Shuhei Kawahata

Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction.

BACKGROUND AND STUDY AIMS Endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) has gained popularity as an alternative to percutaneous biliary drainage for patients in whom endoscopic retrograde cholangiopancreatography has failed. There are no previous studies comparing EUS-CDS with endoscopic transpapillary stenting (ETS) as first-line treatment for distal malignant obstruction. The aim of this study was to compare the clinical efficacy and safety of EUS-CDS and ETS as first-line treatment in patients with distal malignant biliary obstruction. PATIENTS AND METHODS A total of 82 patients with distal malignant biliary obstruction underwent initial biliary drainage using self-expandable metal stents at a tertiary care university hospital. ETS was performed between June 2009 and May 2012, and EUS-CDS was performed between May 2012 and March 2014. Clinical success rates, adverse event rates, and reintervention rates were retrospectively evaluated for EUS-CDS and ETS. RESULTS A total of 26 patients underwent EUS-CDS and 56 underwent ETS. Clinical success rates were equivalent between the groups (EUS-CDS 96.2 %, ETS 98.2 %; P = 0.54). The mean procedure time was significantly shorter with EUS-CDS than with ETS (19.7 vs. 30.2 minutes; P < 0.01). The rate of overall adverse events was not significantly different between the groups (EUS-CDS 26.9 %, ETS 35.7 %; P = 0.46). Post-procedural pancreatitis was only observed in the ETS group (0 % vs. 16.1 %; P = 0.03). The reintervention rate at 1 year was 16.6 % and 13.6 % for EUS-CDS and ETS, respectively (P = 0.50). CONCLUSIONS EUS-CDS performed by expert endoscopists was associated with a short procedure time and no risk of pancreatitis, and would therefore be feasible as a first-line treatment for patients with distal malignant biliary obstruction.

Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer

Background:Pancreatic ductal carcinoma (PDC) is one of the most lethal human carcinomas. Expression patterns of some genes may predict gemcitabine (GEM) treatment efficacy. We examined predictive indicators of survival in GEM-treated patients by quantifying the expression of several genes in pre-treatment endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) samples from patients with PDC.Methods:The expressions of human equilibrative nucleoside transporter 1 (hENT1), deoxycitidine kinase, ribonucleoside reductase 1, ribonucleoside reductase 2 and Notch3 in EUS-FNA tissue samples from 71 patients with unresectable PDC were quantified using real-time reverse transcription–polymerase chain reactions and examined for correlations with GEM sensitivity.Results:The log-rank test detected no significant differences in overall survival between GEM-treated patients with low and high mRNA levels of all genes examined. However, low Notch3 mRNA expression was significantly associated with longer overall survival in a multivariate analysis for survival (P=0.0094). High hENT1 expression level was significantly associated with a longer time to progression (P=0.039). Interaction tests for GEM administration and hENT1 or Notch3 mRNA expression were statistically significant (P=0.0054 and 0.0047, respectively).Conclusion:hENT1 and Notch3 mRNA expressions in EUS-FNA specimens were the key predictive biomarkers of GEM effect and GEM sensitivity in patients with unresectable PDC.

Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance

AIM To evaluate the safety and diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in a cohort of pancreatic cancer patients. METHODS Of 213 patients with pancreatic cancer evaluated between April 2007 and August 2011, 82 were thought to have resectable pancreatic cancer on the basis of cross-sectional imaging findings. Of these, 54 underwent EUS-FNA before surgery (FNA+ group) and 28 underwent surgery without preoperative EUS-FNA (FNA- group). RESULTS All 54 lesions were visible on EUS, and all 54 attempts at FNA were technically successful. The diagnostic accuracy according to cytology and histology findings was 98.1% (53/54) and 77.8% (42/54), respectively, and the total accuracy was 98.1% (53/54). One patient developed mild pancreatitis after EUS-FNA but was successfully treated by conservative therapy. No severe complications occurred after EUS-FNA. In the FNA+ and FNA- groups, the median relapse-free survival (RFS) was 742 and 265 d, respectively (P = 0.0099), and the median overall survival (OS) was 1042 and 557 d, respectively (P = 0.0071). RFS and OS were therefore not inferior in the FNA+ group. These data indicate that the use of EUS-FNA did not influence RFS or OS, nor did it increase the risk of peritoneal recurrence. CONCLUSION In patients with resectable pancreatic cancer, preoperative EUS-FNA is a safe and accurate diagnostic method.

Transpapillary dilation of refractory severe biliary stricture or main pancreatic duct by using a wire-guided diathermic dilator (with video)

Benign and malignant tumors generally cause strictures in the bile duct (BD) or the pancreatic duct (PD) and result in jaundice or abdominal pain. An appropriate technique for dilation of these strictures is therefore necessary. Endoscopic stent placement has been reported to improve the severity of abdominal pain in selected patients with benign and malignant BD and PD strictures. 1 During ERCP, a guidewire is passed through the stricture into the proximal BD or PD. Subsequently, a plastic stent(s) or self-expandable metallic stent is placed at the stricture. Although these stents are sometimes placed after dilation of the stricture, dilation may be unnecessary in most cases. Severe ductal strictures can usually be dilated using balloon dilation or a dilation catheter. However, this type of dilation is not possible when the BD or PD stricture is severe; in such refractory cases, only the guidewire can pass through it, and a screw drill may be used. 2,3 Several investigators have described the dissection of difficult PD strictures using a needle-knife or wire-guided snare forceps. 4-6 Diathermic dilators, which are commonly used for pancreatic fluid collection drainage, are effective for creating and enlarging the fistula channels between the stomach or duodenum and a pancreatic pseudocyst, PD, or gallbladder. 7,8 We recently reported our experience using a diathermic dilator to treat severe BD strictures. 9 The current prospective observational cohort study was conducted to evaluate whether a wire-guided diathermic dilator could pass through BD or PD strictures. We also evaluated the rate of adverse events after diathermic dilation of BD or PD strictures.

Smoking, family history of cancer, and diabetes mellitus are associated with the age of onset of pancreatic cancer in Japanese patients.

Objectives The aim of this study was to examine the association of risk factors including diabetes mellitus (DM) with the age of onset in Japanese pancreatic cancer (PC) patients. Methods We retrospectively reviewed 688 PC patients diagnosed at our institute. We analyzed the association between the age of onset of PC and the following variables: sex, smoking, alcohol, DM, and a family history of cancer especially PC. Results The mean age of PC diagnosis was 67.6 years. The onset of PC occurred earlier in current smokers (63.6 years old, P < 0.001) compared with past smokers (69.5 years old) and never smokers (68.6 years old). Patients with long-standing DM (>2 years) were older (70.5 years, P < 0.001) when diagnosed with PC than patients with new-onset DM (within 2 years) (66.9 years old) and patients without DM (66.7 years old). In the multivariate analysis, current smokers and a family history of cancer other than PC were associated with earlier onset. Conversely, long-standing DM was associated with later onset. Conclusions In Japanese PC patients, current smokers and a family history of cancer other than PC were associated with a younger age of onset. Conversely, long-standing DM was associated with a later onset.

Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer

BACKGROUND Irinotecan, oxaliplatin and leucovorin-modulated fluorouracil (FOLFIRINOX) and the combination regimen of gemcitabine and nanoparticle albumin-bound paclitaxel (GnP) (nab-PTX) improve the prognosis of patients with metastatic pancreatic cancer. However, no study has compared the efficacy of the two regimens. We compared retrospectively the efficacy and safety of the two regimens in patients with unresectable pancreatic cancer. METHODS Thirty-eight patients with unresectable locally advanced or metastatic pancreatic cancer received FOLFIRINOX or GnP as first-line chemotherapy between December 2013 and September 2015. In the FOLFIRINOX group, patients received 85 mg/m2 oxaliplatin followed by 180 mg/m2 irinotecan and 200 mg/m2 L-leucovorin, and by 400 mg/m2 fluorouracil as a bolus and 2,400 mg/m2 fluorouracil as a 46-h continuous infusion every 14 days. In the GnP group, patients received 125 mg/m2 nab-PTX followed by 1 g/m2, and gemcitabine on days 1, 8 and 15, repeated every 28 days. RESULTS Response rate was 6.3% in the FOLFIRINOX group and 40.9% in the GnP group (P=0.025). Median progression-free survival (PFS) was 3.7 months [95% confidence interval (CI), 3.0-4.5] in the FOLFIRINOX group and 6.5 months (95% CI, 6.2-6.9 months) in the GnP group (P=0.031). Drug toxicity in the GnP group was less than in the FOLFIRINOX group. CONCLUSIONS Efficacy and safety of GnP compare favorably to those of FOLFIRINOX in patients with pancreatic cancer. Additional prospective trials are warranted.

Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method

Endoscopic double self‐expandable metallic stent (SEMS) placement by the partial stent‐in‐stent (PSIS) method has been reported to be useful for the management of unresectable hilar malignant biliary obstruction. However, it is technically challenging, and the optimal SEMS for the procedure remains unknown. The aim of this study was to identify the risk factors for technical failure of endoscopic double SEMS placement for unresectable malignant hilar biliary obstruction (MHBO).

Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction : a feasibility study

Bilateral self‐expandable metallic stent (SEMS) placement for the management of unresectable malignant hilar biliary obstruction (UMHBO) is technically challenging to perform using the existing metallic stents with thick delivery systems. The recently developed 6‐Fr delivery systems could facilitate a single‐step simultaneous side‐by‐side placement through the accessory channel of the duodenoscope. The aim of this study was to evaluate the feasibility of this procedure.

Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.

AIM To identify the most effective endoscopic biliary drainage technique for patients with hilar cholangiocarcinoma. METHODS In total, 118 patients with hilar cholangiocarcinoma underwent endoscopic management [endoscopic nasobiliary drainage (ENBD) or endoscopic biliary stenting] as a temporary drainage in our institution between 2009 and 2014. We retrospectively evaluated all complications from initial endoscopic drainage to surgery or palliative treatment. The risk factors for biliary reintervention, post-endoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis, and percutaneous transhepatic biliary drainage (PTBD) were also analyzed using patient- and procedure-related characteristics. The risk factors for bilateral drainage were examined in a subgroup analysis of patients who underwent initial unilateral drainage. RESULTS In total, 137 complications were observed in 92 (78%) patients. Biliary reintervention was required in 83 (70%) patients. ENBD was significantly associated with a low risk of biliary reintervention [odds ratio (OR) = 0.26, 95%CI: 0.08-0.76, P = 0.012]. Post-ERCP pancreatitis was observed in 19 (16%) patients. An absence of endoscopic sphincterotomy was significantly associated with post-ERCP pancreatitis (OR = 3.46, 95%CI: 1.19-10.87, P = 0.023). PTBD was required in 16 (14%) patients, and Bismuth type III or IV cholangiocarcinoma was a significant risk factor (OR = 7.88, 95%CI: 1.33-155.0, P = 0.010). Of 102 patients with initial unilateral drainage, 49 (48%) required bilateral drainage. Endoscopic sphincterotomy (OR = 3.24, 95%CI: 1.27-8.78, P = 0.004) and Bismuth II, III, or IV cholangiocarcinoma (OR = 34.69, 95%CI: 4.88-736.7, P < 0.001) were significant risk factors for bilateral drainage. CONCLUSION The endoscopic management of hilar cholangiocarcinoma is challenging. ENBD should be selected as a temporary drainage method because of its low risk of complications.

Safety and Utility of Single-Session Endoscopic Ultrasonography and Endoscopic Retrograde Cholangiopancreatography for the Evaluation of Pancreatobiliary Diseases

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are essential for diagnosing and treating pancreatobiliary diseases. Single-session EUS and ERCP are considered to be essential in reducing the duration of hospital stays; however, complications are a primary concern. The aim of this study was to evaluate the safety and efficacy of single-session EUS and ERCP. Sixty-eight patients underwent single-session EUS and ERCP at a tertiary referral center between June 2008 and December 2012. We retrospectively reviewed patient data from a prospectively maintained EUS-ERCP database and evaluated the procedural characteristics and complications. Thirty-eight patients (56%) underwent diagnostic EUS, and 30 patients (44%) underwent EUS fine-needle aspiration, which had an overall accuracy of 100%. Sixty patients (89%) underwent therapeutic ERCP, whereas the remaining eight procedures were diagnostic. Thirteen patients underwent biliary stone extraction, and 48 underwent biliary drainage. The median total procedural time was 75 minutes. Complications were observed in seven patients (10%). Six complications were post-ERCP pancreatitis, which were resolved using conservative management. One patient developed Mallory-Weiss syndrome, which required endoscopic hemostasis. No sedation-related cardiopulmonary complications were observed. Single-session EUS and ERCP provided accurate diagnosis and effective management with a minimal complication rate.