A Prospective Multicenter Study of a Fully Covered Metal Stent in Patients with Distal Malignant Biliary Obstruction: WATCH-2 Study.

BACKGROUND: Both fully covered (FC) and partially covered (PC) self-expandable metal stents (SEMSs) are now commercially available for distal malignant biliary obstruction (MBO). While FCSEMS can be easily removed at the time of re-interventions, it is theoretically prone to migration. However, few comparative data between FC and PC SEMSs have been reported. AIMS: The aim of this study was to compare clinical outcomes of FCSEMS with those of PCSEMS. METHODS: This was a multicenter, prospective study of FCSEMS for unresectable distal MBO with a historical control of PCSEMS, which was previously reported as the WATCH study. The primary outcome was recurrent biliary obstruction (RBO), and secondary outcomes were stent migration, stent removal, stent-related adverse events, and survival. RESULTS: A total of 151 cases with unresectable distal MBO undergoing FCSEMS placement were enrolled and compared with a historical cohort of 141 cases undergoing PCSEMS placement. No significant differences were found in the rate of RBO (29 vs. 33%; P = 0.451), time to RBO (318 vs. 373 days; P = 0.382), and survival (229 vs. 196 days; P = 0.177) between FCSEMS and PCSEMS. The rate of stent migration also did not differ significantly between the two groups (14 vs. 8%; P = 0.113). The removal of FCSEMSs was successful in all 24 attempted cases (100%). CONCLUSIONS: FCSEMSs appeared comparable to PCSEMSs in terms of RBO without a significant increase in stent migration rate in patients with unresectable distal MBO. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000007131.

A case of intraductal papillary neoplasm of the bile duct preoperatively diagnosed using contrast-enhanced endoscopic ultrasonography.

A 71-year-old man was referred to our hospital and was diagnosed with jaundice and a liver function disorder. Although we suspected an intraductal papillary neoplasm of the bile duct (IPNB)-derived caudate branches on the basis of contrast-enhanced CT, MRI, and endoscopic retrograde cholangiopancreatography, we could not clearly identify the tumor. Therefore, we examined the lesion using endoscopic ultrasonography (EUS). We could visualize an iso-hyperechoic elevated tumor in the caudate branches. The tumor was observed as a hypervascular lesion using contrast-enhanced EUS, which is useful in preoperatively diagnosing IPNB and detecting the presence of lesions.

Delayed perforation after cold snare polypectomy for small colonic polyps in a patient receiving oral corticosteroids.

This case report describes a fatal outcome due to delayed perforation after cold snare polypectomy in a patient with bullous pemphigoid receiving oral corticosteroids. Cold snare polypectomy has become the standard treatment for small colorectal polyps because of the procedure's safety and simplicity. In this case, however, corticosteroid therapy and vasculitis may have caused local necrosis and tearing of the intestinal wall. Corticosteroids are widely used, and perforation after cold snare polypectomy is extremely rare. However, some patients on corticosteroid therapy may have special pathologies, such as in this case, and we advise physicians to use appropriate judgment and extreme caution in determining the indication for endoscopic therapy.

Genetic diagnosis of pancreatic cancer using specimens obtained by EUS-FNA.

We review the current situation concerning molecular biological analysis in respect of pancreatic cancer, using specimens obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). K-ras, p53, p16, DPC4/SMAD4, telomerase activity are used for discrimination between tumor-forming pancreatitis and pancreatic cancer. Examination of heat shock protein (HSP) 27, ribonucleotide reductase, and other factors are examined in order to test the sensitivity to Gemcitabin. Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by EUS-FNA was reported to be useful for evaluate the biological characteristics of pancreatic cancer before treatment. It is expected that the genetic diagnosis using EUS-FNA specimens will not only positively contribute to improving the diagnostic performance, but it will also provide valuable information for carrying out tailor-made treatment.

Unilateral versus bilateral drainage using self-expandable metallic stent for unresectable hilar biliary obstruction.

BACKGROUND: There is no consensus on the choice of either unilateral or bilateral drainage in stent placement for patients with unresectable hilar biliary obstruction. The aim of the present study was to clarify which drainage method is superior. METHODS: We retrospectively reviewed 82 patients with hilar biliary obstruction who underwent metallic stenting. These patients were divided into a unilateral drainage group (Uni group) and a bilateral drainage group (Bi group). RESULTS: There was no significant difference between the groups in median survival time, median stent patency period, and median complication-free survival time. The most frequent complication was stent obstruction, followed by cholangitis. Liver abscess was found at a higher frequency in the Bi group (17.6%) than in the Uni group (1.5%) (P=0.0266). There was no significant difference between the groups in the occurrence of two or more complications (P=0.247), life-threatening severe complications (P=0.0577), and stent obstruction by sludge (P=0.0912). CONCLUSION: When compared with bilateral biliary drainage, unilateral biliary drainage is associated with a lower incidence of liver abscess as well as a comparable outcome of stent patency time and complication-free survival. We therefore propose that hilar biliary obstruction can be treated first by unilateral drainage with a metallic stent and by bilateral drainage only in patients who develop cholangitis in the contralateral biliary tree.

Successful retrieval of an impacted mechanical lithotripsy basket: a case report.

We report the successful retrieval of an impacted mechanical lithotripsy basket. In a patient with two large common bile duct stones, the basket with the entrapped stone was impacted within the mid-common bile duct. We then attempted to use another mechanical lithotripter; however the central wire of the basket fractured at the handle portion. Grasping a few wires of the impacted basket with rat-tooth forceps allowed the wires of the basket to slip away from the stone. The present report describes the safe and effective use of rat-tooth forceps in the management of an impacted lithotripter basket.

Double balloon endoscope facilitates endoscopic retrograde cholangiopancreatography in roux-en-y anastomosis patients.

Endoscopic retrograde cholangiopancreatography (ERCP) is the gold standard for the treatment of patients with pancreaticobiliary disorders, but endoscopic therapy is very difficult to carry out in patients with a Roux-en-Y anastomosis. We herein present the results of ERCP for patients with a Roux-en-Y anastomosis using a double-balloon endoscope. Six patients (six men with a mean age of 69 years) who had undergone prior gastric resection with Roux-en-Y reconstruction were enrolled in the present study and underwent ERCP and associated procedures. ERCP was carried out with a double balloon endoscope, which has one balloon attached to the tip of the endoscope and another attached to the distal end of the soft overtube. In all patients, entering the Y loop was successfully accomplished, and the papilla of Vater was also reached in all cases (100%). Cannulation was successful in four patients (66.7%). The final diagnosis was choledocholithiasis in two patients, biliary fistula in one patient and pancreatic cancer in one patient. A needle-knife precut papillotomy was carried out after placement of a bile duct stent in two patients, and injection of N-butyl-2-cyanoacrylate into a biliary fistula was carried out in one patient. None of the patients suffered from any complications. A double balloon endoscope is therefore considered to be useful for carrying out ERCP and associated procedures in patients with a Roux-en-Y anastomosis.

Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance.

BACKGROUND: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). METHODS: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. RESULTS: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. CONCLUSIONS: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.

ERCP using double-balloon endoscopes in patients with Roux-en-Y anastomosis.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) and associated procedures are difficult to perform in patients with a Roux-en-Y reconstruction. Therefore, at present, at many institutions, ERCP is not generally performed for those with a Roux-en-Y anastomosis. METHODS: However, double-balloon endoscopes (DBEs) have dramatically changed this situation. RESULTS: The use of a DBE enables an endoscopic approach into the deeply situated small intestine, which has been difficult with a conventional endoscope. Therefore, ERCP for patients with a Roux-en-Y anastomosis has been attempted using a DBE, and good results have been reported. CONCLUSION: The development of DBEs has created the possibility of performing ERCP for patients with Roux-en-Y reconstruction in whom an endoscopic approach has conventionally been believed to be difficult.

The usefulness of wire-guided endoscopic snare papillectomy for tumors of the major duodenal papilla.

OBJECTIVES: Although endoscopic papillectomy is useful for treating papillary tumors, it is associated with a high rate of complications including pancreatitis; therefore, safer treatment options are needed. We examined the utility of wire-guided endoscopic papillectomy by comparing the pancreatic duct stenting and pancreatitis rates before and after wire-guided endoscopic papillectomy was introduced at our institution. METHODS: We retrospectively examined the data from 16 consecutive patients who underwent conventional endoscopic papillectomy between November 1995 and July 2005 and the data from 33 patients in whom wire-guided endoscopic papillectomy was first attempted at our institution between August 2005 and April 2017. We compared the pancreatic duct stenting and pancreatitis rates between the two groups. RESULTS: Of the 33 patients in whom wire-guided endoscopic papillectomy was first attempted, the procedure was completed in 21. Pancreatic duct stenting was possible in 30 of the 33 patients in whom wire-guided endoscopic papillectomy was attempted (91%), and this rate was significantly higher than that before the introduction of wire-guided endoscopic papillectomy (68.8%). The incidence of pancreatitis before the introduction of wire-guided endoscopic papillectomy was 12.5%, but after August 2005, the incidence was reduced by half to 6.1%, which includes those patients in whom wire-guided endoscopic papillectomy could not be completed. CONCLUSIONS: Although wire-guided endoscopic papillectomy cannot be completed in some patients, we believe that this method shows some potential for reducing the total incidence of post-endoscopic papillectomy pancreatitis owing to more successful pancreatic duct stenting.

Usefulness of endoscopic ultrasound-guided fine needle aspiration for lymphadenopathy.

Lymphadenopathy may be difficult to diagnose using imaging results alone. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) may help to diagnose and determine the appropriate management of lymphadenopathy. EUS-FNA has been used as a safe and less invasive method for obtaining pathologic specimens from extraluminal lesions using endoscopic ultrasound. The present study evaluated the usefulness of EUS-FNA for lymphadenopathy. Between July 2013 and December 2016, 72 patients undergoing EUS-FNA for lymphadenopathy that could not be diagnosed solely using imaging were included. The present study evaluated the sensitivity, specificity, positive and negative predictive value, overall accuracy, helpfulness in determining the management of lymphadenopathy and EUS-FNA-associated complications. Of the 72 included patients, 8 were diagnosed with benign (inflammatory or reactive) lymphadenopathy. The diagnostic sensitivity, specificity, positive and negative predictive value, and overall accuracy were 95.3, 100, 100, 72.7 and 95.8%, respectively. While EUS-FNA of metastatic nodes identified the origin in the majority of cases, the procedure resulted in a different histopathological diagnosis from the previous image-based diagnosis in 9 patients. Consequently, 2 patients with testicular cancer were administered bleomycin, etoposide, and cisplatin. An individual with GIST was administered imatinib, and a patient with prostate cancer was administered degarelix (antihormon drug). A total of 5 other patients received palliative medicine due to the change in diagnosis. EUS-FNA also helped determine the appropriate cancer management plan in other patients; specifically, based on the cytology of the metastatic lymph node, EUS-FNA helped determine the cancer stage, and to identify recurrence or the primary cancer from which tissue could not be collected. No EUS-FNA-associated symptoms were reported. To conclude, the present study suggested that EUS-FNA of suspected metastatic lymph nodes appears safe and useful for cancer staging and diagnosing recurrence. It may also useful for diagnosing patients whose collection of samples from the original cancer appeared impractical. EUS-FNA for lymphadenopathy that may not be diagnosed with imaging alone may assist in diagnosis and help to determine the appropriate management strategy.

Usefulness of the "newly designed" short-type single-balloon enteroscope for ERCP in patients with Roux-en-Y gastrectomy: a pilot study.

Background and aims In recent years, the short single-balloon enteroscope (SBE) has been used during endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy and has been reported to be useful. However, difficulties remain, and the procedures and devices need improvements. We assessed the usefulness and superiority of a new short SBE equipped with passive bending and high-force transmission by comparisons with outcomes using the conventional short SBE. Methods This study evaluated short SBE-assisted ERCP-related procedures for Roux-en-Y gastrectomy between September 2011 and October 2017. Outcomes including the procedural success rate, which was the primary outcome, were assessed to compare the conventional short SBE (SIF-Y0004 [prototype]) and the new short SBE (SIF-H290S). Results Of 74 procedures performed in 61 patients, 51 procedures in 39 patients involved the SIF-Y0004, and 23 procedures in 22 patients involved the SIF-H290S. The procedural success rates were 70.6 % for SIF-Y0004, and 95.7 % for SIF-H290S, representing better results for the new short SBE ( P  = 0.02). The new short SBE also had a superior diagnostic success rate ( P  = 0.047) and median time to reach the blind end ( P  < 0.001). Conclusions Roux-en-Y gastrectomy patients treated with the new short SBE had better outcomes than those treated with conventional short SBE. More cases need to be studied; however, the new short SBE has the potential to improve ERCP outcomes in patients with surgically altered anatomy.

Endoscopic removal of laser-cut covered self-expandable metallic biliary stents: A report of six cases.

Covered self-expandable metallic stents (CSEMS) may provide palliative drainage for unresectable distal malignant biliary strictures. Laser-cut CSEMS allows easy positioning due to its characteristic of minimal stent shortening. Endoscopic stent removal is sometimes recommended for recurrent biliary obstruction (RBO). However, there are no previous reports of endoscopic removal of laser-cut CSEMS. The current study presents data from 6 patients who were placed a laser-cut CSEMS for unresectable distal malignant biliary strictures, and later endoscopic stent removal was attempted for RBO at the present institute. The duration of stent placement, the procedural success rate, the procedural duration, and accidental complications were evaluated. The mean duration of stent placement was 156±37.9 days (range, 117-205). The procedural success rate was 100%. The mean procedural duration was 11.8±7.5 min (range, 5-24). No complications were reported. Laser-cut CSEMS were safely removed from all patients. The present case report is the first to demonstrate that Endoscopic stent removal of laser-cut CSEMS was safely performed.

Utility of "liquid biopsy" using pancreatic juice for early detection of pancreatic cancer.

Background Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions Our study indicates the potential of "endoscopic liquid biopsy" to capture the driver gene for PDA diagnosis.

Increased neutrophil-to-lymphocyte ratio is a novel marker for nutrition, inflammation and chemotherapy outcome in patients with locally advanced and metastatic esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer, and its progression is strongly influenced by the presence of inflammation. Recently, there has been growing interest in the host inflammatory response, and increasing evidence has indicated that the neutrophil-to-lymphocyte ratio (NLR), a useful marker of systemic inflammation, may be an effective prognostic indicator in various types of malignant diseases. In the present study, 260 patients with ESCC were enrolled, including 110 who received chemoradiation therapy (CRT) involving irradiation and chemotherapy of 5-fluorouracil and cisplatin, and 150 received chemotherapy using 5-fluorouracil and cisplatin (FP). The patients of each group were both divided into two groups according to their NLR: High NLR (NLR>3.0) and low NLR (NLR≤3.0). Serum levels of prealbumin and retinol binding protein, which are nutritional parameters, were both significantly inversely correlated with NLR in patients treated with CRT, and patients treated with FP. Levels of CRP, a marker of inflammation, were significantly correlated with NLR, and stimulation indices, markers of immune reactions, were inversely correlated with NLR in both of CRT patients and FP patients. In patients treated with CRT, a partial response was significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. In patients treated with FP, a partial response was also significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. The overall survival of patients with CRT and FP were both significantly worse in patients with a high NLR than in those with a low NLR. NLR may serve as a useful marker of the tumor response, immune suppression, malnutrition and prognosis upon CRT or FP in patients with locally advanced or metastatic ESCC.

Clinical impact of endoscopic papillectomy for benign-malignant borderline lesions of the major duodenal papilla.

BACKGROUND AND PURPOSE: The present study retrospectively analyzed the clinical impact of endoscopic papillectomy on the selection of a treatment strategy for patients with benign-malignant borderline lesions of the major duodenal papilla. PATIENTS AND METHODS: Between November 1995 and July 2009, 28 patients were selected for endoscopic papillectomy. The clinical impact of endoscopic papillectomy was assessed. Snare resection was performed in a radical fashion. RESULTS: An endoscopic papillectomy was technically feasible in all patients. En bloc excision was achieved in 22 cases (79%). The final histopathological diagnoses of the endoscopic specimen were 17 adenoma (61%), 7 carcinoma in adenoma (25%), and 4 adenocarcinoma (14%). Two out of the four adenocarcinoma cases were referred for surgery. The other two patients with negative margins have not experienced recurrences during the follow-up period. A residual tumor was detected in 1 out of 17 cases (6%) of adenoma and 2 out of 7 cases (29%) of carcinoma in adenoma. CONCLUSIONS: Endoscopic papillectomy is therefore considered to be an effective treatment for patients with a benign-malignant borderline lesion of the major duodenal papilla. This method also has an important clinical impact because it provides an accurate diagnosis, aids in the selection of an appropriate treatment strategy, and reduces unnecessary surgery.

Preoperative biliary drainage for hilar cholangiocarcinoma.

Hilar cholangiocarcinomas grow slowly, and metastases occur late in the natural history. Surgical cure and long-term survival have been demonstrated, when resection margins are clear. Preoperative biliary drainage has been proposed as a way to improve liver function before surgery, and to reduce post-surgical complications. Percutaneous transhepatic biliary drainage (PTBD) with multiple drains was previously the preferred method for the preoperative relief of obstructive jaundice. However, the introduction of percutaneous transhepatic portal vein embolization (PTPE) and wider resection has changed preoperative drainage strategies. Drainage is currently performed only for liver lobes that will remain after resection, and for areas of segmental cholangitis. Endoscopic biliary drainage (EBD) is less invasive than PTBD. Among EBD techniques, endoscopic nasobiliary drainage (ENBD) is preferable to endoscopic biliary stenting (EBS), because secondary cholangitis (due to the retrograde flow of duodenal fluid into the biliary tree) does not occur. ENBD needs to be converted to PTBD in patients with segmental cholangitis, those with a prolonged need for drainage, or when the extent of longitudinal tumor extension is not sufficiently well characterized.