with surgical treatment in terms of the frequency of hospital stays and medical costs.

Clinical characteristics of 327 Asian patients with autoimmune pancreatitis based on Asian diagnostic criteria.

OBJECTIVES: To clarify the clinical and pathophysiological characteristics of autoimmune pancreatitis (AIP) in Asia. METHODS: A retrospective, actual situation survey of AIP diagnosed by Asian criteria was conducted in 10 centers of Japan, Korea, Taiwan, China, and India. RESULTS: A total of 327 AIP cases (258 male and 69 female subjects; average age, 60.0 years) were enrolled. Obstructive jaundice was the most frequent initial symptom (46%-74%), followed by weight loss (4%-51%) and abdominal pain (19%-44%). Diffuse swelling of the pancreas was frequent in Japan (64%) and Korea (81%), but segmental swelling of the pancreas was more frequent in Taiwan (70%) and China (72%) (P < 0.01). Serum immunoglobulin G4 levels were elevated in 58%-100% of cases in Japan, Korea, and Taiwan. Pathologically, almost all AIPs in Asia were lymphoplasmacytic sclerosing pancreatitis. Sclerosing cholangitis was the most frequent extrapancreatic lesion (60%-81%). Steroid therapy was a major and effective therapeutic strategy in Japan, Korea, and Taiwan. However, the rate of resection or bypass operation was higher in Taiwan (40%) and China (72%) (P < 0.01). CONCLUSIONS: Features of AIP are fundamentally similar in Japan, Korea, Taiwan, and China. Knowledge of emerging AIP should be more widespread in Asia to avoid unnecessary operation.

Intraductal papillary mucininous neoplasm of the bile ducts: multimodality assessment with pathologic correlation.

Mucin-producing intraductal papillary neoplasm (adenocarcinoma/adenoma) in the bile duct is becoming recognized as a specific type of neoplasm. Since, it bears a striking similarity to intraductal papillary mucinous neoplasms of the pancreas with regard to its histopathologic features, the term "intraductal papillary mucinous neoplasms of the bile duct" (IPMN-B) is frequently used, although no definite terminology or definition has been decided by World Health Organization. This neoplasm lacks ovarian-like stroma and communicates with the bile ducts, unlike biliary mucinous cystic neoplasm (MCN). On the other hand, malignant IPMN-B is categorized as an intraductal-growth type of intrahepatic cholangiocarcinoma (ICC). In comparison to other types of ICC, such as the mass-forming type and periductal-infiltrating type that have poor resectability and an unfavorable prognosis, malignant IPMN-B can be resected and demonstrates a more favorable prognosis. Meanwhile, unlike biliary MCN that is usually confined in a closed cyst, IPMN-B can spread along the mucosal surface of the bile ducts, and it should be widely resected. Therefore, multimodality assessment is needed to ensure the correct diagnosis of IPMN-B. We herein review the imaging findings of IPMN-B with pathologic correlation.

Assessment of severity of acute pancreatitis according to new prognostic factors and CT grading.

The assessment of severity at the initial medical examination plays an important role in introducing adequate early treatment and the transfer of patients to a medical facility that can cope with severe acute pancreatitis. Under these circumstances, "criteria for severity assessment" have been prepared in various countries, including Japan, and these criteria are now being evaluated. The criteria for severity assessment of acute pancreatitis in Japan were determined in 1990 (of which a partial revision was made in 1999). In 2008, an overall revision was made and the new Japanese criteria for severity assessment of acute pancreatitis were prepared. In the new criteria for severity assessment, the diagnosis of severe acute pancreatitis can be made according to 9 prognostic factors and/or the computed tomography (CT) grades based on contrast-enhanced CT. Patients with severe acute pancreatitis are expected to be transferred to a specialist medical center or to an intensive care unit to receive adequate treatment there. In Japan, severe acute pancreatitis is recognized as being a specified intractable disease on the basis of these criteria, so medical expenses associated with severe acute pancreatitis are covered by Government payment.

The model for end-stage liver disease score is useful for predicting economic outcomes in adult cases of living donor liver transplantation.

BACKGROUND: The model for end-stage liver disease (MELD) is useful for assessing the recipients of liver transplants, namely, deceased-donor transplantation. The application of MELD for living donor liver transplantation (LDLT) is under investigation. Thus, the aim of this study was to analyze the impact of the MELD score in LDLT in Japan. METHODS: Seventeen adult cases of LDLT during 2001 to 2005 were enrolled. Indications for LDLT were primary biliary cirrhosis, seven; liver cirrhosis, two; hepatocellular carcinoma (HCC), three; metabolic liver disease, one; primary sclerosing cholangitis, two; Caroli's disease, one; and biliary atresia, one. Total medical charges during the operative periods were retrospectively evaluated. The united network of organ sharing (UNOS) modified was obtained using preoperative clinical data. RESULTS: The average medical expense of the 17 cases was approximately 97,901 US dollar. The UNOS-modified MELD score was 22.1. A statistically significant positive correlation was found between the MELD score and medical expense (P = 0.0086, rho = 0.657), and between the MELD score and the length of stay in the intensive care unit (ICU) (P = 0.0396, rho = 0.515). The cause of the liver disease leading to transplantation was not related to MELD score, medical expense, or length of ICU stay. CONCLUSIONS: Although not originally designed for the application to LDLT, the MELD score is useful for predicting medical expenses in LDLT. Similar to those of deceased-donor liver transplantation, the disadvantage of high medical expenses associated with a high MELD score allow consideration of an earlier elective operation in suitable cases.