Potential significance of uncovered self-expandable metal stents for distal malignant biliary obstruction: A propensity score-adjusted competing risk regression analysis.

Objectives: Selection criteria for self-expandable metal stents (SEMSs) with or without cover during palliative treatment of distal malignant biliary obstruction (DMBO) remain unclear. We evaluated factors associated with time to recurrent biliary obstruction (TRBO) in fully covered SEMSs (FCSEMSs) and uncovered SEMSs (UCSEMSs). Methods: We retrospectively analyzed consecutive patients with DMBO who received a SEMS. TRBO was determined using the Kaplan-Meier analysis, and complications were compared between the FCSEMS and UCSEMS groups. After TRBO-associated factors were extracted using multivariate competing-risks regression (CRR), propensity score-adjusted CRRs were performed to verify their robustness. Results: There were 180 patients (66 FCSEMSs and 114 UCSEMSs) enrolled in this study. There was no significant difference between median TRBO in the FCSEMS and UCSEMS groups (275 vs. 255 days, p = 0.67). Complications were more frequent in the FCSEMS than UCSEMS group (21.2% vs. 8.8%; p = 0.023). Multivariate CRR for TRBO-associated factors revealed that "pancreatic ductal carcinoma (PDAC) treated with UCSEMS" was the only independent predictor of TRBO (p = 0.03). Similarly, the propensity score-adjusted CRRs showed no significant difference in TRBO in "FCSEMS" vs "UCSEMS" (p = 0.96); however, there was a significant difference in "PDAC using UCSEMS" vs "other" (p = 0.043). In the palliative care group including any DMBO without chemotherapy, the first quartile of the TRBO of UCSEMS was 100 days. Conclusions: UCSEMSs are a possible option for both patients with DMBO arising from PDAC and for patients with any DMBO receiving palliative care who should avoid SEMS-related complications.

Diagnostic Dilemma of Biliopancreatic Contrast-Enhanced Harmonic Endoscopic Ultrasonography.

Background: The utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) alone in the biliopancreatic region appears to be limited because it is highly dependent on the experience and skill of the endoscopist. Therefore, the present study aimed to validate the efficacy of CH-EUS in clinical practice. Methods: Between January 2018 and March 2019, 301 consecutive patients who underwent CH-EUS were prospectively enrolled in this study. The diagnostic performance of CH-EUS was compared with that of dynamic computed tomography (CT), magnetic resonance imaging (MRI), and all combinations (i.e., CH-EUS, dynamic CT, and MRI) using a Bonferroni correction. A multiple logistic regression analysis was performed to extract each disease that allowed the CH-EUS diagnosis to be consistent with the final diagnosis. Results: In multiple comparisons of diagnostic performance, no significant differences were observed among dynamic CT, MRI, and CH-EUS (p = 1.00), but the diagnostic performance was significantly higher when all modalities were combined (p < 0.001). Moreover, only intraductal papillary mucinous neoplasm comprising adenoma or carcinoma (IPMN, n = 161) showed significance with respect to the agreement with the final diagnosis (p = 0.006). Conclusions: Our results showed that CH-EUS-based diagnosis of IPMN may be possible in clinical practice. On the contrary, to accurately diagnose biliopancreatic diseases other than IPMN, comprehensive diagnosis using multiple modalities may be necessary, rather than relying on CH-EUS alone.

Endoscopic ultrasound-guided fine-needle biopsy histology with a 22-gauge Franseen needle and fine-needle aspiration liquid-based cytology with a conventional 25-gauge needle provide comparable diagnostic accuracy in solid pancreatic lesions.

BACKGROUND AND AIM: Fine-needle biopsy (FNB) needles obtain more core samples and support the shift from cytologic to histologic evaluation; however, recent studies have proposed a superior diagnostic potential for liquid-based cytology (LBC). This study compared the diagnostic ability of endoscopic ultrasound (EUS)-guided FNB histology with a 22-gauge Franseen needle (22G-FNB-H) and fine-needle aspiration (FNA) LBC with a conventional 25-gauge needle (25G-FNA-LBC). METHODS: We analyzed 46 patients who underwent both 22G-FNB-H and 25G-FNA-LBC in the same lesion during the same endoscopic procedure. This study evaluated the diagnostic ability of each needle, diagnostic concordance between needles, and incremental diagnostic effect of both needles compared to using each needle alone. RESULTS: The agreement rate for malignancy between both techniques was 93.5% (kappa value = 0.82). There was no significant difference in the diagnostic ability of both methods. 22G-FNB-H and 25G-FNA-LBC provided an incremental diagnostic accuracy in two (4.3%) cases and one (2.2%) case, respectively. CONCLUSION: Our study demonstrated that the diagnostic accuracy of 25G-FNA-LBC and 22G-FNA-H for solid pancreatic lesions were comparable. A conventional 25-gauge needle that punctures lesions with ease can be used in difficult cases and according to the skill of the endoscopist.

Best period to replace or change plastic stents with self-expandable metallic stents using multivariate competing risk regression analysis.

In endoscopic biliary drainage (EBD) for various benign and malignant biliary disorders, the appropriate timing to replace or change a plastic stent (PS) with a self-expandable metallic stent (SEMS) remains unclear. This study aimed to define the best period to replace or change a PS with a SEMS. Between January 1, 2012, and December 31, 2018, 1,887 consecutive EBD procedures, including 170 SEMS placements, were retrospectively identified. The period to recurrent biliary obstruction (PRBO) was estimated and compared between the malignant and benign groups and according to each disease using time to event analysis and competing risk analysis. Compared with the benign group, the malignant group had significantly shorter median PRBO with interquartile range (IQR) after PS placement [108 (39 - 270) vs. 613 (191 - 1,329) days, P < 0.001], even on multivariate analysis, with a subdistribution hazard ratio (SHR) of 3.58 (P < 0.001). The shortest PRBO distribution from the first quartile of the non-RBO period was seen in Mirizzi syndrome cases (25 days, P = 0.030, SHR = 3.32) in the benign group and in cases of pancreatic cancer (32 days, P = 0.041, SHR = 2.06); perihilar bile duct cancer (27 days, P = 0.006, SHR = 2.69); and ampullary cancer (22 days, P = 0.001, SHR = 3.78) in the malignant group. Our study supports that stent replacement for the benign group is feasible after 6 months, and the best period to replace or change a PS with a SEMS should be decided on the basis of the underlying disease to prevent RBO.

Use of modified U1 small nuclear RNA for rescue from exon 7 skipping caused by 5'-splice site mutation of human cathepsin A gene.

Cathepsin A (CTSA) is a multifunctional lysosomal enzyme, and its hereditary defect causes an autosomal recessive disorder called galactosialidosis. In a certain number of galactosialidosis patients, a base substitution from adenine to guanine is observed at the +3 position of the 7th intron (IVS7 +3a>g) of the CTSA gene. With this mutation, a splicing error occurs; and consequently mRNA lacking the 7th exon is produced. This skipping of exon 7 causes a frame shift of the transcripts, resulting in a non-functional CTSA protein and hence galactosialidosis. This mutation seems to make the interaction between the 5'-splice site of intron 7 of pre-mRNA and U1 small nuclear RNA (U1 snRNA) much weaker. In the present study, to produce properly spliced mRNA from the CTSA gene harboring this IVS7 +3a>g mutation, we examined the possible usefulness of modified U1 snRNA that could interact with the mutated 5'-splice site. Toward this goal, we first prepared a model system using a mutant CTSA mini gene plasmid for delivery into HeLa cells. Then, we examined the effectiveness of modified U1 snRNA on the formation of properly spliced mRNA from this mutant CTSA mini gene. As a result, we succeeded in obtaining improved formation of properly spliced CTSA mRNA. Our results suggest the usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene.

The Effectiveness and Feasibility of Endoscopic Ultrasound-guided Transgastric Drainage of Postoperative Fluid Collections Early After Pancreatic Surgery.

PURPOSES: To assess the feasibility and usefulness of endoscopic ultrasound-guided transgastric drainage (EUS-GD) in patients who required early postoperative drainage of peripancreatic fluid collection or postoperative pancreatic fistulas after pancreatic surgery. PATIENTS AND METHODS: Between May 2012 and January 2016, 33 patients who developed peripancreatic fluid collection or postoperative pancreatic fistulas after pancreatic resection underwent EUS-GD or percutaneous drainage (PTD). Outcomes were compared retrospectively. RESULTS: The drainage procedures were performed on postoperative day 4 to 71 (median, 12) in the EUS-GD group, and 7 to 35 (median, 14) in the PTD group. Technical and clinical success rates reached 92% (11/12) in the EUS-GD group, and 100% (21/21) in the PTD group with no complications or mortality. The duration of hospital stay after drainage was 10 to 44 (median, 15) days for EUS-GD, compared with 10 to 39 (median, 21) days for PTD. CONCLUSIONS: EUS-GD is a safe and useful method for early drainage, which could be a good alternative to PTD.

A novel second-generation multibending backward-oblique viewing duodenoscope in ERCP.

INTRODUCTION: Successful access to the papilla and cannulation of the desired duct can be technically challenging. A novel second-generation multi-bending backward-oblique viewing duodenoscope (2nd M-D scope) was developed to overcome this difficulty. The aim of the present study was to evaluate the utility of 2nd M-D scope during biliary ERCP. MATERIAL AND METHODS: This was a retrospective review of 53 patients with native papilla who underwent biliary ERCP with the 2nd M-D scope. RESULTS: Biliary cannulation and interventional procedures were successfully completed in all patients. In two of these patients, ERCP was initially attempted with a conventional single bending duodenoscope, but biliary cannulation was unsuccessful; one had Billroth-I gastrectomy, and the other had a Type III choledochal cyst. However, with the 2nd M-D scope, biliary cannulation and interventional procedures were successfully achieved. Finally, in nine patients, upward or downward angulation of the proximal bending portion in addition to the distal bending portion was used during ERCP, and the operator's comments demonstrated that it was helpful for obtaining an appropriate en face view to look up to the papilla and facilitate successful biliary cannulation. CONCLUSION: The newly developed 2nd M-D scope could safely facilitate biliary cannulation in selected patients during ERCP.

Contrast-enhanced harmonic endoscopic ultrasonography in the differential diagnosis of gallbladder wall thickening.

BACKGROUND AND AIMS: Differentiation of gallbladder (GB) carcinoma from benign GB wall thickening is challenging. The recent introduction of second-generation ultrasonic contrast agents has made contrast harmonic imaging with EUS possible. The aim of our study was to evaluate the utility of contrast-enhanced harmonic EUS (CH-EUS) for the differential diagnosis of GB wall thickening. METHODS: Thirty-six consecutive patients with GB wall thickening imaged by CH-EUS and then underwent surgery were enrolled in this study. After the lesions were observed with conventional harmonic EUS (H-EUS), CH-EUS was performed with intravenous injection of 0.015 ml/kg of Sonazoid. Three reviewers with various levels of experience of EUS (Reviewer A: experienced endosonographer, B: EUS trainee, C: experienced gastroenterologist with expertise in transabdominal ultrasound but no EUS experience) were blinded to findings of recorded video of H-EUS and CH-EUS. The diagnostic accuracy of H-EUS and CH-EUS for malignant GB wall thickening was compared. RESULTS: Final diagnoses based on surgical histology were GB carcinoma in 16, cholecystitis in 11, adenomyomatosis in 6 and cholesterolosis in 3. Overall sensitivity, specificity and accuracy for diagnosing malignant GB wall thickening of H-EUS and CH-EUS were 83.3 versus 89.6, 65 versus 98% (p < 0.001) and 73.1 versus 94.4% (p < 0.001). The inter-observer agreement for H-EUS was moderate (κ = 0.51), whereas that for CH-EUS was substantial (κ = 0.77). The inhomogeneous enhanced pattern on CH-EUS was a strong predictive factor of malignant GB wall thickening. CONCLUSION: CH-EUS has the potential to improve the preoperative diagnostic accuracy and inter-observer agreement in the differential diagnosis of GB wall thickening.

A comparison of electronic radial and curvilinear endoscopic ultrasonography in the detection of pancreatic malignant tumor.

OBJECTIVE: There is no comparative study of electronic radial endoscopic ultrasonography (ER-EUS) and electronic curvilinear EUS (EC-EUS). The aim of this study was to compare the accuracy of ER-EUS and EC-EUS for detecting pancreatic malignancies. METHODS: This was a retrospective review of the patients who had EUS assessment from September 2008 to December 2011 for suspicious pancreatic tumors. Sensitivity, specificity, and area under the ROC curve to detect pancreatic malignancies were calculated and compared between the ER-EUS and EC-EUS cohort. The final diagnosis of pancreatic malignancy was based on pathology, or the consensus of patient's clinical course and multimodal imaging tests. RESULTS: Two hundred twenty-one patients were included and divided into two cohorts: ER-EUS (n = 139) and EC-EUS (n = 82) cohorts. With propensity score matching method, 70 cases in each cohort were selected for the comparison. There was no significant difference in sensitivity, specificity, and area under the ROC curve to detect pancreatic malignancy between ER-EUS and EC-EUS cohort (88.5 vs. 100%, 88.6 vs. 90.9%, 0.8855 vs. 0.9545). CONCLUSION: ER-EUS and EC-EUS provided similar accuracy for the detection of pancreatic malignancies. In view of similar diagnostic results of ER-EUS and EC-EUS for the detection of pancreatic malignancy, and the advantage of being able to perform FNA with EC-EUS, EC-EUS may be the preferred choice.

EUS-guided rendezvous drainage for pancreatic duct obstruction from stenosis of pancreatojejunal anastomosis after pancreatoduodenostomy.

A 79-year-old man underwent pancreatoduodenectomy with Imanaga reconstruction for an ampullary adenocarcinoma in 2003. After that, he experienced recurrent pancreatitis with a suspicious stenotic pancreatojejunal anastomosis. Although endoscopic drainage through the pancreatojejunal anastomosis was attempted, the stenotic anastomosis could not be located endoscopically. Therefore, endosonography-guided rendezvous drainage through the anastomosis was performed, and endoscopic pancreatic stent placement was successfully completed. Thereafter, the patient did not experience any further attacks of pancreatitis. Endosonography-guided rendezvous drainage is a feasible treatment option for recurrent pancreatitis due to stenosis of pancreatojejunal anastomosis.

Novel quantitative perfusion analysis with contrast-enhanced harmonic EUS for differentiation of autoimmune pancreatitis from pancreatic carcinoma.

OBJECTIVE: Autoimmune pancreatitis (AIP) is often misdiagnosed as pancreatic carcinoma (PC) despite recent advances in imaging tests. The aim of the study was to evaluate whether the quantitative perfusion analysis using software "Time intensity curve" with contrast-enhanced harmonic EUS (CH-EUS) facilitate the differentiation of AIP from PC. METHODS: Consecutive patients with focal AIP and pancreatic carcinoma who underwent CH-EUS from January 2009 to September 2010 were analyzed. CH-EUS was performed with intravenous administration of an ultrasonographic contrast (Sonazoid) and electronic radial echoendoscope. The graph of time intensity curve (TIC) for pancreatic mass was generated to depict the changes in signal intensity over time within the region of interest (ROI). ROI was placed to cover an area with a pancreatic mass lesion. Based on the analysis of TIC, base intensity before injection (BI), peak intensity (PI), time to peak, and maximum intensity gain (MIG: PI-BI) were calculated. RESULTS: Eight patients with focal AIP and twenty-two patients with PC were evaluated by TIC. PI and MIG of mass lesion of AIP were significantly higher than that of PC (21.4 dB vs. 9.6 dB, 17.5 vs. 6.6). Receiver operating characteristics analysis yielded an optimal MIG cutoff value of 12.5 with high sensitivity and specificity. CONCLUSION: Pancreatic mass lesions of AIP and PC exhibited markedly different patterns with the TIC. This novel diagnostic modality using TIC generated by CH-EUS might offer an opportunity to improve accuracy in the differential diagnosis between pancreatic mass lesion of AIP and PC.

Diagnostic approach using endosonography guided fine needle aspiration for lymphadenopathy in primary sclerosing cholangitis.

We report a case of primary sclerosing cholangitis (PSC) with benign lymphadenopathy which was diagnosed with endosonography guided fine needle aspiration (EUS-FNA). A 65-year-old woman was admitted to Jikei University Hospital with severe jaundice. Although endoscopic retrograde cholangiography and liver biopsy revealed the findings consistent with PSC, abdominal computed tomography revealed numerous large perihepatic lymph nodes with a maximum diameter of more than 3 cm. Therefore, EUS-FNA was done in order to exclude malignant lymphadenopathy, and adequate specimens obtained by EUS-FNA showed reactive hyperplasia of lymph node. The patients were scheduled to undergo liver transplantation.