Background: Although pembrolizumab was approved in Japan for the treatment of solid tumors with high-frequency microsatellite instability (MSI-H) which progressed after prior standard treatment in December 2018, there have been few reports of MSI-H pancreatic cancer in Japan because of its rarity. METHODS: We retrospectively examined 184 patients with unresectable pancreatic cancer (PC) who underwent MSI evaluation and the results of treatment using pembrolizumab for patients with MSI-H PC. Results: MSI-H was observed in 4 patients (2.2%), and pembrolizumab was administered to 3 patients. A partial response was achieved in 1 of 3 patients, which was a G-CSF-producing tumor. Conclusion: The frequency of MSI-H PC in our institution was 2.2%, consistent with previous reports. Since pembrolizumab treatment of patients with MSI-H PC could contribute to longer survival, MSI evaluation should be done proactively to increase the administration of promising treatment options.

A 78-year-old female presented with a tumor in the pancreatic head. A tumor in the uncinate process of the pancreas was visualized with strong contrast enhancement on computed tomography scan measuring 30mm, and diagnosed as a pancreatic neuroendocrine tumor by endoscopic ultrasound-fine needle aspiration biopsy. A pylorus preserving pancreaticoduodenectomy was performed. When the pancreatic head was dissected and transected above the portal vein, the pancreatic parenchyma was noted to be fused continuously with the pancreatic body on the left side of the portal vein, establishing the diagnosis of portal annular pancreas (PAP). The pancreas on the ventral side of the portal vein running through the main pancreatic duct was reconstructed with a conventional duct-to-mucosa pancreatico-jejunostomy and the dorsal side was divided using the linear stapler. The patient was discharged on postoperative day 17 without postoperative complications. We could not identify PAP on radiological re-evaluation. PAP is a very rare congenital anomaly, and it may be associated with an increased risk for development of a postoperative pancreatic fistula. In patients with PAP with a tumor located in the pancreatic uncinate process, it may be difficult to diagnose PAP preoperatively. The PAP anomaly must be kept in mind during pancreatic surgery.

A 40-year-old man underwent left nephrectomy for renal cell carcinoma 3 years previously. Chemotherapy for residual lung metastases was given postoperatively, but was interrupted by episodes of pancreatitis. Three mass lesions were found in the tail of the pancreas by CT scan. The masses were considered a local recurrence around the pancreas, causing pancreatitis. Distal pancreatectomy was planned to allow continuation of chemotherapy. Pathological examination revealed that the lesions around the pancreatic tail were consistent with local recurrence of renal cell carcinoma. The tumor advanced like an embolus into the main pancreatic duct with chronic inflammation in the caudal pancreas. Repeat episodes of pancreatitis were due to obstruction of the main pancreatic duct by recurrent tumor. Although renal cell carcinoma is known to progress into large vessels including the inferior vena cava, no pathological features such as the capsule formation seen with intra-vascular spread were found in the intra-pancreatic ductal lesion. Chemotherapy for residual lung metastases was resumed postoperatively and continued without further episodes of pancreatitis. Resection of recurrent renal cell carcinoma, even though it is incurable, may be justified to allow continued administration of effective chemotherapy.

A 25-year-old woman was incidentally noted to have a cystic lesion in the tail of the pancreas, and was referred for further evaluation. Abdominal contrast-enhanced CT and MRI scans showed a 5cm cystic mass in the tail of the pancreas, suggesting a mucinous cystic neoplasm (MCN), and the patient was followed. Follow-up was interrupted by pregnancy 7 years later, and the patient was re-examined 12 years after initial presentation. The cystic mass had increased to 6cm, was multiloculated, and associated with an elevated serum CA19-9 level. Laparoscopic distal pancreatectomy and splenectomy was performed. The postoperative course was unremarkable and she was discharged on postoperative day 11. Histopathological findings showed ovarian-like stroma, and the diagnosis was minimally invasive mucinous cystadenocarcinoma of the pancreas. To elucidate the natural history of MCN, it is necessary to evaluate patients with long-term follow-up.

A 33-year-old male presented with upper abdominal pain that persisted after the previous night's meal. He was diagnosed with acute pancreatitis by laboratory data and abdominal dynamic computed tomography scan. On admission, the serum triglyceride (TG) level was markedly elevated (6225mg/dl), suggesting acute pancreatitis with hypertriglyceridemia, which prompted transfer to our hospital for intensive care. He was treated with continuous regional arterial infusion for 5 days, and low-density lipoprotein (LDL) apheresis was performed on the day of transfer. After one session of LDL apheresis, the TG level decreased to 479mg/dl with improvements in the patient's clinical symptoms and serologic findings. On the 21st day of hospitalization, he was discharged without complications. LDL apheresis is preferred for patients with hypertriglyceridemia because of its safety and selectivity for lipids. In this report, decreasing the TG level via LDL apheresis in addition to standard procedures was effective in the treatment of a patient with acute pancreatitis with hypertriglyceridemia.

A 76-year-old female received adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic cancer 17 months previously. One year later, CT scan revealed peritoneal dissemination and Pembrolizumab was given. Five months later, she developed hyperglycemia and ketoacidosis, which required intensive management including insulin in the ICU. She was diagnosed with acute-onset type 1 diabetes mellitus and discharged on hospital day 24 without complications. This patient serves as an important reminder to consider adverse events including type 1 diabetes mellitus when giving anti-programmed cell death protein-1 antibody.

A 60-year-old man underwent subtotal gastric pancreaticoduodenectomy for distal bile duct carcinoma. The patient initially had a good clinical course without recurrence but presented with back pain and weight loss 66 months after resection, and a mass was observed in the remnant pancreas. Abdominal CT scan revealed a 30mm- mass with uneven contrast enhancement in the pancreatic tail. PET-CT also revealed abnormal accumulation in the same area. Total pancreatectomy was performed based on the diagnosis of remnant pancreatic cancer. Histopathological examination revealed one lesion that was adenosquamous cell carcinoma and two lesions that were invasive ductal carcinoma of the pancreas. We report a patient with synchronous pancreatic lesions with adenosquamous cell carcinoma and invasive ductal carcinoma in the remnant pancreas after resection of distal bile duct carcinoma.

A-65-year-old man with a mass in the body of the pancreas seen on ultrasonography was referred for further evaluation. Abdominal contrast-enhanced computed tomography scan revealed a 10mm enhancing lesion in the body of the pancreas along with stenosis of the main pancreatic duct stenosis near the lesion and caudal dilation. Although a pancreatic neuroendocrine tumor was suspected, we performed endoscopic ultrasonography-guided fine-needle aspiration because pancreatic ductal carcinoma could not be ruled out. Histopathological analysis revealed a PNET G1. Distal pancreatectomy was performed, and immunostaining was positive for chromogranin A, synaptophysin and serotonin. Fibrosis caused by serotonin was thought to be involved in the pathogenesis of the main pancreatic duct stenosis in this patient.

A 70-year-old man was admitted to a local hospital with acute pancreatitis. He was referred after MRI scan revealed a tumor in the pancreatic tail. Since PET-CT and cytologic evaluation of the pancreatic showed no malignancy, we followed up at short intervals considering it to be a benign tumor. There was almost no change in the tumor after six months. CT scan showed a slowly increased size with a concentration of FDG after one year. Pancreatic tail carcinoma was suspected and we performed a distal pancreatectomy and splenectomy with D2 dissection. Pathological examination showed pancreatic mucinous carcinoma (pT2N0M0 Stage IB).

The malignancy was difficult to diagnose in the presence of acute pancreatitis, negative tumor markers, negative multiple cytological examinations including FNA (fine needle aspiration) and SPACE (serial pancreatic juice aspiration cytological examination). We report difficulty in establishing the diagnosis of pancreatic mucinous carcinoma in a patient with acute pancreatitis.

A 68-year-old man presented with hydronephrosis. Computed tomography scan showed a tumor with invasion of the portal vein and splenic artery from the pancreatic head to the body. Histological examination of EUS-FNA specimens confirmed adenocarcinoma. The diagnosis was cStage IIA borderline resectable pancreatic carcinoma, cT3N0M0. He was treated with 2 courses of neoadjuvant chemotherapy (Gemcitabine plus Nab-paclitaxel (GnP) ). The primary tumor reduced in size by 21% after 2 courses of GnP which was no longer invading the portal vein or splenic artery. He then underwent pancreaticoduodenectomy with splenic artery resection (PD-SAR), because it was difficult to separate the tumor from the splenic artery. The pathological diagnosis was pStage IIB invasive ductal carcinoma (pT3, N1b (4/23), M0, TS1 (15mm), sci, INFc, ly1, v1, ne1, mpdX, pCH0, pDU0, pS1, pRP1, pPV1 (PVsp), pA0, pPLX, pPCMX, pBCM0, pDCM0 pDM0) and the therapeutic effect was grade1b. He received adjuvant chemotherapy using S1 but has a local recurrence 2 years after surgery, and was treated with GnP again after radiation therapy. Even in patients with invasion of the splenic artery requiring total pancreatectomy, PD-SAR may be a promising surgical strategy which maintains postoperative quality of life, residual pancreatic function and a radical resection.

Cystic pancreatic neuroendocrine tumors (PNET) are relatively rare. We report a patient with a purely cystic PNET. A 61-year-old woman presented with lower abdominal pain. Computed tomography (CT) scan showed a 30-mm cystic lesion with a well-defined, thin enhancing peripheral rim in the pancreatic head without a solid component. The slightly high density on CT scan and hyperintensity on magnetic resonance imaging with T2-weighted imaging showing a fluid-fluid level in the cystic lesion were consistent with a bloody component. Contrast-enhanced endoscopic ultrasound using Sonazoid^® revealed a 2-mm cyst wall with early enhancement. Following a diagnosis of cystic PNET, pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen showed a 32-mm cystic tumor with bloody content and a capsule. Immunohistochemical analysis revealed positive staining for chromogranin and synaptophysin. The Ki-67 index was <2%. The final diagnosis was nonfunctioning PNET grade 1.