Long-term outcomes after EUS-guided antegrade intervention for benign bilioenteric anastomotic stricture.

BACKGROUND AND AIMS: Bilioenteric anastomotic stricture (BES) is a well-known adverse event after bilioenterostomy. Recently, EUS-guided antegrade intervention (EUS-AI) has been developed for cases that are difficult to treat by balloon enteroscopy-assisted ERCP. However, no data are available on the long-term outcomes after EUS-AI. The main goal of the present study was to clarify the long-term outcomes of EUS-AI in such patients. METHODS: Between November 2013 and November 2021, 34 patients who were followed for more than 1 year after EUS-AI for BES were identified. The primary endpoint was the rate of stricture resolution. Secondary endpoints were factors associated with stricture resolution, rate of BES recurrence, rate of conversion to surgery, and rate of hepatic fibrosis progression during follow-up. RESULTS: The median follow-up period was 56.7 months. Stricture resolution was achieved in 17 of 34 patients (50%). A multivariate analysis confirmed that the presence of bile duct stones (odds ratio, 9.473; 95% confidence interval, 1.66-53.98; P = .01) was significantly associated with stricture resolution. The stricture recurrence rate was 33%, and the median time from stent removal to recurrence was 31.2 months. Four patients underwent surgery because of recurrent cholangitis. During the median follow-up period of 56.7 months, 25% progressed to hepatic fibrosis based on the Fibrosis-4 index grade. Interestingly, patients without cholangitis during follow-up did not show progression of hepatic fibrosis. CONCLUSIONS: EUS-AI has achieved acceptable long-term clinical outcomes. EUS-AI can be a viable alternative treatment of choice before surgical treatment in patients who are difficult to treat by conventional approaches.

Long-term outcomes of EUS-guided balloon-occluded gastrojejunostomy bypass for malignant gastric outlet obstruction (with video).

BACKGROUND AND AIMS: EUS-guided gastroenterostomy (EUS-GE) is a minimally invasive technique for gastric outlet obstruction (GOO). EUS-guided balloon-occluded gastrojejunostomy bypass (EPASS) aims to improve stent deployment and minimize migration in EUS-GE. In this study, we evaluated the long-term outcomes of EPASS. METHODS: We retrospectively analyzed 37 patients (mean age, 71 years; 21 men) with symptomatic, nonrefractory GOO who had undergone EPASS. RESULTS: EPASS achieved a 94.6% technical success rate (35/37), including 2 cases of stent misdeployment. The mean procedure time was 27.3 minutes, with a double-balloon tube insertion time of 10.4 minutes. Initial GOO scores improved from .43 to 2.14 and 2.60 at 7 and 28 days after EPASS, respectively. The clinical success rate was 89.2%. The rate of adverse events, including fever and abdominal pain, was 16.2%. The mean overall survival after EPASS was 193.5 days, with no stent occlusion or migration (100% patency). CONCLUSIONS: EPASS demonstrated safety and reliability in EUS-GE, offering a viable option for symptomatic malignant GOO treatment. (Clinical trial registration number: UMIN000011608.).

A single-institution retrospective study of comprehensive genomic profiling tests based on C-CAT findings for advanced solid cancers.

BACKGROUND: In recent years, as the availability of precision therapies expands, there is increasing reliance on genomic profiling assays to help identify the most appropriate treatment options for patients with advanced cancers. We retrospectively investigated the results of comprehensive genomic profiling tests from the time insurance coverage began until recently and examined the status of genetic analysis. METHODS: We retrospectively reviewed the analysis results of 300 patients with advanced solid tumors who consented to comprehensive genomic profiling tests from October 2019 to December 2022. RESULTS: Of the 300 patients who underwent comprehensive genomic profiling tests, analysis results for 274 patients were obtained, and were reviewed by the Clinical Genome Expert Panel. Six specimens (2%) were discontinued due to patient deaths and deteriorations in general condition. The three most frequently occurring actionable genomic alterations observed were TP53 (47.4%), KRAS (28.1%) and CDKN2A (20.4%). The most common druggable variant was CDKN2A, which was noted in 52 (19%) of 274 patients. The next most common were PIK3CA, BRAF, KRAS and PTEN. The cancer types that showed a greater median number of actionable alterations comprised thyroid cancer, pancreatic cancer and colorectal cancer. CONCLUSIONS: In conclusion, comprehensive genomic profiling tests have the potential to be valuable in identifying genomic abnormalities. Even if there is no effective treatment at present, it may lead to a treatment in the future. Comprehensive genomic profiling tests should be considered for any cancer.

Urgent and emergency endoscopic retrograde cholangiopancreatography for gallstone-induced acute cholangitis and pancreatitis.

Urgent or emergency endoscopic retrograde cholangiopancreatography (ERCP) is indicated for gallstone-induced acute cholangitis and pancreatitis. The technique and optimal timing of ERCP depend on the disease state, its severity, anatomy, patient background, and the institutional situation. Endoscopic transpapillary biliary drainage within 24 h is recommended for moderate to severe acute cholangitis. The clinical outcomes of biliary drainage with nasobiliary drainage tube placement and plastic stent placement are comparable, and the choice is made on a case-by-case basis considering the advantages and disadvantages of each. The addition of endoscopic sphincterotomy (EST) is basically not necessary when performing drainage alone, but single-session stone removal following EST is acceptable in mild to moderate cholangitis cases without antithrombotic therapy or coagulopathy. For gallstone pancreatitis, early ERCP/EST are recommended in cases with impacted gallstones in the papilla. In some cases of gallstone pancreatitis, a gallstone impacted in the papilla has already spontaneously passed into the duodenum, and early ERCP/EST lacks efficacy in such cases, with unfavorable findings of cholangitis or cholestasis. If it is difficult to diagnose the presence of gallstones impacted in the papilla on imaging, endoscopic ultrasonography can be useful in determining the indication for ERCP.

Optimal mode and power output of electrosurgical units for endoscopic papillectomy based on animal experiments and a preliminary clinical study (with videos).

BACKGROUND AND AIMS: The optimal electrosurgical unit (ESU) settings for endoscopic papillectomy (EP) have not been investigated. We conducted animal experiments to determine the optimal endoCUT settings with VIO (Erbe, Tübingen, Germany) ESUs and then conducted a small clinical study. METHODS: Dedicated animal experimental models were created. To investigate the incision force, chicken meat was resected with a snare whose handle was a hung weight. To investigate the coagulation effect, a surgical needle electrode was inserted into a pig liver and energized, and to determine changes over time in the coagulation status, simulated EP was performed using a living pig. These experiments were performed using the knife-setting or snare-setting endoCUT modes and various effect, duration, and interval settings and compared with results for ICC (Erbe) ESUs. Based on the results, we performed EP in a small number of patients. RESULTS: The main factor affecting the incision force was duration. The coagulation effect was related to not only effect but also duration. In the endoCUT mode, knife-setting produced a higher incision force and lower coagulation effect. The nondischarge coagulation effect may cause deep ulceration. Based on the animal experiments, we concluded the ideal ESU setting for EP, "VIO EP mode," is knife-setting with high duration, lowest effect, and low interval settings. In the clinical study, there were no significant adverse events such as bleeding, pancreatitis, or perforation. CONCLUSIONS: "VIO EP mode" seems to afford optimal papillectomy. Larger scale clinical studies are needed to accumulate further data and make clinical comparisons with the ICC ESU.

New deployment techniques of the lumen-apposing metal stent in walled-off necrosis filled with necrotic tissue: Chick opening its mouth (with video).

The lumen-apposing metal stent (LAMS) on an electrocautery-enhanced delivery system for endoscopic ultrasound-guided transluminal drainage has been widely used for the treatment of walled-off necrosis (WON). However, deployment of the LAMS can be technically difficult in WON, which contains a large amount of necrotic tissue and a low liquid component, owing to insufficient space for expansion of the distal stent flange. It has been recommended that the LAMS is placed in WON containing necrotic tissue, because additional endoscopic necrosectomy can be readily performed via the lumen of the LAMS. Here we introduce two new deployment techniques of the LAMS for WON filled with necrotic tissue, namely, the two-step puncture technique and the back-and-forth technique, which enable the distal stent flange to be expanded like a chick opening its mouth. These techniques are expected to further improve the clinical outcomes of refractory WON.

[A case of mucinous cystadenoma of the pancreas changed from multilocular to unilocular with cyst in cyst structure with an 8-year follow-up].

A 57-year-old woman presented with multilocular cysts like a bunch of grapes, 30mm in diameter, in the tail of the pancreas. The number of cysts has increased, and each one had grown. Eventually, they turned into a unilocular cyst with a cyst in the cyst structure of about 50mm in diameter. Laparoscopic distal pancreatectomy was performed, and the resected specimen was diagnosed with mucinous cystadenoma. We report the rare morphological change in this case and consider the mechanism of its occurrence based on pathological considerations.

[A case of distal bile duct carcinoma converted to neuroendocrine cancer and proliferated into the pancreas].

A woman in her 50s was referred due to a solid mass in the head of the pancreas. It was diagnosed as a neuroendocrine carcinoma (NEC) by endoscopic ultrasound-guided fine-needle aspiration. Consequently, pancreatoduodenectomy was performed. A well-differentiated adenocarcinoma component was revealed in the resected bile duct, suggesting a relationship with the NEC component in the pancreas. Genetic examination suggested that cholangiocarcinoma, but not coexisting carcinoma, was converted to NEC after the interstitial invasion. Finally, it was diagnosed as the NEC derived from the extrahepatic bile duct, which is rare at about 0.2-2% in gastrointestinal neuroendocrine neoplasms.

Impact of electrical pulse cut mode during endoscopic papillectomy: Pilot randomized clinical trial.

OBJECTIVE: Endoscopic papillectomy is increasingly being used for ampullary adenoma treatment. However, it remains challenging despite increased safety with treatment advances. The ideal power output and electrosurgical current mode for mucosal resection are not established. We aimed to identify the ideal electrical pulse for use during resection. METHODS: This pilot randomized, single-blind, prospective, multicenter trial, recruited patients with ampullary adenomas and conventional anatomy who were scheduled to undergo endoscopic papillectomy. Endoscopic treatment was performed using a standardized algorithm and patients were randomized for endoscopic papillectomy with Endocut or Autocut. The primary outcome was the incidence of delayed bleeding. Incidence of procedure-related pancreatitis, successful complete resection, pathological findings, and other adverse events were secondary endpoints. RESULTS: Sixty patients were enrolled over a 2-year period. The incidences of delayed bleeding (13.3% vs. 16.7%, P = 1.00) and pancreatitis (27% vs. 30%, P = 0.77) were similar between both groups. The rate of crush artifacts was higher in the Endocut than in the Autocut group (27% vs. 3.3%, P = 0.03). Immediate bleeding when resecting tumors greater than 14 mm in diameter was more common in the Autocut than in the Endocut group (88% vs. 46%, P = 0.04). CONCLUSIONS: The Autocut and Endocut modes have similar efficacy and safety for endoscopic papillectomy. The Endocut mode may prevent immediate bleeding in cases with large tumor sizes, although it causes more frequent crush artifacts. REGISTRY AND THE REGISTRATION NUMBER: The Japanese UMIN Clinical Trials Registry (UMIN-CTR: 000021382).

EUS-guided antegrade intervention for benign biliary diseases in patients with surgically altered anatomy (with videos).

BACKGROUND AND AIMS: Although balloon enteroscopy-assisted ERCP (BE-ERCP) is effective and safe for benign biliary diseases in patients with surgically altered anatomy (SAA), BE-ERCP is not always successful. Recently, EUS-guided antegrade intervention (EUS-AI) by using a 1-stage or 2-stage procedure has been developed for BE-ERCP failure cases. The aim of the present study was to evaluate the outcome of EUS-AI for benign biliary diseases in patients with SAA. METHODS: Of 48 patients in whom BE-ERCP failed, percutaneous transhepatic intervention was performed in 11. From November 2013 until November 2017, we retrospectively reviewed cases of an additional 37 patients with SAA who failed BE-ERCP and underwent EUS-AI for benign biliary diseases (common bile duct stones [n = 11], intrahepatic bile duct stones [n = 5], anastomotic strictures [n = 21]). RESULTS: The overall technical success of the creation of the hepatoenteric tract by EUS was 91.9% (34/37). Moderate adverse events were observed in 8.1% (biliary peritonitis [n = 3]). One-stage EUS-AI by EUS succeeded in 8 cases (100%) without any adverse events. In another 26 cases, 2-stage EUS-AI by ERCP was performed about 1 or 2 months later. Endoscopic antegrade therapy under fluoroscopy was successful in 6 cases. Per-oral cholangioscopy-assisted antegrade intervention was required in 19 cases (guidewire manipulation across the anastomotic stricture [n = 6], cholangioscopy-guided lithotripsy by using electrohydraulic lithotripsy [n = 13]). In 1 case, magnetic compression anastomosis was performed. The final clinical success rate of all EUS-AIs was 91.9%. CONCLUSIONS: EUS-AI for benign biliary diseases in patients with SAA appears to be a feasible and safe alternative procedure after BE-ERCP failure.

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

BACKGROUND AND AIMS: 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. METHODS: The AFs of four CBFMSs (Stents AX, NG, PL, and SX) and six CSEMSs (Stents BF, BP, EG, HN, SP, and WF) were compared in an ex vivo setting. We assessed the AF produced by each stent using an EUS-guided transmural drainage model and an EUS-guided hepaticogastrostomy model consisting of sheet-shaped specimens of the stomach, gelatin gel, and gelatin tubes. RESULTS: For CBFMSs, the maximum AF of Stent AX was significantly higher than those of Stents PL and SX (P < 0.05) in the porcine model. In the gelatin series, all stents except Stent NG showed a nearly similar AF. For CSEMSs, Stents HN, EG, BF, and WF showed gradual AF elevation in the porcine stomach. Stents SP and BP showed a lower AF than the other four stents. For the gelatin setting, the maximum AF of Stents HN, EG, and WF was higher than those of the other stents regardless of the type of specimens. CONCLUSIONS: The significance of the AF and traction distance according to the property of various CBFMSs and CSEMSs could be elucidated using ex vivo models.

Expanding the indication of endoscopic papillectomy for T1a ampullary carcinoma.

BACKGROUND AND AIM: Endoscopic papillectomy (EP) has been attempted not only for benign lesions but also for early ampullary carcinoma (AC). However, there is still no sufficient evidence or consensus regarding the effectiveness of EP for early AC. Herein, we evaluated the expanding indication of EP for early AC. METHODS: Between May 1999 and December 2016, 177 patients were diagnosed with ampullary tumor before undergoing EP, and their clinical and histopathological data were analyzed retrospectively. RESULTS: There were 27 Tis-T1a AC patients and four T1b AC patients who underwent EP. Mean tumor size was 14.1 mm for Tis-T1a AC and 17.0 mm for T1b AC. For the histological grade, 50% (2/4) of T1b AC were moderately differentiated, whereas 96.3% (26/27) of Tis-T1a AC were well differentiated and papillary. For lymphovascular invasion, one (25%) occurred in T1b AC but none occurred in Tis-T1a AC. There was no AC recurrence from the date of EP until a maximum of 5 years (Tis-T1a: mean period 48.5 months [5-60]; T1b: mean period 26.5 months [3-60]). CONCLUSIONS: Endoscopic papillectomy is useful and reliable for the curative treatment of T1a AC. Large-scale prospective studies with long-term follow up are needed.

Novel peroral direct digital cholangioscopy-assisted lithotripsy using a monorail technique through the overtube in patients with surgically altered anatomy (with video).

Efficacy of cholangioscopy-assisted lithotripsy for difficult stones such as huge stones, multiple large stones and an impacted stone in patients with non-altered anatomy has been reported. Herein, we describe peroral direct digital cholangioscopy (PDCS)-assisted electrohydraulic lithotripsy (EHL) with a new technique in patients with surgically altered anatomy. Five patients received PDCS-assisted EHL with the monorail technique due to failed conventional stone extraction. Balloon enteroscope was removed, leaving the stiff guidewire in the bile duct and an overtube with inflated balloons. The cholangioscope was then inserted into the bile duct over the wire through the overtube. After direct visualization of the stone, PDCS-assisted EHL was carried out. This technique was named the 'monorail technique'. Complete removal of biliary stones in one session was accomplished in four patients and only one case required two sessions. There was no adverse event in any of the cases. PDCS-assisted EHL using the monorail technique was effective and safe for difficult biliary stones in patients with surgically altered anatomy.

Novel ex vivo training model for freehand insertion using a double-bending peroral direct cholangioscope.

BACKGROUND AND AIM: 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. METHODS: The ex vivo model was made for training using a U-shape insertion pattern. A third prototype endoscope and an ultraslim upper gastrointestinal endoscope were used. Two experts and nine non-experts performed D-PVCS using the freehand technique. RESULTS: The two experts could not advance the tip of the endoscope to the hilar portion using the freehand technique, but they could achieve technical successful insertion to the hilar portion with the third prototype cholangioscope using the freehand technique alone. The non-experts could not advance the tip of the endoscope to the bile duct using the freehand technique. On the other hand, two (22.2%) non-experts could advance the tip of the third prototype cholangioscope using the freehand technique before the training conducted by the experts. After the training, all the non-experts could advance the tip of the third prototype cholangioscope to the hilar portion. CONCLUSIONS: The novel ex vivo model using a third prototype cholangioscope was useful for training in the use of the freehand D-PVCS technique.

Prospective evaluation of a new biflanged metal stent for the treatment of pancreatic fluid collections (with videos).

BACKGROUND AND AIMS: EUS-guided transluminal drainage (EUS-TD) and sequential direct endoscopic necrosectomy (DEN) for pancreatic fluid collections (PFCs) by using a dedicated biflanged metal stent (BFMS) has been reported as a useful alternative to using plastic stents or a conventional metal stent. However, current dedicated BFMSs have limitations. Recently, a new BFMS with solidly constructed biflanges and various stent lengths matched to the PFC condition has been developed. Herein, we prospectively evaluated this new BFMS for the treatment of PFCs. METHODS: From July 2015 to July 2016, EUS-TD by using the new BFMS was performed in 12 patients for PFCs (4 patients with pancreatic pseudocysts, 8 patients with walled-off necrosis). When clinical resolution could not be achieved, DEN was performed the following day. RESULTS: The stent was deployed successfully with a median procedure time of 16 minutes (range 11-24 minutes) and with no procedure-related adverse events in any patients (12/12, 100%). DEN via the stent was achieved in all patients in whom they were attempted (4/4,100%). Spontaneous stent migration or stent dislocation during DEN was not observed in any patients. Two WON patients died from spontaneous pseudoaneurysm rupture and multiple organ failure. The PFCs in the other 10 patients completely resolved, and later the stent was removed with no difficulty in 9 patients after a median time of 48 days (range 30-180 days). CONCLUSIONS: The new BFMS is technically feasible and safe for the treatment of PFCs. (Clinical trial registration number: UMIN000021347.).

Endoscopic management of acute cholangitis according to the TG13.

The Tokyo Guidelines 2013 (TG13) recommend that endoscopic drainage should be the first-choice treatment for biliary decompression in patients with acute cholangitis. Timing of biliary drainage for acute cholangitis should be based on the severity of the disease. For patients with severe acute cholangitis, appropriate organ support and urgent biliary drainage are needed. For patients with moderate acute cholangitis, early biliary drainage is needed. For patients with mild acute cholangitis, biliary drainage is needed when initial treatment such as antimicrobial therapy is ineffective. There are three methods of biliary drainage: endoscopic drainage, percutaneous transhepatic drainage, and surgical drainage. Endoscopic drainage is less invasive than the other two drainage methods. The drainage method (endoscopic nasobiliary drainage and stenting) depends on the endoscopist's preference but endoscopic sphincterotomy should be selected rather than endoscopic papillary balloon dilation from the aspect of procedure-related complications. In the TG13, balloon enteroscopy-assisted and endoscopic ultrasound-guided biliary drainages have been newly added as specific drainage methods. Recent studies have demonstrated their usefulness and safety. These drainage methods will become more widespread in the future.

Serum Metabolomic Profiles for Human Pancreatic Cancer Discrimination.

This study evaluated the clinical use of serum metabolomics to discriminate malignant cancers including pancreatic cancer (PC) from malignant diseases, such as biliary tract cancer (BTC), intraductal papillary mucinous carcinoma (IPMC), and various benign pancreaticobiliary diseases. Capillary electrophoresismass spectrometry was used to analyze charged metabolites. We repeatedly analyzed serum samples (n = 41) of different storage durations to identify metabolites showing high quantitative reproducibility, and subsequently analyzed all samples (n = 140). Overall, 189 metabolites were quantified and 66 metabolites had a 20% coefficient of variation and, of these, 24 metabolites showed significant differences among control, benign, and malignant groups (p < 0.05; Steel-Dwass test). Four multiple logistic regression models (MLR) were developed and one MLR model clearly discriminated all disease patients from healthy controls with an area under receiver operating characteristic curve (AUC) of 0.970 (95% confidential interval (CI), 0.946-0.994, p < 0.0001). Another model to discriminate PC from BTC and IPMC yielded AUC = 0.831 (95% CI, 0.650-1.01, p = 0.0020) with higher accuracy compared with tumor markers including carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), pancreatic cancer-associated antigen (DUPAN2) and s-pancreas-1 antigen (SPAN1). Changes in metabolomic profiles might be used to screen for malignant cancers as well as to differentiate between PC and other malignant diseases.

Balloon enteroscopy-assisted ERCP in patients with Roux-en-Y gastrectomy and intact papillae (with videos).

BACKGROUND AND AIMS: Balloon enteroscopy-assisted ERCP has provided a marked improvement in the success rate of reaching the papilla and consecutive ERCP procedures in patients with surgically altered anatomy in the Roux-en-Y reconstruction setting. However, limited data are available on the outcome of balloon enteroscopy-assisted ERCP in patients with Roux-en-Y anatomy who have naïve papillae. We retrospectively evaluated the feasibility of balloon enteroscopy-assisted ERCP in Roux-en-Y reconstruction after total or subtotal gastrectomy (RYG) with native papillae. METHODS: We performed 123 ERCP procedures in 109 patients with RYG. Among these patients, 90 consecutive ERCPs in 90 patients with native papillae were included. When selective biliary cannulation failed, the double-guidewire technique, the precut technique, or the rendezvous technique were performed as advanced cannulation methods. RESULTS: The overall success rate of reaching the papilla was 93.5% (115/123). The total procedure success rate was 88.1% (96/109). The adverse event rate was 7.3% (8/109). The success rate of the standard cannulation of the intact papilla was 67.8% (61/90). The final cannulation success rate was 95.6% (86/90) by using advanced cannulation methods. CONCLUSIONS: Standard cannulation of the intact papilla in RYG cases remains challenging and uncertain. The use of various advanced cannulation methods improves the deep cannulation rate. Once selective cannulation succeeds, the treatment success rate is very high.