With regards to Medical Treatment in the Japanese (JPN) guidelines for the management of acute pancreatitis, clinical questions (CQ) were set in the field of pain control, antibiotics prophylaxis, anti-fungus prophylaxis, and protease inhibitor or administration of histamine H2 receptor blocker. In this article, we describe revisions made in the JPN guidelines 2015 with regards to these items from the 2010 version. Many recent reports have shown that the prophylactic administration of antibiotics used for acute pancreatitis is not effective. In the JPN guidelines 2015, the Meta-analysis team of the guideline committee performed their own analysis and proposed new recommendations dependent on the results from antibiotics prophylaxis. The efficacy of continuous high-dose intravenous administration of protease inhibitor for severe acute pancreatitis should be discussed through large scaled, high quality RCTs.

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A number of clinical observational studies providing evidence for the efficacy of continuous regional arterial infusion (CRAI) therapy for severe acute pancreatitis (SAP), including a randomized controlled trial have been collected since 1996. On the other hand, a recent clinical study (propensity score matching analysis) using DPC data showed no significant difference between CRAI group and non-CRAI group in mortality rate and incidence of intervention. The Revision Committee of the Japanese Guidelines for the management of acute pancreatitis downgraded the recommendation for CRAI therapy because efficacy of CRAI for severe acute pancreatitis has not been confirmed.

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If acute pancreatitis progresses to a severe state, the resulting intra-abdominal pressure (IAP) can cause severe complications. WSACS has defined a sustained or repeated IAP ≥12mmHg as IAH and a sustained IAP >20mmHg associated with new organ dysfunction/failure as abdominal compartment syndrome (ACS). The incidence of ACS was 4%-6%, the mortality rate was 47.5% with a high incidence of organ failure, and the incidence of complications including sepsis and secondary pancreatic infection was high. Therefore, if CT findings showing fluid collection at multiple sites, massive fluid resuscitation, and renal and/or respiratory dysfunction are obtained, the IAP (trans-bladder technique) should be monitored over time. Medical treatment for IAH/ACS consists of gastrointestinal decompression, intra-abdominal decompression, improved abdominal wall compliance, optimized fluid administration, and optimized systemic/regional perfusion, with the maintenance of IAP ≤15mmHg as the treatment goal. However, surgical decompression, including invasive drainage, should be considered in cases that are refractory to conservative treatment.

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Therapeutic intervention and surgery of acute pancreatitis in the 2010 guidelines have been dramatically revised into intervention for local complications in the 2015 guidelines, by incorporating the revised Atlanta classification and the confirmed evidence of step-up approach for necrotizing pancreatitis. The definition of local complications after acute pancreatitis and their approach have been extensively changed not only because the term "pancreatic abscess" had been discarded and instead a new concept of "walled-off necrosis" (WON) has been adopted, but also because the concept of step-up approach to local complications has been adopted in the 2015 Guidelines. Percutaneous drainage or endoscopic transluminal drainage should be first given regardless of the type of local complications when clinical symptoms and blood test findings deteriorate. If possible, therapeutic intervention should be performed after 4 weeks of onset, when the necrosis has been sufficiently walled off, that is, until the time of development of WON.

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The Japanese practice guidelines for the management of chronic pancreatitis were first published in 2009, and the second version was released in 2015. High-potency enteric-coated pancrelipase and elemental diet were newly highlighted in this revised guideline. High-potency enteric-coated pancrelipase has a weak recommendation in curing painful chronic pancreatitis (evidence level B), but has a strong recommendation for the treatment of steatorrhea with weight loss (evidence level A). Elemental diet is an option to treat patients with an attack or recurrent pain, after lifestyle education comprised of abstinence from smoking.

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In the Clinical Guideline for the Management of Chronic Pancreatitis 2015, extracorporeal shock wave lithotripsy (ESWL)/endoscopic therapy is highly recommended for treatment of painful uncomplicated chronic pancreatitis because of favorable long-term clinical outcomes from the recent published literature and ESWL has been covered by health insurance since 2014. Conventionally, pancreatic stenting is recommended for one year at the longest. Here, we describe the effectiveness, role and status of ESWL/endoscopic treatment modalities for the management of chronic pancreatitis. This Guideline will become more important since ESWL/endoscopic therapy is expected to be widely used in Japan due to its coverage by health insurance.

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Pancreatic diabetes mellitus (DM) is a type of secondary diabetes associated with exocrine pancreatic diseases such as chronic pancreatitis. Chronic pancreatitis generally results in the destruction and reduction of pancreatic endocrine and exocrine function. In patients with pancreatic DM frequently, this frequently leads to malnutrition resulting from maldigestion and malabsorption, as a result of insufficiencies in pancreatic digestive enzymes, and show unstable glycemic control and prolonged hypoglycemia stemming from insufficiencies in the synthesis and secretion of both insulin and glucagon. Intensive insulin therapy can be instituted in order to achieve stable glycemic control in patients with pancreatic DM. Recently, incretin-based therapy has been used for type 2 DM. However, at this point, there is insufficient evidence to support the safety and efficacy of incretin-based therapy for patients with DM secondary to chronic pancreatitis. Based on the recommendations of the Japanese guidelines for the management of chronic pancreatitis 2015, the use of incretin-based therapy for patients with DM secondary to chronic pancreatitis should only be considered when the benefits outweigh the risks.

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The recommendations concerning surgical therapy in Japanese guidelines revised in 2015 have been summarized as follows. Surgical therapy is recommended to be selected for the cases with intractable pain in which endoscopic therapy is neither effective nor possible. Concerning the selection of surgical procedures, in the cases with the dilated main pancreatic duct the pancreatic duct drainage operation such as side-to-side pancreaticojejunostomy should be selected, and pancreatectomy can be selected in the cases without pancreatic duct dilatation. In the cases with both the main pancreatic duct dilatation and the calcification in the pancreas head, Frey procedure rather than Beger procedure is recommended to be selected in Japan because the perioperative morbidity is less frequent in the Frey procedure, and because Beger procedure is not popular in Japan. In the clinical stage without pancreatic insufficiency (the compensated stage), the operation with pancreatic duct drainage may be beneficial for the maintenance of pancreatic function.

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Protease activated receptor-2 (PAR-2) is expressed in both the pancreatic duct cells and pancreatic acinar cells in the condition of pancreatic injury, promotes pancreatic secretion, and protects the pancreas by detoxification. In post-ERCP pancreatitis (PEP), the activation of trypsin induces PAR-2 activation for the protection of the pancreas. However, in the case with the obstruction of the duodenal papilla PAR-2 activation brings resultant ductal hypertension, and exacerbates pancreatitis. Thus, proper pancreatic duct drainage is reasonable approach for the prevention and protection from the aggravation of PEP.

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The patient was a male in his 60s who was referred to our hospital for further evaluation after dilatation of the main pancreatic duct and a high value of CA19-9. ERP revealed that the main pancreatic duct was disrupted in the pancreatic head, and the patient was diagnosed with adenocarcinoma by exfoliative cytology. The observation of vascular anatomy by abdominal CT showed hepatomesenteric type hepatic artery variation and occlusion at the root of the superior mesenteric artery. After further evaluation by angiography and 3D image analysis, we performed pancreaticoduodenectomy. By conserving collateral blood circulation as much as possible to secure vascular flow of the superior mesenteric artery and the hepatic perfusion, surgical resection was safely performed without reconstruction of the hepatic and mesenteric arteries. There are some reports on cases of resected pancreatic head tumors with stenosis or obstruction of the superior mesenteric artery. In the present case, however, hepatomesenteric type hepatic artery variation was involved. We found it essential to fully comprehend the hemodynamic status in order to ensure hepatic perfusion at the time of resection, and to maintain careful surgical maneuvers.

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Acinar cell carcinoma (ACC) of the pancreas is a rare tumor, accounting for 1% to 2% of primary pancreatic neoplasms. Because of its rarity and some histologic similarities to neuroendocrine tumors (NETs), it is generally difficult to establish the diagnosis based on small tissue samples such as needle biopsy. Herein, we report two cases of ACC, where the diagnosis was confirmed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) biopsy. Both patients were in their 70s. Tumors sizes were 95mm and 56mm, respectively. Both patients were found to have liver metastases at the initial presentation. EUS-FNA biopsy samples consisted of fragmented tumor tissue, where neoplastic cells were arranged in solid and acinar patterns. The cells have round enlarged nuclei and eosinophilic cytoplasm. Both cases were at least focally positive for both neuroendocrine (i.e., synaptophysin) and acinar markers (trypsin). BCL10, a recently identified immunohistochemical marker for ACC, appeared to be diffusely positive in the tumors, leading to the diagnosis of ACC. Given that BCL10 is a highly specific and sensitive marker for pancreatic ACCs, immunohistochemistry for this molecule will help us to diagnose this rare neoplasm by small tissue samples such as EUS-FNA biopsy.

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