Pancreatic endocrine and exocrine function is frequently impaired in pancreatic disorders, such as acute pancreatitis, chronic pancreatitis, autoimmune pancreatitis, pancreatic neoplasms, pancreatic resection, and cystic fibrosis. Management for pancreatic endocrine and exocrine function have been described in detail in the Japanese practice guidelines for chronic pancreatitis and autoimmune pancreatitis, whereas clinical questions regarding pancreatic function are not sufficient addressed in the domestic guidelines for acute pancreatitis, pancreatic neoplasms, pancreatic resection, or cystic fibrosis. In this article, we discuss these issues and review overseas practice guidelines from US, Italy, Australia, Spain, Romania, and IAP/APA.

Pancreatic diseases often complicate diabetes mellitus and malabsorption caused by pancreatic endocrine and exocrine dysfunction. Diabetes mellitus complicated with pancreatic diseases is termed "pancreatic diabetes mellitus". It is caused by pancreatic exocrine and endocrine dysfunction. On treatment of pancreatic endocrine dysfunction, examinations of diabetes and insulin secretion are required. There are six kinds of examinations of insulin secretion; insulinogenic index (II), HOMA-B, serum C-peptide, 24-hour urinary C-peptide, C-peptide index (CPI), secretory unit of islet transplantation (SUIT), glucagon stimulation test. Insulin therapy is required for the patients with insulin dependence. In the case of insulin therapy for pancreatic diabetes mellitus, sufficient caloric intakes, pancreatic enzyme replacement therapy, and adjustment of insulin preparation are necessary to avoid hypoglycemia.

In order to investigate the usefulness of organ preserving pancreatectomy, fat absorption was studied using the stable isotope ¹³C-Trioctanoin breath test for each pancreatic head resection. For the analysis, "Aa", which is an indicator of digestion and absorption ability not affected by gastric emptying rate, was calculated using the Wagner-Nelson method. There was no significant difference between volunteers and duodenum-preserving pancreatic head resection (DPPHR).

When comparing volunteers and pylorus-preserving pancreaticoduodenectomy (PPPD), absorption was significantly reduced in both, subtotal stomach-preserving pancreaticoduodenectomy (SSPPD), and pancreaticoduodenectomy (PD). DPPHR showed significantly better absorption than PD, PPPD and SSPPD. Comparison of absorption before and after surgery showed no difference between DPPHR before and after surgery, but PD, PPPD and SSPPD showed significantly lower absorption after surgery. The ¹³C-Trioctanoin breath test is a pancreatic exocrine function test which can be evaluated simply and noninvasively in real time. Organ preserving pancreatectomy is a useful technique for obtaining a good pancreatic exocrine function after surgery.

Enzyme therapy for patients with exocrine pancreatic insufficiency has been studied a wide variety of conditions, such as enzyme activity, acid tolerance or mixing with foods, though the concept of "replacement for the loss of pancreatic function" is very simple. Recent findings provide robust clinical evidence supporting the usefulness of the replacement therapy using a high dose of enzyme and high activity enzyme to form a consensus that this therapy contributes greatly to the patient's QOL. But some patients do not achieve satisfactory therapeutic effects due to methodological mistakes of taking enzyme or patient misselection.

CFTR anion channel mediates Cl^- and HCO₃^- transport in various epithelia. Loss of function due to severe mutations in both alleles of the CFTR gene causes thick and acidic mucus in the lumen and multiple organ diseases. Typically, in cases of cystic fibrosis, meconium ileus develops just after birth, respiratory infection occurs repeatedly afterwards, and pancreatic insufficiency is established by ~2 years of age, leading to nutritional failure and poor growth. Abdominal CT images reveal fatty replacement or atrophy of pancreas in most of the patients. Although the quality of life and prognosis are largely defined by the severity of pulmonary disease, poor nutritional state and lung function are inversely correlated. Thus, pancreatic exocrine function should be evaluated and pancreatic enzyme replacement therapy should be started as early as possible. Measurement of fecal elastase accurately and easily distinguishes the presence or absence of pancreatic insufficiency. Since there is substantial exhaustion due to chronic lung infection, and severe and persistent cough, patients require a greater energy intake in combination with acid-resistant enteric coating preparations of enzymes.

We report the results of pancreatic endocrine and exocrine function of patients who underwent pancreatic resection and discuss the preservation of pancreatic endocrine and exocrine function after pancreatic resection. Pancreatic endocrine and exocrine insufficiency occurred in 41.0% and 65.5% of patients who underwent pancreatoduodenectomy and 30.8% and 26.4% of patients who underwent distal pancreatectomy, respectively. Remnant pancreatic volume after pancreatic resection was the only independent risk factor of pancreatic endocrine insufficiency as well as pancreatic exocrine insufficiency. Stenosis or obstruction of pancreaticoenteric anastomosis induces postoperative atrophy of remnant pancreas. Reliable pancreaticoenteric anastomosis is important to prevent postoperative pancreatic endocrine and exocrine insufficiency. Moreover, adequate administration of pancreatic enzyme supplements or insulin is mandatory for patients who develop postoperative pancreatic endocrine and exocrine insufficiency after pancreatic resection.

We performed a nationwide survey of prevailing practices in management of pancreatolithiasis. We collected clinical data from 1834 patients treated for pancreatolithiasis at 125 hospitals. Patients included 1479 men and 355 women. ESWL alone was performed in 103 patients (5.6%); ESWL plus an adjunctive endoscopic procedure in 446 (24.3%); endoscopic treatment alone in 261 (14.2%); and surgery in 167 (9.1%). Other therapies were given to 358 (19.5%) patients. No treatment was considered in 499 (27.2%). Symptom relief rate was 85.7% after ESWL including adjunctive endoscopic treatment, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL including adjunctive endoscopic treatment, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Rates of late complications after ESWL including adjunctive endoscopic treatment, endoscopic procedures alone and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief rates, but also early and late complication rates, for surgery were significantly higher than for ESWL and endoscopic treatment. Among 417 patients treated with ESWL, 61 (14.6%) required surgery, as did 32 (16.0%) of 200 patients treated endoscopically. Re-operation was required in 11 (6.7%) of 164 patients who were treated with surgery. The need for operation was significantly less frequent after surgery than that for surgery after the other treatments. In Japan, non-surgical treatments were chosen more frequently than surgical treatment for patients with pancreatolithiasis. The first-line treatment of pancreatolithiasis might be ESWL alone or with endoscopy because of minimal invasiveness and low incidence of early complications. Appropriate guidelines for clinical management of pancreatolithiasis should improve efficacy and safety.

A 74-year-old man with jaundice was referred to us to further evaluation of a pancreatic head lesion. Dynamic computed tomography and endoscopic ultrasonography revealed a 50-mm tumor with central necrosis localized in the head of the pancreas. The tumor had peripheral enhancement in enhanced CT and enhanced EUS images. As the tumor was suspected to be a neuroendocrine tumor with cystic degeneration on imaging, the patient underwent pancreaticoduodenectomy. Histological examination revealed that the tumor consisted of atypical epithelium arranged in a complex papillary architecture. Tumor cells were positive for MUC1, MUC5AC, MUC6 and were negative for MUC2 on immunohistochemistry. These findings led to the diagnosis of pancreatobiliary-type intraductal papillary mucinous carcinoma. We have reported a case of pancreatobiliary-type intraductal papillary mucinous carcinoma mimicking a neuroendocrine tumor.

A 75-year-old woman presented with complaints of epigastric pain and an abdominal CT scan revealed a 2.5cm mass located in the pancreatic body. We diagnosed it as pancreatic cancer by endoscopic ultrasonography-guided fine-needle aspiration with neuroplexus invasion around splenic and celiac artery. After two courses of gemcitabine plus nab-paclitaxel neoadjuvant therapy, we performed distal pancreatectomy with celiac artery resection. Pathological examination of the resected tissue revealed adenosquamous carcinoma surrounded by type 1 autoimmune pancreatitis characterized by infiltration of IgG4-positive plasma cells and obliterative venulitis. We encountered a rare case of adenosquamous carcinoma associated with type 1 autoimmune pancreatitis. We review cases of pancreatic cancer associated with autoimmune pancreatitis reported in the literature.

A 65-year-old female underwent distal pancreatectomy with splenectomy for IPMC in the pancreatic tail in 2001 and a partial resection of uncinate process for IPMC in 2002. During the next 10 years, MPD dilation aggrandized to approximately 14mm in diameter and multilocular cysts in pancreas increased. We diagnosed as a recurrent IPMC in the remnant pancreas, in spite of a histopathological analysis that did not a reveal a malignancy. Complete pancreaticoduodenectomy and D2 Lymph node dissection and PLce, PLsma dissection were performed. Remnant tissue diagnosis revealed IPMC in MPD near the papilla vater, which was distant from the surgical margin of previous surgeries. This was determined to be a new lesion that was different from previous IPMC. Surgery should be considered for cases in which MPD dilatation and multilocular cysts increase in the remnant pancreas in order to improve patient prognosis.

We report a rare case of pancreatic cancer, mixed adeno-neuroendocrine carcinoma. A 47-year-old man was admitted to our hospital because of jaundice. Abdominal enhanced computed tomography showed an unclear demarcated mass 36mm in the head of the pancreas. ERCP showed a stenosis in main pancreatic duct and distal bile duct. On FDG/PET-CT, the tumor showed high SUVmax=3.9. With a diagnosis of pancreatic carcinoma, the patient underwent a pylorus preserving pancreatoduodenectomy. Histological and immunohistochemical examinations revealed that the tumor consisted of ductal component and neuroendocrine component. By these findings, the tumor was diagnosed as mixed ductal-neuroendocrine carcinoma. The patient received biweekly gemcitabine and S-1 chemotherapy for 20 months as adjuvant chemotherapy. Twenty-one months after the surgery, CT revealed multiple liver metastases. The patient received gemcitabine and S-1 chemotherapy for metastatic disease. Thirty months after the surgery, the patient underwent liver biopsy. Histological and immunohistochemical examinations of the liver specimen showed that the tumor consisted of neuroendocrine tumor without ductal carcinoma component. The patient was treated with 10mg of everolimus orally as a treatment for the neuroendocrine tumor. Seven years and 3 months after the surgery, the patient is still undergoing treatment.

Pancreatic arteriovenous malformation (PAVM) associated with acute pancreatitis is very rare disease. A 45-year-old man presenting with upper abdominal pain was diagnosed with mild acute pancreatitis. We observed PAVM in the pancreatic body and tail. Acute pancreatitis is considered to be caused by PAVM, therefore a distal pancreatectomy was performed. Histopathological examination revealed PAVM and focal chronic pancreatitis around the lesion of PAVM. We considered that acute pancreatitis is mainly caused by the steal phenomenon due to PAVM.

A 52-year-old woman with a ruptured pancreatic cystic tumor was referred to our hospital. Abdominal CT scan revealed a 10cm cystic tumor with intratumoral hemorrhage at the distal pancreas and bloody ascites around the tumor and right side of the liver. MRI showed "cyst in cyst" findings in the pancreatic cystic tumor. A multilocular cystic tumor with abundant coagulum in the distal pancreas was observed by endoscopic ultrasonography. A mucinous cystic neoplasm (MCN) with spontaneous rupture was suspected. Hemorrhage from the tumor was stopped by conservative treatment. A distal pancreatectomy was performed two months after the onset. Histological findings revealed a cystic wall with ovarian-like stroma. Thus, the tumor was pathologically diagnosed as mucinous cystic adenoma. In Japan, only 8 cases of ruptured MCN have been reported. Here we report a rare case of MCN with spontaneous rupture and review previous case reports of ruptured MCN in Japan.

A 42-year-old woman visited our hospital because of jaundice, and was diagnosed as pancreatic head cancer with multiple liver metastases. After 16 courses of 1^st line chemotherapy (mFOLFIRINOX), the size of the pancreatic cancer and liver metastases increased on CT. Twelve months after 2^nd line chemotherapy (GEM+nab-PTX), the pancreatic tumor and liver metastases were undetectable except for one liver metastatic lesion. Staging laparoscopy and excisional liver biopsy were performed. Histopathological examination revealed no cancer cells in the liver. Thus, we performed a pancreaticoduodenectomy. Histopathological examination revealed no viable tumor cells in the pancreas. The postoperative course was uneventful, and the patient is still alive without recurrence for twelve months after surgery.