The Effect of an Invasive Strategy for Treating Pancreatic Necrosis on Mortality: a Retrospective Multicenter Cohort Study.

BACKGROUND: Infected acute necrotic collections (ANC) and walled-off necrosis (WON) of the pancreas are associated with high mortality. The difference in mortality between open necrosectomy and minimally invasive therapies in these patients remains unclear. METHODS: This retrospective multicenter cohort study was conducted among 44 institutions in Japan from 2009 to 2013. Patients who had undergone invasive treatment for suspected infected ANC/WON were enrolled and classified into open necrosectomy and minimally invasive treatment (laparoscopic, percutaneous, and endoscopic) groups. The association of each treatment with mortality was evaluated and compared. RESULTS: Of 1159 patients with severe acute pancreatitis, 122 with suspected infected ANC or WON underwent the following treatments: open necrosectomy (33) and minimally invasive treatment (89), (laparoscopic three, percutaneous 49, endoscopic 37). Although the open necrosectomy group had a significantly higher mortality on univariate analysis (p = 0.047), multivariate analysis showed no significant associations between open necrosectomy or Charlson index and mortality (p = 0.29, p = 0.19, respectively). However, age (for each additional 10 years, p = 0.012, odds ratio [OR] 1.50, 95% confidence interval [CI] 1.09-2.06) and revised Atlanta criteria-severe (p = 0.001, OR 7.84, 95% CI 2.40-25.6) were significantly associated with mortality. CONCLUSIONS: In patients with acute pancreatitis and infected ANC/WON, age and revised Atlanta criteria-severe classification are significantly associated with mortality whereas open necrosectomy is not. The mortality risk for patients undergoing open necrosectomy and minimally invasive treatment does not differ significantly. Although minimally invasive surgery is generally preferred for patients with infected ANC/WON, open necrosectomy may be considered if clinically indicated.

[A case of non-invasive IPMC with fibrotic lesion-like "tubular complex"].

A 73-year-old man was incidentally diagnosed with a cystic lesion in the pancreatic body. Ultrasonography, abdominal computed tomography, magnetic resonance imaging, endoscopic retrograde cholangiopancreatography, and endoscopic ultrasound were performed, and a nodule was detected in the cystic lesion along with an irregularity of the main pancreatic duct. An initial diagnosis of a mixed-type intraductal papillary mucinous neoplasm was made, and a central pancreatectomy was performed. However, the final diagnosis was altered to non-invasive intraductal papillary mucinous carcinoma (IPMC). The histopathological examination revealed a fibrotic lesion that was similar to "tubular complex" findings observed in mouse models of pancreatic cancer. The fibrotic lesion was placed between the main pancreatic duct lesion and branch-duct cystic lesion. The changes reflected in branch-level stenosis may be caused by IPMC growth.

Japanese guidelines for the management of acute pancreatitis: Japanese Guidelines 2015.

BACKGROUND: Japanese (JPN) guidelines for the management of acute pancreatitis were published in 2006. The severity assessment criteria for acute pancreatitis were later revised by the Japanese Ministry of Health, Labour and Welfare (MHLW) in 2008, leading to their publication as the JPN Guidelines 2010. Following the 2012 revision of the Atlanta Classifications of Acute Pancreatitis, in which the classifications of regional complications of pancreatitis were revised, the development of a minimally invasive method for local complications of pancreatitis spread, and emerging evidence was gathered and revised into the JPN Guidelines. METHODS: A comprehensive evaluation was carried out on the evidence for epidemiology, diagnosis, severity, treatment, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and clinical indicators, based on the concepts of the GRADE system (Grading of Recommendations Assessment, Development and Evaluation). With the graded recommendations, where the evidence was unclear, Meta-Analysis team for JPN Guidelines 2015 conducted an additional new meta-analysis, the results of which were included in the guidelines. RESULTS: Thirty-nine questions were prepared in 17 subject areas, for which 43 recommendations were made. The 17 subject areas were: Diagnosis, Diagnostic imaging, Etiology, Severity assessment, Transfer indication, Fluid therapy, Nasogastric tube, Pain control, Antibiotics prophylaxis, Protease inhibitor, Nutritional support, Intensive care, management of Biliary Pancreatitis, management of Abdominal Compartment Syndrome, Interventions for the local complications, Post-ERCP pancreatitis and Clinical Indicator (Pancreatitis Bundles 2015). Meta-analysis was conducted in the following four subject areas based on randomized controlled trials: (1) prophylactic antibiotics use; (2) prophylactic pancreatic stent placement for the prevention of post-ERCP pancreatitis; (3) prophylactic non-steroidal anti-inflammatory drugs (NSAIDs) for the prevention of post-ERCP pancreatitis; and (4) peritoneal lavage. Using the results of the meta-analysis, recommendations were graded to create useful information. In addition, a mobile application was developed, which made it possible to diagnose, assess severity and check pancreatitis bundles. CONCLUSIONS: The JPN Guidelines 2015 were prepared using the most up-to-date methods, and including the latest recommended medical treatments, and we are confident that this will make them easy for many clinicians to use, and will provide a useful tool in the decision-making process for the treatment of patients, and optimal medical support. The free mobile application and calculator for the JPN Guidelines 2015 is available via http://www.jshbps.jp/en/guideline/jpn-guideline2015.html.

Ocular surface reconstruction using the combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery for severe ocular surface disease.

PURPOSE: To assess the surgical combination of autologous cultivated oral mucosal epithelial transplantation and eyelid surgery used to treat patients with severe ocular surface disease and entropion. DESIGN: Observational case series. METHODS: Three patients with severe thermal and chemical injury were treated by the surgical combination of autologous cultivated oral mucosal epithelial transplantation and everting sutures to correct entropion. Their clinical outcomes and the efficacy of this surgical procedure were assessed. RESULTS: The ocular surfaces were successfully reconstructed with autologous cultivated oral mucosal epithelial sheets and everting sutures without any complications during the operations. In the course of a mean follow-up period of 30 months their clinical outcomes were assessed. Postoperative follow-up showed that the simultaneous everting sutures caused no problems with the cultivated oral mucosal epithelial sheet, and there were no severe complications such as infection or inflammation. During the follow-up period, in 2 of the 3 eyes the ocular surface and eyelid remained stable with no recurrence of entropion. CONCLUSION: This case series presents a surgical approach to treat severely scarred ocular surfaces using the combination of autologous cultivated oral mucosal epithelial transplantation and everting sutures. Clinical outcomes suggest that this combined surgical procedure is a safe and useful method for the treatment of patients with severe ocular surface disease and entropion.

The fatal risk in hepatic artery embolization for hemostasis after pancreatic and hepatic surgery: importance of collateral arterial pathways.

PURPOSE: To assess retrospectively the cause of hepatic failure related to hepatic arterial embolization (HAE) for hemostasis after pancreaticoduodenectomy or hepatic lobectomy. MATERIALS AND METHODS: Between June 1993 and March 2006, Twenty HAEs in 17 patients (15 men, two women; mean age, 64 years) were performed. Angiographic findings, including portal vein stenosis, collateral arterial pathways after HAE, and the difference of embolic materials, were recorded. The morbidity (hepatic failure and abscess) and mortality were detailed according to collateral arterial pathways, portal vein stenosis, and embolic material used. RESULTS: Bleeding was controlled in all patients, although two patients required repeat embolization. Hepatic failure (n = 8) and abscess (n = 2) arose in nine of 20 HAEs. Death occurred after six of eight HAEs complicated by hepatic failure. The morbidity and mortality rates of HAE were 45% and 30%, respectively. Hepatic complication was eight times more likely to occur (P = .005) in cases with no hepatic collaterals involving hepatic, replaced, or accessory hepatic arteries. Death was observed only in the cases without hepatic collaterals (P = .011). The correlation between the embolization outcome and the presence of portal vein stenosis or the difference of embolic materials was not significant (P > .61). CONCLUSIONS: HAE can be used to successfully control bleeding secondary to hepatic arterial rupture. In the absence of hepatic collaterals, collateral circulation distal to the occlusion from nonhepatic sources may be inadequate and lead to hepatic failure after HAE.

Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders.

PURPOSE: To investigate the long-term outcome of autologous cultivated oral mucosal epithelial transplantation (COMET) for the treatment of the scar phase of severe ocular surface disorders. Participants This study involved 19 eyes of 17 patients who received autologous COMET for total limbal stem-cell deficiency. METHODS: Autologous cultivated oral mucosal epithelial sheets were created using amniotic membrane as a substrate. Clinical efficacy was evaluated by best-corrected visual acuity and visual acuity at the postoperative 36th month. The clinical results (clinical conjunctivalisation, corneal opacification, corneal neovascularisation and symblepharon formation) were evaluated and graded on a scale from 0 to 3 according to their severity. Clinical safety was evaluated by the presence of persistent epithelial defects, ocular hypertension and infections. RESULTS: Autologous cultivated oral mucosal epithelial sheets were successfully generated for all 17 patients. All patients were followed up for more than 36 months; the mean follow-up period was 55 months and the longest follow-up period was 90 months. During the long-term follow-up period, postoperative conjunctivalisation and symblepharon were significantly inhibited. All eyes manifested various degrees of postoperative corneal neovascularisation, but it gradually abated and its activity was stable at 6 months after surgery. Best-corrected visual acuity was improved in 18 eyes (95%) during the follow-up periods, and visual acuity at the postoperative 36th month was improved in 10 eyes (53%). CONCLUSIONS: These long-term clinical results strongly support the conclusion that tissue-engineered cultivated oral mucosal epithelial sheets are useful in reconstructing the ocular surface of the scar phase of severe ocular surface disorders.

[Problems of adjuvant chemotherapy with S-1 for gastric cancer].

From results of ACTS-GC,postoperative adjuvant chemotherapy,administration of S-1 for one year has become the standard for gastric cancer of Stage II and III except T1. We inspected problems of adjuvant chemotherapy by S-1 by dose rate, an adverse event,and compliance. For the period from July 2006 to December 2008,among 41 cases of stage II/stage III gastric cancer, S-1 was as started as adjuvant therapy by for 28 cases (68.3%). Among 14 cases (63.6%) considered able to complete S-1 treatment for one year, 7 cases (31.8%) had to have their dose reduced or their administration schedule changed. No adverse event of grade 3/4 was found, but cancellation or reduced dose was necessary due to anorexia, malaise, diarrhea, severe skin reaction, and leukopenia resulting from myelosuppression. Thirteen patients took no S-1, and two (4.9%) of them took UFT, while 11 cases (26.8%) became a no-treatment follow-up group for reasons of age, coexisting symptoms and other reasons. The problem in the future is to improve compliance, and to establish a treatment strategy for patients who do not meet administration criteria and for patients for whom continuation of drug administration is impossible.

Cutting-edge information for the management of acute pancreatitis.

Considering that the Japanese (JPN) guidelines for the management of acute pancreatitis were published in Takada et al. (J HepatoBiliary Pancreat Surg 13:2-6, 2006), doubts will be cast as to the reason for publishing a revised edition of the Guidelines for the management of acute pancreatitis: the JPN guidelines 2010, at this time. The rationale for this is that new criteria for the severity assessment of acute pancreatitis were made public on the basis of a summary of activities and reports of shared studies that were conducted in 2008. The new severity classification is entirely different from that adopted in the 2006 guidelines. A drastic revision was made in the new criteria. For example, about half of the cases that have been assessed previously as being 'severe' are assessed as being 'mild' in the new criteria. The JPN guidelines 2010 are published so that consistency between the criteria for severity assessment in the first edition and the new criteria will be maintained. In the new criteria, severity assessment can be made only by calculating the 9 scored prognostic factors. Severity assessment according to the contrast-enhanced computed tomography (CT) grade was made by scoring the poorly visualized pancreatic area in addition to determining the degree of extrapancreatic progress of inflammation and its extent. Changes made in accordance with the new criteria are seen in various parts of the guidelines. In the present revised edition, post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis is treated as an independent item. Furthermore, clinical indicators (pancreatitis bundles) are presented to improve the quality of the management of acute pancreatitis and to increase adherence to new guidelines.

Post-ERCP pancreatitis.

Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP). Detailed information about the findings of previous studies concerning post-ERCP pancreatitis has not been utilized sufficiently. The purpose of the present article was to present guidelines for the diagnostic criteria of post-ERCP pancreatitis, and its incidence, risk factors, and prophylactic procedures that are supported by evidence. To achieve this purpose, a critical examination was made of the articles on post-ERCP pancreatitis, based on the data obtained by research studies published up to 2009. At present, there are no standardized diagnostic criteria for post-ERCP pancreatitis. It is appropriate that post-ERCP pancreatitis is defined as acute pancreatitis that has developed following ERCP, and its diagnosis and severity assessment should be made according to the diagnostic criteria and severity assessment of the Japanese Ministry of Health, Labour and Welfare. The incidence of acute pancreatitis associated with diagnostic and therapeutic ERCP is 0.4-1.5 and 1.6-5.4%, respectively. Endoscopic papillary balloon dilation is associated with a high risk of acute pancreatitis compared with endoscopic sphincterotomy. It was made clear that important risk factors include dysfunction of the Oddi sphincter, being of the female sex, past history of post-ERCP pancreatitis, and performance of pancreaticography. Temporary prophylactic placement of pancreatic stents in the high-risk group is useful for the prevention of post-ERCP pancreatitis [odds ratio (OR) 3.2, 95% confidence interval (CI) 1.6-6.4, number needed to treat (NNT) 10]. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduction in the development of post-ERCP pancreatitis (OR 0.46, 95% CI 0.32-0.65). Single rectal administration of NSAIDs is useful for the prevention of post-ERCP pancreatitis [relative risk (RR) 0.36, 95% CI 0.22-0.60, NNT 15] and decreases the development of pancreatitis in both the low-risk group (RR 0.29, 95% CI 0.12-0.71) and the high-risk group (RR 0.40, 95% CI 0.23-0.72) of post-ERCP pancreatitis. As for somatostatin, a bolus injection may be most useful compared with short- or long-term infusion (OR 0.271, 95% CI 0.138-0.536, risk difference 8.2%, 95% CI 4.4-12.0%). The usefulness of gabexate mesilate was not apparent in any of the following conditions: acute pancreatitis (control 5.7 vs. 4.8% for gabexate mesilate), hyperamylasemia (40.6 vs. 36.9%), and abdominal pain (1.7 vs. 8.9%). Formulation of diagnostic criteria for post-ERCP pancreatitis is needed. Temporary prophylactic placement of pancreatic stents in the high-risk group offers the most promise as a means of preventing post-ERCP pancreatitis. As for pharmacological attempts, there are high expectations concerning NSAIDs because they are excellent in terms of cost-effectiveness, ease of use, and safety. There was no evidence of effective prophylaxis with the use of protease inhibitors, especially gabexate mesilate.

Therapeutic intervention and surgery of acute pancreatitis.

The clinical course of acute pancreatitis varies from mild to severe. Assessment of severity and etiology of acute pancreatitis is important to determine the strategy of management for acute pancreatitis. Acute pancreatitis is classified according to its morphology into edematous pancreatitis and necrotizing pancreatitis. Edematous pancreatitis accounts for 80-90% of acute pancreatitis and remission can be achieved in most of the patients without receiving any special treatment. Necrotizing pancreatitis occupies 10-20% of acute pancreatitis and the mortality rate is reported to be 14-25%. The mortality rate is particularly high (34-40%) for infected pancreatic necrosis that is accompanied by bacterial infection in the necrotic tissue of the pancreas (Widdison and Karanjia in Br J Surg 80:148-154, 1993; Ogawa et al. in Research of the actual situations of acute pancreatitis. Research Group for Specific Retractable Diseases, Specific Disease Measure Research Work Sponsored by Ministry of Health, Labour, and Welfare. Heisei 12 Research Report, pp 17-33, 2001). On the other hand, the mortality rate is reported to be 0-11% for sterile pancreatic necrosis which is not accompanied by bacterial infection (Ogawa et al. 2001; Bradely and Allen in Am J Surg 161:19-24, 1991; Rattner et al. in Am J Surg 163:105-109, 1992). The Japanese (JPN) Guidelines were designed to provide recommendations regarding the management of acute pancreatitis in patients having a variety of clinical characteristics. This article describes the guidelines for the surgical management and interventional therapy of acute pancreatitis by incorporating the latest evidence for the management of acute pancreatitis in the Japanese-language version of JPN guidelines 2010. Eleven clinical questions (CQ) are proposed: (1) worsening clinical manifestations and hematological data, positive blood bacteria culture test, positive blood endotoxin test, and the presence of gas bubbles in and around the pancreas on CT scan are indirect findings of infected pancreatic necrosis; (2) bacteriological examination by fine needle aspiration is useful for making a definitive diagnosis of infected pancreatic necrosis; (3) conservative treatment should be performed in sterile pancreatic necrosis; (4) infected pancreatic necrosis is an indication for interventional therapy. However, conservative treatment by antibiotic administration is also available in patients who are in stable general condition; (5) early surgery for necrotizing pancreatitis is not recommended, and it should be delayed as long as possible; (6) necrosectomy is recommended as a surgical procedure for infected necrosis; (7) after necrosectomy, a long-term follow-up paying attention to pancreatic function and complications including the stricture of the bile duct and the pancreatic duct is necessary; (8) drainage including percutaneous, endoscopic and surgical procedure should be performed for pancreatic abscess; (9) if the clinical findings of pancreatic abscess are not improved by percutaneous or endoscopic drainage, surgical drainage should be performed; (10) interventional treatment should be performed for pancreatic pseudocysts that give rise to symptoms, accompany complications or increase the diameter of cysts and (11) percutaneous drainage, endoscopic drainage or surgical procedures are selected in accordance with the conditions of individual cases.

An association between asthma and TNF-308G/A polymorphism: meta-analysis.

Tumor necrosis factor (TNF) is a potent inflammatory cytokine that contributes to airway inflammation in asthma. Previous studies have reported that a G-to-A transition at position -308 (-308G/A, also referred to as TNF-alpha-308*1 and 308*2 respectively), is associated with asthma, but other studies have shown conflicting results. To investigate a possible association between the TNF-308G/A polymorphism and asthma, we performed transmission disequilibrium tests and a case-control study (family samples: 495 members in 165 Japanese trio families with one asthmatic child and both parents; case-control samples: 461 Japanese asthmatic children and 465 healthy controls). To increase the sample size and power, we performed a meta-analysis of all available relevant studies, including 2,477 asthmatics and 3,217 controls. We did not find a significant association between the TNF-308G/A polymorphism and childhood atopic asthma in two independent Japanese populations (P>0.05); however, meta-analysis revealed that the TNF-308G/A polymorphism was statistically significantly associated with asthma. The combined odds ratio with a fixed effects model and with a random effects for TNF-308A was 1.46 (95% confidence interval [CI], 1.27-1.68, P=0.0000001) and 1.46 (95% CI, 1.20-1.77, P=0.00014) respectively. Our data further support the importance of the TNF region in the development of asthma.

JPN Guidelines for the management of acute pancreatitis: cutting-edge information.

The JPN Guidelines for the Management of Acute Pancreatitis are organized under the subject headings: epidemiology, diagnosis, management strategy, severity assessment and transfer criteria, management of gallstone pancreatitis, nonsurgical management, and surgical management. The Guidelines contain cutting-edge information on each of these subjects, as well as a section on the Japanese medical insurance system which provides information that should prove useful to physicians in other countries. The quality of the evidence was evaluated by the evidence-based classification method used at the Cochrane Library. The levels of recommendation of the individual management methods contained in the Guidelines were determined on the basis of the evaluation of evidence by the consensus of the members of the Working Group (see below). The Japanese Society for Abdominal Emergency Medicine, the Japan Pancreas Society, and the Research Group for Intractable Diseases and Refractory Pancreatic Diseases (which is sponsored by the Japanese Ministry of Health, Labour, and Welfare) were commissioned to produce the JPN Guidelines for the Management of Acute Pancreatitis. A Working Group of 20 physicians specializing in pancreatic diseases and emergency medicine investigated and analyzed 14821 cases retrieved by means of a Medline (1960-2004) search and discussed the available literature on acute pancreatitis (limited to human pancreatitis). The Working Group held many general discussions in order to reach a consensus on the content of the Guidelines. After producing a draft, the Publishing Committee of the JPN Guidelines for the Management of Acute Pancreatitis posted it on a website and asked for comments and criticisms. Subsequently, a final version of the Guidelines was published in Japanese in 2003. The Publishing Committee is now making the Guidelines available to a much wider readership by bringing out an English version.

Health insurance system and payments provided to patients for the management of severe acute pancreatitis in Japan.

The health insurance system in Japan is based upon the Universal Medical Care Insurance System, which gives all citizens the right to join an insurance scheme of their own choice, as guaranteed by the provisions of Article 25 of the Constitution of Japan, which states: "All people shall have the right to maintain the minimum standards of wholesome and cultured living." The health care system in Japan includes national medical insurance, nursing care for the elderly, and government payments for the treatment of intractable diseases. Medical insurance provisions are handled by Employee's Health Insurance (Social Insurance), which mainly covers employees of private companies and their families, and by National Health Insurance, which provides for the needs of self-employed people. Both schemes have their own medical care service programs for retired persons and their families. The health care system for the elderly covers people 75 years of age and over and bedridden people 65 years of age and over. There is also a system under which the government pays all or part of medical expenses, and/or pays medical expenses not covered by insurance. This is referred to collectively as the "medical expenses payment system" and includes the provision of medical assistance for specified intractable diseases. Because severe acute pancreatitis has a high mortality rate, it is specified as an intractable disease. In order to lower the mortality rate of various diseases, including severe acute pancreatitis, the specification system has been adopted by the government. The cost of treatment for severe acute pancreatitis is paid in full by the government from the date the application is made for a certificate verifying that the patient has an intractable disease.

JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for acute pancreatitis.

The currently used diagnostic criteria for acute pancreatitis in Japan are presentation with at least two of the following three manifestations: (1) acute abdominal pain and tenderness in the upper abdomen; (2) elevated levels of pancreatic enzyme in the blood, urine, or ascitic fluid; and (3) abnormal imaging findings in the pancreas associated with acute pancreatitis. When a diagnosis is made on this basis, other pancreatic diseases and acute abdomen can be ruled out. The purpose of this article is to review the conventional criteria and, in particular, the various methods of diagnosis based on pancreatic enzyme values, with the aim of improving the quality of diagnosis of acute pancreatitis and formulating common internationally agreed criteria. The review considers the following recommendations: Better even than the total blood amylase level, the blood lipase level is the best pancreatic enzyme for the diagnosis of acute pancreatitis and its differentiation from other diseases. A pivotal factor in the diagnosis of acute pancreatitis is identifying an increase in pancreatic enzymes in the blood. Ultrasonography (US) is also one of the procedures that should be performed in all patients with suspected acute pancreatitis. Magnetic resonance imaging (MRI) is one of the most important imaging procedures for diagnosing acute pancreatitis and its intraperitoneal complications. Computed tomography (CT) is also one of the most important imaging procedures for diagnosing acute pancreatitis and its intraabdominal complications. CT should be performed when a diagnosis of acute pancreatitis cannot be established on the basis of the clinical findings, results of blood and urine tests, or US, or when the etiology of the pancreatitis is unknown. When acute pancreatitis is suspected, chest and abdominal X-ray examinations should be performed to determine whether any abnormal findings caused by acute pancreatitis are present. Because the etiology of acute pancreatitis can have a crucial influence on both the treatment policy and severity assessment, it should be evaluated promptly and accurately. It is particularly important to differentiate between gallstone-induced acute pancreatitis, which requires treatment of the biliary system, and alcohol-induced acute pancreatitis, which requires a different form of treatment.

JPN Guidelines for the management of acute pancreatitis: epidemiology, etiology, natural history, and outcome predictors in acute pancreatitis.

Acute pancreatitis is a common disease with an annual incidence of between 5 and 80 people per 100,000 of the population. The two major etiological factors responsible for acute pancreatitis are alcohol and cholelithiasis (gallstones). The proportion of patients with pancreatitis caused by alcohol or gallstones varies markedly in different countries and regions. The incidence of acute alcoholic pancreatitis is considered to be associated with high alcohol consumption. Although the incidence of alcoholic pancreatitis is much higher in men than in women, there is no difference in sexes in the risk involved after adjusting for alcohol intake. Other risk factors include endoscopic retrograde cholangiopancreatography, surgery, therapeutic drugs, HIV infection, hyperlipidemia, and biliary tract anomalies. Idiopathic acute pancreatitis is defined as acute pancreatitis in which the etiological factor cannot be specified. However, several studies have suggested that this entity includes cases caused by other specific disorders such as microlithiasis. Acute pancreatitis is a potentially fatal disease with an overall mortality of 2.1%-7.8%. The outcome of acute pancreatitis is determined by two factors that reflect the severity of the illness: organ failure and pancreatic necrosis. About half of the deaths in patients with acute pancreatitis occur within the first 1-2 weeks and are mainly attributable to multiple organ dysfunction syndrome (MODS). Depending on patient selection, necrotizing pancreatitis develops in approximately 10%-20% of patients and the mortality is high, ranging from 14% to 25% of these patients. Infected pancreatic necrosis develops in 30%-40% of patients with necrotizing pancreatitis and the incidence of MODS in such patients is high. The recurrence rate of acute pancreatitis is relatively high: almost half the patients with acute alcoholic pancreatitis experience a recurrence. When the gallstones are not treated, the risk of recurrence in gallstone pancreatitis ranges from 32% to 61%. After recovering from acute pancreatitis, about one-third to one-half of acute pancreatitis patients develop functional disorders, such as diabetes mellitus and fatty stool; the incidence of chronic pancreatitis after acute pancreatitis ranges from 3% to 13%. Nevertheless, many reports have shown that most patients who recover from acute pancreatitis regain good general health and return to their usual daily routine. Some authors have emphasized that endocrine function disorders are a common complication after severe acute pancreatitis has been treated by pancreatic resection.

JPN Guidelines for the management of acute pancreatitis: medical management of acute pancreatitis.

The basic principles of the initial management of acute pancreatitis are adequate monitoring of vital signs, fluid replacement, correction of any electrolyte imbalance, nutritional support, and the prevention of local and systemic complications. Patients with severe acute pancreatitis should be transferred to a medical facility where adequate monitoring and intensive medical care are available. Strict cardiovascular and respiratory monitoring is mandatory for maintaining the cardiopulmonary system in patients with severe acute pancreatitis. Maximum fluid replacement is needed to stabilize the cardiovascular system. Prophylactic antibiotic administration is recommended to prevent infectious complications in patients with necrotizing pancreatitis. Although the efficacy of the intravenous administration of protease inhibitors is still a matter of controversy, there is a consensus in Japan that a large dose of a synthetic protease inhibitor should be given to patients with severe acute pancreatitis in order to prevent organ failure and other complications. Enteral feeding is superior to parenteral nutrition when it comes to the nutritional support of patients with severe acute pancreatitis. The JPN Guidelines recommend, as optional measures, blood purification therapy and continuous regional arterial infusion of a protease inhibitor and antibiotics, depending on the patient's condition.

JPN Guidelines for the management of acute pancreatitis: severity assessment of acute pancreatitis.

This article addresses the criteria for severity assessment and the severity scoring system of the Ministry of Health and Welfare of Japan; now the Japanese Ministry of Health, Labour, and Welfare (the JPN score). It also presents data comparing the JPN score with the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Ranson score, which are the major measuring scales used in the United States and Europe. The goal of investigating these scoring systems is the achievement of earlier diagnosis and more appropriate and successful treatment of severe or moderate acute pancreatitis, which has a high mortality rate. This article makes the following recommendations in terms of assessing the severity of acute pancreatitis: (1) Severity assessment is indispensable to the selection of proper initial treatment in the management of acute pancreatitis (Recommendation A). (2) Assessment by a severity scoring system (JPN score, APACHE II score) is important for determining treatment policy and identifying the need for transfer to a specialist unit (Recommendation A). (3) C-reactive protein (CRP) is a useful indicator for assessing severity (Recommendation A). (4) Contrast-enhanced computed tomography (CT) scanning and contrast-enhanced magnetic resonance imaging (MRI) play an important role in severity assessment (Recommendation A). (5) A JPN score of 2 or more (severe acute pancreatitis) has been established as the criterion for hospital transfer (Recommendation A). (6) It is preferable to transfer patients with severe acute pancreatitis to a specialist medical institution where they can receive continuous monitoring and systemic management.

JPN Guidelines for the management of acute pancreatitis: surgical management.

Acute pancreatitis represents a spectrum of disease ranging from a mild, self-limited course to a rapidly progressive, severe illness. The mortality rate of severe acute pancreatitis exceeds 20%, and some patients diagnosed as mild to moderate acute pancreatitis at the onset of the disease may progress to a severe, life-threatening illness within 2-3 days. The Japanese (JPN) guidelines were designed to provide recommendations regarding the management of acute pancreatitis in patients having a diversity of clinical characteristics. This article sets forth the JPN guidelines for the surgical management of acute pancreatitis, excluding gallstone pancreatitis, by incorporating the latest evidence for the surgical management of severe pancreatitis in the Japanese-language version of the evidence-based Guidelines for the Management of Acute Pancreatitis published in 2003. Ten guidelines are proposed: (1) computed tomography-guided or ultrasound-guided fine-needle aspiration for bacteriology should be performed in patients suspected of having infected pancreatic necrosis; (2) infected pancreatic necrosis accompanied by signs of sepsis is an indication for surgical intervention; (3) patients with sterile pancreatic necrosis should be managed conservatively, and surgical intervention should be performed only in selected cases, such as those with persistent organ complications or severe clinical deterioration despite maximum intensive care; (4) early surgical intervention is not recommended for necrotizing pancreatitis; (5) necrosectomy is recommended as the surgical procedure for infected pancreatic necrosis; (6) simple drainage should be avoided after necrosectomy, and either continuous closed lavage or open drainage should be performed; (7) surgical or percutaneous drainage should be performed for pancreatic abscess; (8) pancreatic abscesses for which clinical findings are not improved by percutaneous drainage should be subjected to surgical drainage immediately; (9) pancreatic pseudocysts that produce symptoms and complications or the diameter of which increases should be drained percutaneously or endoscopically; and (10) pancreatic pseudocysts that do not tend to improve in response to percutaneous drainage or endoscopic drainage should be managed surgically.

JPN Guidelines for the management of acute pancreatitis: treatment of gallstone-induced acute pancreatitis.

Gallstones, along with alcohol, are one of the primary etiological factors of acute pancreatitis, and knowledge of the etiology as well as the diagnosis and management of gallstones, is crucial for managing acute pancreatitis. Because of this, evidence regarding the management of gallstone-induced pancreatitis in Japan was collected, and recommendation levels were established by comparing current clinical practices with optimal clinical practices. The JPN Guidelines for managing gallstone-induced acute pancreatitis recommend two procedures: (1) an urgent endoscopic procedure should be performed in patients in whom biliary duct obstruction is suspected and in patients complicated by cholangitis (Recommendation A); and (2) after the attack of gallstone pancreatitis has subsided, a laparoscopic cholecystectomy should be performed during the same hospital stay (Recommendation B).

Management strategy for acute pancreatitis in the JPN Guidelines.

The diagnosis of acute pancreatitis is based on the following findings: (1) acute attacks of abdominal pain and tenderness in the epigastric region, (2) elevated blood levels of pancreatic enzymes, and (3) abnormal diagnostic imaging findings in the pancreas associated with acute pancreatitis. In Japan, in accordance with criteria established by the Japanese Ministry of Health, Labour, and Welfare, the severity of acute pancreatitis is assessed based on the clinical signs, hematological findings, and imaging findings, including abdominal contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI). Severity must be re-evaluated, especially in the period 24 to 48 h after the onset of acute pancreatitis, because even cases diagnosed as mild or moderate in the early stage may rapidly progress to severe. Management is selected according to the severity of acute pancreatitis, but it is imperative that an adequate infusion volume, vital-sign monitoring, and pain relief be instituted immediately after diagnosis in every patient. Patients with severe cases are treated with broad-spectrum antimicrobial agents, a continuous high-dose protease inhibitor, and continuous intraarterial infusion of protease inhibitors and antimicrobial agents; continuous hemodiafiltration may also be used to manage patients with severe cases. Whenever possible, transjejunal enteral nutrition should be administered, even in patients with severe cases, because it seems to decrease morbidity. Necrosectomy is performed when necrotizing pancreatitis is complicated by infection. In this case, continuous closed lavage or open drainage (planned necrosectomy) should be the selected procedure. Pancreatic abscesses are treated by surgical or percutaneous drainage. Emergency endoscopic procedures are given priority over other methods of management in patients with acute gallstone-associated pancreatitis, patients suspected of having bile duct obstruction, and patients with acute gallstone pancreatitis complicated by cholangitis. These strategies for the management of acute pancreatitis are shown in the algorithm in this article.