Approximately 60% of pancreatic cancers occur in the pancreatic head and may present with obstructive jaundice due to bile duct invasion. Obstructive jaundice often leads to poor general condition and acute cholangitis that can interfere with surgery and chemotherapy and require biliary drainage. The first choice for bile duct drainage in both resectable and unresectable cancers is the endoscopic transpapillary approach. However, in cases when this approach is difficult or impossible, endoscopic ultrasound-guided biliary drainage (EUS-BD) has reported favorable outcomes. This article describes the current state and recent trends of biliary drainage in the treatment of distal bile duct obstruction due to pancreatic cancer.

Endoscopic pancreatic duct drainage has been by transpapillary or trans-anastomotic approach, and more recently by transluminal approach. In a transpapillary approach, a pancreatic stent or nasopancreatic drainage tube is inserted through the papilla after pancreatography and guidewire insertion to the pancreatic duct using duodenoscope or balloon-assisted enteroscope. Transpapillary/anastomotic pancreatic drainage is employed frequently for impaired pancreatic drainage such as chronic pancreatitis. In addition, the preventive effect of pancreatic stents for patients with post-ERCP pancreatitis has been widely accepted. Transluminal pancreatic drainage has been regarded as an alternative approach for transpapillary drainage. A plastic stent is inserted through the gastric wall to the pancreatic duct after puncture of the pancreatic duct under endoscopic ultrasound (EUS), guidewire insertion to the pancreatic duct, and dilatation of the puncture site. A transpapillary or trans-anastomotic approach should consider a rendezvous technique in cases of difficult dilatation of the puncture site. However, given technical success and high complication rates, transluminal pancreatic drainage should be limited to endoscopists proficient in EUS-related procedures.

Because of its efficacy, safety, and minimally invasive nature, several guidelines regard endoscopic treatment combined with extracorporeal shock wave lithotripsy (ESWL) as first-line treatment for symptomatic patients with pancreatic duct stones. Small floating stones in the main pancreatic duct can be treated by endoscopic pancreatic stenting, endoscopic nasopancreatic drainage, endosco-pic pancreatic sphincterotomy, and endoscopic stone removal alone, but in most cases endoscopic treatments are combined with ESWL as appropriate. However, since endoscopic removal of pancreatic stones is technically difficult, it should be performed by an experienced pancreatobiliary endoscopist. In addition, since surgical treatment is superior to endoscopic treatments in long-term prognosis, it should be considered when ESWL and endoscopic treatments are believed to be inappropriate and ineffective.

The endoscopic approach to pancreatobiliary disease with postoperative intestinal reconstruction has become practical with balloon-assisted enteroscopy (BAE). BAE interventions are considered first-line treatment for biliary disease, yet it is difficult for pancreatic diseases (especially pancreatic jejunal anastomosis), so mainly EUS interventions are reported. Recently, new double balloon enteroscopy (DBE) and single balloon enteroscopy (SBE) treatments have been reported.

This article reviews DBE treatment of pancreatic diseases, especially pancreaticoje-junal anastomotic stenosis in postoperative cases with reconstructed anatomy.

Most symptoms of pancreatic fluid collection (PFC), a typical late complication associated with acute pancreatitis, are an indication for drainage. Recently, endoscopic ultrasonography-guided transluminal drainage (EUS-TD) has been used widely and favorable outcomes reported. Technological progress in this field has been remarkable such as specialized metal stents for improved drainage. However, walled-off necrosis (WON) for large amounts of encapsulated necrotic tissue is often difficult to treat with EUS-TD alone due to poor drainage, so the "step-up approach" with direct endoscopic necrosectomy (DEN) in steps has become the mainstay treatment. Although therapeutic efficacy of EUS-TD and DEN for difficult-to-treat PFC has increased over the years, fatal adverse events can sometimes occur. Familiarity with treatment indications, technique, and plans for possible complications are important.

The first endoscopic ultrasound (EUS)-guided ablation therapy for symptom palliation of pancreatic neuroendocrine neoplasms (PNENs) was ethanol injection for insulinomas performed in patients with impaired tolerance for surgery, resulting in improved hypoglycemic symptoms. Subsequent several case reports have reported the usefulness of EUS-guided ethanol injection therapy (EUS-EIT) for symptom palliation with insulinoma smaller than 15mm. However, complete ablation rate of EUS-EIT for non-functional PNENs is not high, less than 80%. The complete ablation rate of EUS-guided radiofrequency ablation (EUS-RFA) is higher, but the rate of serious complications is believed higher compared with EUS-EIT. Furthermore, the necessity of aggressive treatment for low-grade PNENs <10mm is still controversial. In addition to accumulating evidence, long-term prognosis requires examination to determine the size of PNEN indicated and whether ethanol injection therapy or radiofrequency ablation is the best treatment.

EUS-guided ablation (EUS-Ab) for pancreatic cystic neoplasms (PCN) is indicated for cysts at least 2 to 6cm in diameter for patients who are inoperable or who have refused surgery with reasonable life expectancy. EUS-Ab can be fine needle aspiration (EUS-FNA) injection of ethanol or anticancer drugs into the cyst, or by radiofrequency ablation using thermal energy to kill tumor cells. Reported rates of cyst lumen obliteration vary, but despite some efficacy long-term outcomes are still unclear. Overall, EUS-guided treatment has great potential, and merits greater development and usage in Japan.

Endoscopic ultrasound (EUS)-guided antitumor therapy, the new frontier in pancreatic cancer management, roughly divides into ① tumor ablation therapy and ② intratumoral local injection therapy. The first uses ethanol ablation, photodynamic therapy (PDT), radiofrequency ablation (RFA), cryocoagulation, and brachytherapy; the second uses injection of molecular biologic mechanisms. Studies of anticancer agents, adenoviral vectors, DNA plasmids, allogeneic mixed activated lymphocytes, dendritic cells, and nucleic acid drugs have also been published, including about EUS-guided fiducial marker placement. Following a review of these methods, results of clinical trials of EUS-guided fine needle injection of STNM01, the RNA oligonucleotide targeting carbohydrate sulfotransferase 15, are reported.

Endoscopic Ultrasound-guided Celiac Plexus Neurolysis (EUS-CPN) is a non-pharmacologic treatment for cancer pain and an optional measure when adequate control with pharmacologic therapy is difficult. EUS-CPN techniques include the central method (CI) in which puncture and injection are performed at the origin of the celiac artery, the bilateral injection (BI) method approaching both sides of the celiac artery, and celiac ganglia neurolysis (CGN) in which puncture and injection are performed directly in the celiac ganglia. Clinical studies and meta-analyses have supported the safety, pain relief, opioid reduction, and quality of life benefits of all three techniques. However, the optimal choice of technique remains debated and should be evaluated in well-designed randomized controlled trials. Recently, radiofrequency ablation (EUS-RFA) and radioactive seed implantation in the celiac ganglia have been reported as an extension of EUS-CPN. These new techniques have been reported only in a few cases, so more extensive studies are needed in future.

Duodenal stenting is a widely used endoscopic treatment for malignant gastric outlet obstruction (GOO). Compared to surgical gastrojejunal anastomosis, it has good short-term outcomes, fewer complications, shorter time to oral intake, and rapid initiation of chemotherapy. While anastomosis should be considered for long-term prognoses, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) can be a new minimally invasive endoscopic treatment for benign or malignant GOO, especially for terminal-stage patients. It is indicated for cases in which distance between stomach and jejunum, the target of the puncture, is close with no puncture site tumor invasion. According to recent reports, outcomes of duodenal stenting and EUS-GE are similar, but EUS-GE has lower re-intervention rates, shorter times to oral intake, shorter hospital stays, and fewer complications. EUS-GE has potential to become the future standard treatment approach for GOO, and further technological development and clinical trials for insurance coverage are expected.

Patient 1 was a 64-year-old woman who underwent evaluation due to weight loss. A 42mm diameter cystic lesion was found in the tail of the pancreas, and a 2mm-thick rim was enhanced in a contrast-enhanced CT scan arterial phase. In the resected specimen, the tumor was covered with a fibrous capsule, and there were no nodules, necrosis, or blood pooling within the cyst. A neuroendocrine tumor (NET) G1 was found inside the capsule, characteristic of so-called "purely cystic pancreatic neuroendocrine neoplasm (PNEN)". Patient 2 was an 80-year-old man who underwent evaluation for worsening diabetes. There was a 2mm diameter cyst in the tail of the pancreas, which was high-intensity on diffusion-weighted MRI and a 1-2mm-thick rim was enhanced by contrast-enhanced EUS (CE-EUS). The resected specimen showed a 5mm diameter cystic tumor with NET G1 proliferation on the inner surface of the fibrous capsule. These findings had the same histological structure as Patient 1. In Patient 2, CE-EUS observation was diagnostically useful, and EUS may have provided visualization of a very early purely cystic PNEN.

A 48-year-old woman with abdominal pain presented for a detailed examination because abdominal ultrasonography revealed a mass in the head of the pancreas. Contrast-enhanced CT scan showed a 15mm solid mass with delayed enhancement on the ventral side of the pancreatic head and T2-weighted MRI showed a high intensity mass. EUS showed a 15mm hypoechoic well-circumscribed mass in the pancreatic head. Based on these imaging findings, a pancreatic tumor was suspected, possibly a neuroendocrine tumor or solid pseudopapillary tumor, but further diagnosis was difficult. Therefore, EUS-FNB was performed and histopathology showed proliferated spindle cells arranged in fascicles with positive for protein S-100 on immunohistostaining, consistent with a pancreatic Schwannoma. With the history of abdominal pain, a decision was made to proceed with surgery and laparoscopic enucleation successfully performed. Final histopathological evaluation showed a pancreatic Schwannoma without malignancy. She was discharged on postoperative day 12 without complications and has no abdominal pain or recurrence 1 year postoperatively.

A 73-year-old woman presenting with liver dysfunction and dilatation of the common bile duct and intrahepatic bile ducts was referred for further examination and treatment. Imaging revealed a mass protruding into the pancreaticoduodenal groove, and endoscopic retrograde cholangiopancreatography with biliary brush cytology yielded Class V [malignancy] findings. Levels of tumor markers were also high, and the patient was diagnosed with pancreatic groove cancer. After preoperative chemotherapy, a pylorus-sparing pancreaticoduodenectomy was performed, and pancreatic groove cancer was definitively identified based on pathological examination. Here, 20 cases of pancreatic groove cancer reported in Japan are reviewed including the above case, to examine methods of preoperative diagnosis, pathological features, and prognosis. Pathologically, all cases displayed duodenal invasion, and common bile duct invasion was noted in 55.6% of cases. Duodenal mucosal biopsy, biliary pathology, and ultrasound endoscopy are helpful in preoperative diagnosis, but depending on imaging and endoscopic findings, multiple methods of diagnosis need be considered. In addition, the prognosis for patients with pancreatic groove cancer suggests possible benefits from combined-modality therapy as with typical pancreatic ductal carcinoma.