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.

Antitumor effect of VEGFR2-targeted microbubble destruction with gemcitabine using an endoscopic ultrasound probe: In vivo mouse pancreatic ductal adenocarcinoma model.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) induces cellular inflow of drugs at low intensity, while high intensity eradicates tumor vessels. Since vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in pancreatic ductal adenocarcinoma (PDAC), VEGFR2-targeted microbubble (MB) might additionally increase the tissue specificity of drugs and thus improve antitumor effects. In addition, fixing the dual pulse intensity could maximize MB properties. This study evaluated the one-off (experiment 1) and cumulative (experiment 2) treatment effect of UTMD by regulating the dual pulse output applied to PDAC using VEGFR2-targeted MB. METHODS: C57BL/6 mice inoculated with Pan-02 cells were allocated to five groups: VEGFR2-targeted MB+ gemcitabine (GEM), VEGFR2-targeted MB, non-targeted MB+GEM, GEM, and control groups. After injection of GEM or GEM and either VEGFR2-targeted or non-targeted MB, UTMD was applied for several minutes at low intensity followed by high intensity application. In experiment 1, mice were treated by the protocol described above and then euthanized immediately or at the tumor diameter doubling time (TDT). In experiment 2, the same protocol was repeated weekly and mice were euthanized at TDT regardless of protocol completion. Histological analysis by CD31 and VEGFR2 staining provided microvascular density (MVD) and VEGFR2 expression along vessels (VEGFR2v) or intra/peripheral cells (VEGFR2c). RESULTS: In experiment 1, TDT was significantly longer in the VEGFR2-targeted MB+GEM group compared to the non-targeted MB+GEM, GEM, and control groups, while the VEGFR2-targeted MB group showed no statistical significance. MVD and VEGFR2v in the immediate euthanasia was significantly lower in the VEGFR2-targeted MB+GEM and VEGFR2-targeted MB groups than other conditions. In experiment 2, the VEGFR2-targeted MB+GEM group produced significantly longer TDT than the GEM or control groups, whereas the VEGFR2-targeted MB group showed no significant difference. Histology revealed significantly reduced VEGFR2v and VEGFR2c in the VEGFR2-targeted and non-targeted MB+GEM groups, while only VEGFR2v was significantly less in the VEGFR2-targeted MB group. CONCLUSIONS: UTMD-mediated GEM therapy with the dual pulse application using VEGFR2-targeted MB substantially suppresses PDCA growth.

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.

Novel quantitative analysis of the S100P protein combined with endoscopic ultrasound-guided fine needle aspiration cytology in the diagnosis of pancreatic adenocarcinoma.

Specimens obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) are often tiny and fragmented leading to an inconclusive and doubtful diagnosis. To overcome the limitations of EUS-FNA in the cytological diagnosis of pancreatic adenocarcinoma (PCA), we evaluated whether quantification of the S100P protein combined with EUS-FNA reliably discriminated between PCA and benign pancreatic lesions (BPL). A high sensitivity sandwich ELISA for S100P protein was developed to aid in the detection of PCA in small samples obtained using EUS-FNA. After experimental verification of the sandwich ELISA with cell lines and mouse xenograft tumors, 27 consecutive patients with suspicious PCA who underwent EUS-FNA were enrolled in the present study examining the combination of S100P protein assessment and EUS-FNA cytology. The concentration of the S100P protein in EUS-FNA samples from the PCA group was significantly higher than that in the BPL group (P=0.04). Using receiver operating characteristic curve analysis, we determined the S100P protein cut-off value for PCA diagnosis to be 99.8 ng/ml. The S100P protein levels combined with EUS-FNA cytology to detect PCA showed the following diagnostic values: sensitivity, 94.4% [95% confidence interval (CI), 75.7-99.1%]; specificity, 88.9% (95% CI, 51.8-99.7%); positive predictive value, 94.4% (95% CI, 72.7-99.9%); negative predictive value, 88.9% (95% CI, 51.8-99.7%); accuracy, 92.6% (95% CI, 75.7­99.1%); and area under the curve, 0.92 (95% CI, 0.79-1.00). We established a novel quantitative analysis for the S100P protein in EUS-FNA samples which, when combined with EUS-FNA cytology, could provide promising results for the reliable diagnosis of PCA.

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.