In 2015, the Japanese Society for Neuroendocrine Tumors (JNETS) published the first clinical practice guidelines for pancreatic and gastrointestinal neuroendocrine neoplasms (NEN) to standardize diagnosis and treatment. NEN is a rare tumor that develops in all organs and presents with various clinical symptoms. Pathological classification is ultimately important for the diagnosis of NEN, and it is necessary to select drug treatment strategies based on the pathological diagnosis. The second edition of revised guidelines was published in 2019 to reflect new trends, including WHO classification revision, the advent of somatostatin receptor scintigraphy, the addition of target diseases for molecularly targeted drugs and the somatostatin analogue lanreotide, and reexamination of surgical indications for non-functional pancreatic NEN. Peptide receptor radionuclide therapy (PRRT) has also emerged. In this article, we review the current status and future prospects of pancreatic NEN management.

Imaging of pancreatic neuroendocrine neoplasms (pNEN) is for ① tumor detection, ② differential diagnosis, ③ tumor staging, ④ evaluation of treatment response, and ⑤ evaluation of recurrence. However, if the tumor is not detected, evaluation of ② to ⑤ cannot be performed. Detection of tumors, pancreatic cancer and pNEN with US, CT or MRI can be difficult. Insulinomas in particular are often smaller than 1cm in diameter. For small tumors, endoscopic ultrasonography (EUS) is useful because of its superior spatial resolution. This article describes the imaging findings of pNEN for each imaging modality including tips on how to detect pNEN using EUS.

Radiopharmaceuticals consisting of radionuclides and somatostatin analogues for imaging and therapy are essential for theranostics. As imaging plays a major role in managing pancreatic and other neuroendocrine neoplasms (NEN), somatostatin receptor imaging and peptide receptor radionuclide therapy (PRRT) using somatostatin analogues with high tumor affinity has become indispensable for treatment. PRRT is safe, effective and can be used to treat NEN in any primary organ. Currently, it is positioned as a second-line treatment or later, but further studies can investigate its use as a first-line treatment and beyond four-dose protocols.

In pancreatic neuroendocrine neoplasms (NENs) classification, neuroendocrine tumors (NET G1-3) and neuroendocrine carcinomas (NEC) appear to be on the same spectrum, but their histogenesis and molecular biological behavior are radically different, which affects treatment strategies. Therefore, it is necessary to recognize them as completely different pathological entities and conduct appropriate pathological diagnoses. For cases when differential diagnosis is difficult using ordinary diagnostic methods, it is desirable that the pathologist establishes a communicative relationship with clinicians that allows for consideration of pathological, clinical prognostic, and treatment-related factors.

Systemic therapy for pancreatic NEN differs for pancreatic neuroendocrine tumor (NET) and pancreatic neuroendocrine carcinoma (NEC). For pancreatic NETs, treatment purpose differs between hormonal symptom control or tumor growth suppression. Somatostatin analogues are mainly for hormonal symptom control. Somatostatin analogues, molecular target agents, and cytotoxic agents are for tumor growth suppression. Proper use is guided by the treatment selection MAP for pancreatic NETs. In addition, radionuclide-labeled peptide therapy is now available in Japan, and timing of introduction is also important. Platinum-based chemotherapy is standard treatment for pancreatic NEC. Various treatments are available for pancreatic NEN, so a multidisciplinary approach that makes proper use of these treatments is required.

Tumors originating in the islet cells are also known as pancreatic neuroendocrine neoplasms (pNENs), and tumors are classified into well-differentiated NET and poorly-differentiated NEC. Functional tumors produce excess hormones that can lead to clinical syndromes, but the majority of pNENs are not associated with elevated hormone levels nor cause clinical syndromes, and are termed "non-functional". New drugs and treatments such as PRRT have been approved for pNENs in recent years, and options are expanding. However, pNENs have high malignant potential, and when possible radical resection is indicated as for other gastrointestinal cancers. Regarding treatment strategy for small, non-functioning pNETs that are diagnosed incidentally, some guidelines conditionally recommend observation, but caution is advised.

Few cases have been reported about surgery for pancreatic metastases, and cases from osteosarcoma are extremely rare. We report a case of pancreatectomy for metachronous pancreatic metastasis post-surgery for osteosarcoma. Surgery was performed on a 55-year-old man for osteosarcoma of the mandible 26 years ago. He received pulmonary resection, radiofrequency ablation, chemotherapy and radiation therapy for pulmonary metastases 2 years and 17 years after resection of primary tumor respectively. He was referred to our hospital with a pancreatic tumor from routine screening 7 years later. The mass measuring 53mm in size with blood flow in the tail of the pancreas was identified by CT. Endoscopic ultrasound (EUS) revealed the irregular mass with both low and iso echoic components, and the biopsy was compatible for metastatic osteosarcoma. PET-CT indicated an abnormal uptake value in the pancreatic tumor, but no evidence of other distant metastasis. He was diagnosed with metachronous pancreatic metastasis from osteosarcoma and distal pancreatectomy was performed. The post-operative course was good and he was discharged 10 days post-surgery with no complication. The pancreatic metastasis from osteosarcoma is extremely rare and this case is worth reporting because it is a rare pathology with recurrence after long-term follow-up.

A 38-year-old man was admitted to our hospital presenting with an emergency case of severe alcoholic acute pancreatitis with complaints of abdominal pain and vomiting after alcohol intake. He underwent consecutive successful treatments for acute pancreatitis, but one month after admission a CT scan showed an abscess around the pancreatic tail extending to the retroperitoneum. A transgastric stent was placed into the abscess, followed-up by a transgastric endoscopic necrosectomy. Because the abscess cavity was large and frequent endoscopic necrosectomies were not effective, we performed a laparoscopic necrosectomy and drain placement using a retroperitoneal approach by inserting a laparoscopic port directly into the abscess cavity under CT guidance in the hybrid operating room. The abscess cavity shrank, and the patient was discharged on the 78th day post-surgery with a drain in place. Since laparoscopic necrosectomy is useful in the treatment of massive walled-off necrosis caused by severe acute pancreatitis, we report the results of this procedure with some innovations implemented in our department.

An 85-year-old man underwent a pancreaticoduodenectomy (PD) for moderately differentiated tubular adenocarcinoma and had been followed recurrence-free without adjuvant chemotherapy. Three years and 10 months after the operation, he was referred to us with the chief complaints of epigastric pain. A blood test showed increased inflammatory reaction, and enhanced abdominal computed tomography revealed multilocular effusion in the remnant pancreas. A lost stent placed at the pancreaticojejunostomy was found to remain in the pancreatic duct, and we thus diagnosed a pancreatic abscess caused by its obstruction. The abscess was in close contact with the posterior wall of the stomach, and trans-gastric drainage was performed using endoscopic ultrasonography. The inflammatory findings and symptoms were immediately improved after drainage and the abscess cavity was significantly reduced. The lost stent spontaneously fell off and no recurrence of symptoms has been observed since. To the best of our knowledge, this is the first report of pancreatic abscess after PD with obstruction of a lost stent tube treated by endoscopic trans-gastric drainage.