Kenjiro Yamamoto

Elevated polyamines in saliva of pancreatic cancer

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data show the potential of saliva as a source for tests screening for PC.

Afferent loop syndrome treated by endoscopic ultrasound-guided gastrojejunostomy, using a lumen-apposing metal stent with an electrocautery-enhanced delivery system

Afferent loop syndrome is a complication that infrequently occurs after pancreaticoduodenectomy [1]. Complete obstruction occurs which leads to cholangitis, pancreatitis, perforation, and necrosis. In particular, patients with cancer recurrence cannot continue chemotherapy treatment, become debilitated, and may eventually die. Therefore, early and appropriate decompression treatment is needed. This report describes endoscopic ultrasound (EUS)-guided gastrojejunostomy for treatment of afferent loop syndrome, using a lumen-apposing metal stent (LAMS) incorporated into an electrocautery-enhanced delivery system. A 44-year-old man was admitted to our hospital with vomiting and abdominal pain; he had undergone pancreatoduodenostomy for pancreatic head cancer 11 months earlier. Computed tomography (CT) revealed dilation of the afferent loop associated with a recurrence of cancer (▶Fig. 1). First, multiple plastic stents were inserted by balloon-assisted enteroscopy (▶Fig. 2) and his clinical condition improved. However, 1 month later he was admitted again with abdominal pain because of stent occlusion. CT revealed dilation of the afferent loop and intrahepatic bile duct (▶Fig. 3). We performed EUS-guided gastrojejunostomy with a LAMS incorporated into an electrocautery-enhanced delivery system (Hot AXIOS; Boston Scientific, Natick, Massachusetts, USA) (▶Fig. 4, ▶Video1). CT on the following day showed improvement in the dilation of the afferent loop (▶Fig. 5). The patient showed resolution of clinical symptoms and received outpatient chemotherapy. A previous report has demonstrated the usefulness of LAMS for transenteric drainage of pancreatic pseudocysts and the gallbladder [2]. Recently, EUS-guided transgastric access into the afferent limb with LAMS has been reported [3, 4]. The use of the Hot AXIOS system has some advantages compared with conventional LAMS, namely, avoidance of the need to exchange devices for stent placement, shortening of procedure time, prevention of leakage in the abdominal cavity, and prevention of separation of the digestive wall and afferent loop tract wall during the procedure. Therefore, EUS-guided drainage with LAMS is a safe, easy-to-perform, and highly effective minimally invasive treatment modality for afferent loop syndrome.

A retrospective histological comparison of EUS-guided fine-needle biopsy using a novel franseen needle and a conventional end-cut type needle

Background and Objectives: Recently, a 22G Franseen needle for EUS-guided fine-needle biopsy (EUS-FNB) with three novel symmetric heels has been developed to adequately obtain a core tissue. Methods: All 38 consecutive patients with pancreatic masses who underwent EUS-FNB using a Franseen needle were investigated retrospectively to assess the efficacy and safety of EUS-FNB using the Franseen needle. Then, the EUS-FNB outcomes and histological assessments of the tissue obtained by EUS-FNB using the Franseen needle and EUS-FNA using the conventional end-cut type needle for each of the 30 pancreatic ductal adenocarcinoma cases were compared. Results: An accurate histological diagnosis of the Franseen needle was achieved with a mean of 2 passes in 97.4% of patients. Although the accurate histological diagnosis rate of pancreatic ductal adenocarcinoma was not significantly different (96.7% vs. 93.3%, P = 0.55), the mean number of passes in the Franseen needle was significantly less than that in the conventional needle (2.1 ± 0.4 vs. 3.2 ± 0.8, P < 0.001). The presence of desmoplastic fibrosis with neoplastic cellular elements and venous invasion were significantly higher (96.7% vs. 40.0%, P < 0.001 and 23.3% vs. 0%, P < 0.01, respectively) and the amount of obtained tissue was significantly larger with the Franseen needle (2.13 mm2 vs. 0.45 mm2, P < 0.001). Conclusions: EUS-FNB using the Franseen needle enables the acquisition of a larger amount of tissue sample and achieves an accurate histological diagnosis with a smaller number of passes than the conventional end-cut type needle.

Novel technique using a non‐tip and short‐wire papillotome for biliary cannulation of intradiverticular papilla in patients with Roux‐en‐Y anastomosis

BALLOON ENTEROSCOPY‐ASSISTED ENDOSCOPIC retrograde cholangiopancreatography (BEERCP) has enabled endoscopic treatment of pancreatobiliary disease in patients with surgically altered gastrointestinal anatomy. However, even though the endoscope can reach the papilla, successful cannulation of the common bile duct may be difficult in a papilla located within a diverticulum because of an insufficient distance from the papilla in the tangential direction. Therefore, endoscopic ultrasoundguided biliary drainage has been reported as a useful and safe method. Herein, we report BE-ERCP using a papillotome for cannulation of the intradiverticular papilla in R-Y anastomosis patients with choledocholithiasis. An 84-year-old woman who had undergone total gastrectomy with R-Yanastomosis for gastric cancer was admitted to our hospital for treatment of a choledocholithiasis. Abdominal computed tomography showed a stone in the common bile duct (Fig. 1). A short-type single-balloon enteroscope (SIF-H290; Olympus Medical Systems, Tokyo, Japan) was inserted into Vater’s papilla (Fig. 2). The papilla was inside the diverticulum,making it difficult to viewdirectly.Althoughweattempted to cannulate the common bile duct using a sphincterotome, we could not place the sphincterotome tip at the papillary orifice. Thereafter, we carried out cannulation using a papillotome (Cook Medical, Winston-Salem, NC, USA) which has no catheter tip and has a bow-up function of 90° (Fig. 3; Video S1). Initially, the papillotome was inserted into the ampullary orifice at the 12 o’clock direction and contrast medium was injected successfully into the common bile duct under fluoroscopic guidance. Cholangiogram showed diffuse dilation and a 13-mm stone filling defect in the common bile duct (Fig. 4). Then, a guidewire was advanced into the

Evaluation of novel slim biopsy forceps for diagnosis of biliary strictures: Single-institutional study of consecutive 360 cases (with video)

AIM To evaluate the feasibility and reliability of endoscopic transpapillary bile duct biopsy for the diagnosis of biliary strictures. METHODS A total of 360 patients (241 men) who underwent endoscopic retrograde cholangiopancreatography for biliary strictures with biopsy from April 2012 to March 2016 at Tokyo Medical University Hospital were retrospectively reviewed. This study was approved by our Institutional Review Board (No. 3516). Informed consent was obtained from all individual participants included in this study. The biopsy specimens were obtained using a novel slim biopsy forceps (Radial Jaw 4P, Boston Scientific, Boston, MA, United States). RESULTS The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 69.6%, 100%, 100%, 59.1%, and 78.8%, respectively. The sensitivity was 75.6% in bile duct cancer, 64% in pancreatic cancer, 61.1% in gallbladder cancer, and 57.1% in metastasis. In bile duct cancer, a lower sensitivity was observed for perihilar bile duct stricture (68.7%) than for distal bile duct stricture (83.1%). In terms of the stricture lengths of pancreatic cancer, gallbladder cancer, and metastasis, a longer stenosis resulted in a better sensitivity. In particular, there was a significant difference between pancreatic cancer and gallbladder cancer (P < 0.05). One major complication was perforation of the extrahepatic bile duct with bile leakage. CONCLUSION Endoscopic transpapillary biopsy alone using novel slim biopsy forceps is feasible and reliable, but restrictive. Biopsy should be performed in consideration of the stricture level, stricture length, and cancer type.

Hemosuccus pancreaticus diagnosed by contrast-enhanced endoscopic ultrasonography (with video)

Hemosuccus pancreaticus, a condition in which blood is expelled into the duodenum via the main pancreatic duct, is a rare cause of acute gastrointestinal bleeding. The common causes of hemosuccus pancreaticus are a pancreatic pseudoaneurysm and pseudocyst due to chronic pancreatitis. We describe a case of hemosuccus pancreaticus caused by a pancreatic pseudoaneurysm due to chronic pancreatitis, which was diagnosed by contrast-enhanced endoscopic ultrasonography (CE-EUS). A 71-year-old man with a long history of alcohol abuse was referred to our hospital with severe anemia and tarry stools. Laboratory data showed a very low hemoglobin level of 4.8 mg/dL. The patient thus received a blood transfusion. Upper GI endoscopy demonstrated no obvious lesion. Computed tomography (CT) revealed a 4.2-cm cystic mass in the pancreatic head with slight contrast-enhancement in the early phase and strong contrast-enhancement in the late phase (Fig. 1). CT also revealed dilatation of the main pancreatic duct and atrophy in the pancreatic body-tail with some small calcifications. Transabdominal ultrasonography showed a 20-mm anechoic area in the pancreatic head and a color Doppler signal was identified in the area. Since a pseudoaneurysm was suspected, angiography was performed. Angiography of the superior mesenteric artery revealed a slight pooling of a contrast medium corresponding to the anechoic area (Fig. 2). However, this was not a typical finding of a pseudoaneurysm. Two days later, since the patient had obstructive jaundice caused by the compression of the enlarged cyst, endoscopic retrograde cholangiopancreatography was performed for biliary decompression. Notably, a duodenoscope showed hemorrhage from the papilla of Vater (Fig. 2). Thus, after biliary stenting, we performed CE-EUS using Sonazoid to identify the origin of the hemorrhage. A fundamental EUS image showed an anechoic lesion similar to that seen on transabdominal ultrasonography (Video S1). Interestingly, 22 seconds after the contrast injection, microbubbles were clearly shown to go into the small feeding artery flowing into the pancreatic head cavity (Fig. 3, Video S1). As previous angiography failed to detect the small feeding artery flowing into the cavity, we speculated that it might be difficult to perform coil embolization on angiography. In addition, the patient had obstructive jaundice due to cyst compression and already received a 16-unit blood cell transfusion. Thus, the patient underwent emergent pylorus-preserving pancreatoduodenectomy as essential therapy. The patient showed good recovery without any adverse events postoperatively. Macroscopic findings showed excessive blood clot in the pancreatic head cavity (Fig. 4). Microscopic specimens showed hemorrhage originating from the ruptured small artery, which flowed into the pancreatic head cavity of which a small portion was covered with an epithelium (Fig. 4). The final diagnosis was hemosuccus pancreaticus derived from a pseudoaneurysm. To the best of our knowledge, this is first report of hemosuccus pancreaticus due to a ruptured artery diagnosed by CE-EUS. CE-EUS may also have other potential applications such as for the close examination of vascular K. Yamamoto · T. Itoi (*) · T. Horibe Department of Gastroenterology and Hepatology, Tokyo Medical University Hospital, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan e-mail: itoi@tokyo-med.ac.jp

Novel ex-vivo training model for free-hand insertion using a double-bending peroral direct cholangioscope

Several experts of direct peroral videocholangioscopy (D‐PVCS) using a conventional ultraslim endoscope have reported its usefulness for the diagnosis and therapy of biliary tract diseases. We have additionally developed a dedicated double‐bending D‐PVCS technique for freehand scope insertion. In this study, we developed an ex vivo training model for the freehand double‐bending D‐PVCS technique and compared it with the technique using a conventional ultraslim endoscope.

Ex vivo assessment of anchoring force of covered biflanged metal stent and covered self-expandable metal stent for interventional endoscopic ultrasound: Anchoring force of covered metal stents

Endoscopic ultrasound (EUS)‐guided transmural drainage using a covered biflanged metal stent (CBFMS) and a conventional tubular biliary covered self‐expandable metal stent (CSEMS) has recently been performed by EUS experts. However, appropriate traction force of the sheath to prevent the migration during stent deployment is well unknown. Herein, we assessed the anchoring force (AF) of the distal flange in CBFMSs and CSEMSs.

The Role of Endoscopic Ultrasound-guided Drainage for Autoimmune Pancreatitis-associated Pancreatic Cysts: A Report of Five Cases and a Literature Review

Objective Autoimmune pancreatitis (AIP) has been recognized as a benign disease, which that shows a prompt response to corticosteroid treatment (CST). It was previously believed to not be associated with cyst formation; however, a few cases of AIP-associated pancreatic cyst (PC) have been reported. Some cases were reported to have been effectively treated by CST, while others were refractory to CST. Many of the patients received interventional treatment. Until now, there has been no consensus on the therapeutic strategies for AIP-associated PC. The aim of the present study is to describe a therapeutic strategy for this condition. Methods We conducted a retrospective study of 5 cases of AIP-associated PC that were treated by endoscopic ultrasonography-guided pancreatic fluid collection drainage (ESPD) or CST at Tokyo Medical University Hospital between March 2012 and October 2016, analyzed the therapeutic outcomes, and performed a literature review. Results The initial treatments included CST (n=2) and ESPD (n=3). All of the PCs disappeared after treatment In 1 of the patients who received CST case and 3 of the patients who received ESPD; however, the PC did not disappear in one of the patients who received CST (corticosteroid maintenance therapy), even after the dose of corticosteroids was increased; ESPD was eventually performed and the PC disappeared. There were no procedure-related complaints. Conclusion We propose that CST be administered as the first-line treatment for AIP-associated PC, particularly in cases of PC without a history of CST. However, ESPD can be applied to treat cases of corticosteroid refractory PC.

Evaluation of a new stent for EUS-guided pancreatic duct drainage: long-term follow-up outcome

Background and study aims  Endoscopic ultrasonography-guided pancreatic duct drainage (EUS-PD) has been reported as an alternative for failed conventional endoscopic retrograde cholangiopancreatography (ERCP). However, there are few dedicated devices for EUS-PD. Recently, we have developed a new plastic stent dedicated to EUS-PD and have conducted a feasibility study to evaluate its efficacy. In the current study, we evaluated the long-term efficacy of this new plastic stent. Patients and methods  Thirty patients (61 ± 14.3 years old, 14 men) with acute recurrent pancreatitis caused by a stricture in the main pancreatic duct (MPD) or stenotic pancreatoenterostomy were treated at our institution using our recently developed 7Fr plastic stent between August 2013 and April 2017. Results  The stent was placed successfully in all patients (30/30) and early clinical success was achieved in all of them. Early adverse events (AEs) occurred in seven patients (23.3 %), namely, self-limited abdominal pain (n = 5), mild pancreatitis (n = 1), and bleeding which required transcatheter arterial embolization (n = 1). Two patients died of primary disease and three were lost to follow-up. The remaining 25 patients were followed up after initial EUS-PD for a median of 23 months (range, 6 – 44 months). Twenty patients required regular stent exchange (3 times; range, 1 – 12 times). Spontaneous stent dislodgement was observed in six patients. Four patients wanted their stents removed 1 year after the initial intervention. Twelve patients (48 %) had regular stent exchange 1 year after the initial intervention. Three patients converted to standard transpapillary pancreatic duct stenting by conventional ERCP. Finally, nine patients (36 %) had complete stent removal either intentionally or by spontaneous dislodgement without any symptoms. Conclusion  The new plastic stent for EUS-PD was associated with not only short-term technical success but also long-term clinical success in the majority of patients evaluated in this study.