Safety of skipping the tract dilation step for EUS-guided biliary drainage in patients with unresectable malignant biliary obstruction (with video).

BACKGROUND: Thin delivery system stents can be inserted directly without the need for a tract dilation step and are expected to reduce bile leakage during endoscopic ultrasound-guided biliary drainage (EUS-BD). The present study retrospectively compared the safety and efficacy of EUS-BD using a thin metal stent (< 7.5 Fr) with those of EUS-BD using a conventional stent (≥ 7.5 Fr). METHODS: The present study enrolled 112 patients who underwent EUS-BD using metal stents for unresectable malignant biliary obstruction between April 2016 and July 2022. The primary endpoint was the rate of adverse events (AEs). The secondary endpoints were clinical success rate, procedure time, procedure success rate in the absence of the tract dilation step, recurrent biliary obstruction rate, time to biliary obstruction, and overall survival. Risk factors associated with early AEs were also evaluated. RESULTS: The rate of early AEs was significantly lower (12% vs. 35%, P = 0.013) and the procedure success without the tract dilation step was significantly higher (82% vs. 33%, P < 0.001) in the thin than in the conventional delivery system stent group. None of the other secondary endpoints differed significantly between the two groups. Multivariate analysis showed that employing the tract dilation step during EUS-BD was a significant independent risk factor for early AEs (skipping vs. employing; HR, 9.66; 95% CI, 1.13-83.0, P = 0.028). CONCLUSION: Employing the tract dilation step during EUS-BD was a significant risk factor for early AEs. Metal stents with a delivery diameter < 7.5 Fr can be inserted directly without the tract dilation step, resulting in lower early AE rates.

Impact of sarcopenia on recurrent biliary obstruction after EUS-guided biliary drainage in patients with malignant biliary obstruction.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. The aim of this study was to assess the ability of sarcopenia to predict recurrent biliary obstruction (RBO) in patients with unresectable cancer after EUS-guided biliary drainage (EUS-BD). METHODS: The study enrolled 113 patients who underwent EUS-BD using the self-expandable metal stent (SEMS) for unresectable malignant biliary obstruction (MBO) between April 2016 and December 2021 at Wakayama Medical University Hospital. The skeletal muscle index at the third lumbar spine level (L3) was calculated from computed tomography images. We analyzed the cumulative incidence of RBO at 180 days after stent insertion. Univariate and multivariate analyses were performed to identify variables significantly associated with RBO. RESULTS: Seventy-six patients were assigned to the sarcopenia group, and 37 were assigned to the non-sarcopenia group. The 180-day cumulative incidence of RBO was 11% in the non-sarcopenia group and 29% in the sarcopenia group (p = 0.034). The time to RBO was significantly shorter for the sarcopenia group (p = 0.028; Gray's test). Multivariate analyses identified sarcopenia as an independent prognostic factor for RBO (present vs absent; HR 4.61; 95% CI 1.76-12.10, p = 0.001). The rates of biliary sludge/food impaction were significantly higher in the sarcopenia group for the causes of RBO (p = 0.048). There were no significant differences between the sarcopenia and the non-sarcopenia groups with respect to related EUS-BD adverse events. CONCLUSION: Sarcopenia is an independent indicator of RBO in patients with MBO who receive EUS-BD with SEMS.

Adverse events of self-expandable metal stent placement for malignant distal biliary obstruction: a large multicenter study.

BACKGROUND AND AIMS: Endoscopic placement of self-expandable metal stents (SEMSs) for malignant distal biliary obstruction (MDBO) may be accompanied by several types of adverse events. The present study analyzed the adverse events occurring after SEMS placement for MDBO. METHODS: The present study retrospectively investigated the incidence and types of adverse events in patients who underwent SEMS placement for MDBO between April 2018 and March 2021 at 26 hospitals. Risk factors for acute pancreatitis, cholecystitis, and recurrent biliary obstruction (RBO) were evaluated by univariate and multivariate analyses. RESULTS: Of the 1425 patients implanted with SEMSs for MDBO, 228 (16.0%) and 393 (27.6%) experienced early adverse events and RBO, respectively. Pancreatic duct without tumor involvement (P = .023), intact papilla (P = .025), and SEMS placement across the papilla (P = .037) were independent risk factors for acute pancreatitis. Tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis (P < .001). Use of fully and partially covered SEMSs was an independent risk factor for food impaction and/or sludge. Use of fully covered SEMSs was an independent risk factor for stent migration. Use of uncovered SEMSs and laser-cut SEMSs was an independent risk factor for tumor ingrowth. CONCLUSIONS: Pancreatic duct without tumor involvement, intact papilla, and SEMS placement across the papilla were independent risk factors for acute pancreatitis, and tumor involvement in the orifice of the cystic duct was an independent risk factor for cholecystitis. The risk factors for food impaction and/or sludge, stent migration, and tumor ingrowth differed among types of SEMSs.

Contrast-Enhanced Harmonic Endoscopic Ultrasound for Diagnosis of the Aggressiveness of Pancreatic Neuroendocrine Neoplasm.

The purpose of this study is to clarify the associations between the enhancement patterns on contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and the aggressiveness and prognosis of pancreatic neuroendocrine neoplasms (PanNENs). Patients who underwent CH-EUS and were pathologically diagnosed with PanNEN were included in this study. Patients were divided into three groups according to contrast-enhancement patterns on early-phase and late-phase imaging: "Group A", vascular rich in both phases; "Group B", vascular rich and vascular poor in early and late phases, respectively; "Group C", vascular poor in both phases. Of 39 patients, 25 were assigned to Group A, 7 to Group B, and 7 to Group C. The median overall survival was not reached in Groups A and B and was 335 days in Group C (p < 0.001). The 1-year survival rates were 100% in Group A, 60% in Group B, and 43% in Group C. Patients in Group C showed the shortest overall survival among the three groups. The vascular-poor pattern on late-phase CH-EUS had the highest sensitivity, specificity, and accuracy for aggressive PanNENs among the patterns analyzed on CH-EUS and CECT (84.6%, 91.7%, and 89.2%, respectively). CH-EUS is useful for the diagnosis of and predicting the prognosis of PanNENs.

Contrast-enhanced harmonic endoscopic ultrasonography for predicting the efficacy of first-line gemcitabine and nab-paclitaxel chemotherapy in pancreatic cancer.

BACKGROUND AND AIMS: The purpose of this study was to assess prognosis with different intratumoral vascularity on contrast-enhanced endoscopic harmonic ultrasonography (CH-EUS) in pancreatic cancer patients receiving chemotherapy. METHODS: Patients with unresectable pancreatic cancer who underwent CH-EUS before first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX) therapy were classified into four groups according to vascularity on the early and late phases of contrast enhancement: "Group A″, poor on both phases; "Group B″, rich and poor on the early and late phases, respectively; "Group C″, poor and rich on the early and late phases; "Group D″, rich on both phases. Subgroups were compared in terms of progression-free survival (PFS) and overall survival (OS). We also assessed whether the results with CH-EUS correlate with those of contrast-enhanced computed tomography (CE-CT). RESULTS: On CH-EUS, 57, 64, 0, and 24 patients were classified into Groups A, B, C, and D, respectively. The median PFS of patients in groups A, B, and D was 3.9, 7.6, and 10.8 months, respectively, and the median OS were 9.5, 13.1, and 18.6 months, respectively. Both PFS and OS were longest in Group D (p < 0.001 and p < 0.001, respectively). The results of CE-CT were consistent with those of CH-EUS, and there was a correlation between CE-CT and CH-EUS. CONCLUSIONS: Evaluation of intratumoral vascularity by CH-EUS may be useful for predicting the efficacy of chemotherapy in patients with pancreatic cancer. A better response to GEM and nab-PTX can be expected in patients showing rich vascularity at both the early and late phases.

Kras Gene Analysis Using Liquid-Based Cytology Specimens Predicts Therapeutic Responses and Prognosis in Patients with Pancreatic Cancer.

BACKGROUND: Although several molecular analyses have shown that the Kras gene status is related to long-term survival of patients with pancreatic ductal adenocarcinoma (PDAC), the results remain controversial. Here, we examined the Kras gene status in a cohort of unresectable PDAC patients who underwent first-line therapy with gemcitabine and nab-paclitaxel (GA) and assessed differences in chemotherapy responses and survival. METHODS: Patients with a histological diagnosis of PDAC (based on EUS-guided fine-needle aspiration) from 2017 to 2019 were enrolled. Tumor genomic DNA was extracted from residual liquid-based cytology specimens and Kras mutations were assessed using the quenching probe method. The relationships between the Kras status and progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: Of the 110 patients analyzed, 15 had wild-type Kras. Those with the wild-type gene showed significantly longer PFS and OS than those with mutant Kras (6.9/5.3 months (p = 0.044) vs. 19.9/11.8 months (p = 0.037), respectively). Multivariate analyses identified wild-type Kras as a significant independent factor associated with longer PFS and OS (HR = 0.53 (p = 0.045) and HR = 0.35 (p = 0.007), respectively). CONCLUSIONS: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.

Impact of sarcopenia on prediction of progression-free survival and overall survival of patients with pancreatic ductal adenocarcinoma receiving first-line gemcitabine and nab-paclitaxel chemotherapy.

BACKGROUND AND AIMS: Sarcopenia is an important prognostic factor for cancer patients. Here, we assessed the effects of sarcopenia on progression-free survival (PFS) and overall survival (OS) of patients with pancreatic ductal adenocarcinoma (PDAC) who underwent treatment with first-line gemcitabine and nab-paclitaxel (GEM and nab-PTX). METHODS: The study enrolled patients with unresectable PDAC who underwent chemotherapy between April 2016 and May 2020. The skeletal muscle index (SMI) at the third lumbar spine level (L3) was calculated from computed tomography (CT) images. Propensity score analysis was used to compare PFS and OS in the sarcopenia and non-sarcopenia groups. Univariate and multivariate analyses were performed to determine variables significantly associated with prognosis. RESULTS: Of the 176 patients who received first-line GEM and nab-PTX, 84 were selected and divided into two groups of 42 (the sarcopenia and the non-sarcopenia groups) by propensity score matching. The median PFS of the sarcopenia and the non-sarcopenia groups was 5.0 and 8.0 months, respectively (p = 0.004). The median OS was 10.3 and 18.1 months, respectively (p = 0.001). Multivariate analyses revealed that sarcopenia was an independent prognostic factor for PFS and OS (p = 0.004, p = 0.001, respectively). The rates of major grade 3 or 4 AEs were significantly higher in the sarcopenia group (p = 0.008). CONCLUSIONS: Sarcopenia is an independent indicator of a poor prognosis in patients with PDAC treated with first-line GEM and nab-PTX.

Value of contrast-enhanced harmonic endoscopic ultrasound for diagnosing hepatic metastases of pancreatic cancer: A prospective study.

BACKGROUND AND AIMS: This study aimed to compare contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) with fundamental B-mode endoscopic ultrasonography (EUS) and contrast-enhanced computed tomography (CE-CT) for the diagnosis of left hepatic lobe metastases of pancreatic adenocarcinoma. METHODS: In this single-center prospective study, CE-CT, EUS, and CH-EUS were performed to detect left hepatic lobe metastases in patients with pancreatic adenocarcinoma, and the detection rates were compared between EUS plus CH-EUS and the other two modalities. Subgroup comparisons of between-modality detection rate were performed in patients with only metastases of <10 mm. The number of pancreatic adenocarcinoma patients whose clinical stage and treatment strategy were changed because of EUS plus CH-EUS findings was also assessed. RESULTS: Thirty-one patients were diagnosed with left hepatic lobe metastases. For overall detection of left hepatic lobe metastases, EUS plus CH-EUS had significantly higher accuracy (94.3%) than CE-CT (86.7%) and EUS alone (87.6%) (P = 0.021 and P = 0.020, respectively). For detection of left hepatic lobe metastases < 10 mm, EUS plus CH-EUS (93.3%) was significantly superior to CE-CT (84.4%) and EUS alone (85.6%) (P = 0.021 and P = 0.020, respectively). In five of the 11 patients in whom only CH-EUS allowed detection of hepatic metastases, the stage and/or treatment strategy of the pancreatic adenocarcinoma was changed after CH-EUS. CONCLUSION: This study demonstrated that EUS plus CH-EUS has advantages over CE-CT and EUS alone with regard to the accuracy of detecting left hepatic lobe metastases, particularly small hepatic metastases and accurate staging.

Computed tomography findings for predicting the future occurrence of pancreatic cancer: value of pancreatic volumetry.

BACKGROUND: The features of pancreatic parenchyma that tend to progress towards pancreatic cancer (PC) are unknown. We performed volumetry of the pancreas in PC patients using computed tomography (CT) scans acquired before detection of PC, and investigated whether CT findings of pancreatic parenchyma could predict the future occurrence of PC. METHODS: Between April 2009 and March 2017, a total of 3769 patients underwent abdominal contrast-enhanced CT, the scans of which were archived as digital images. Among them, 15 PC patients underwent abdominal CT 6-120 months before diagnosis of PC. This retrospective study compared the 15 PC patients (PC group) with 15 propensity score-matched subjects without PC (non-PC group). Pancreatic volumetry and radiological findings were compared between the two groups. RESULTS: There were significant differences between the PC and non-PC groups in the volume of the main pancreatic duct (MPD) plus any cystic lesion (P = 0.007), volume of the MPD plus any cystic lesion/body surface area (BSA; P = 0.009), MPD diameter (P = 0.011), and MPD diameter/BSA (P = 0.013). Univariate analysis revealed volume of MPD plus any cystic lesion/BSA ≥ 0.53 mL/m2 (odds ratio [OR] 38.50, P = 0.002), volume of pancreatic parenchyma/BSA < 27.0 mL/m2 (OR 12.25, P = 0.030), and MPD diameter/BSA ≥ 1.0 mm/m2 (OR 13.00, P = 0.006) as significant risk factors for PC. CONCLUSIONS: Quantification of the volume of MPD plus any cystic lesion/BSA, volume of pancreatic parenchyma/BSA, and MPD diameter/BSA on pre-diagnosis CT were useful for predicting the future occurrence of PC.

Covered self-expandable metal stents versus plastic stents for preoperative biliary drainage in patient receiving neo-adjuvant chemotherapy for borderline resectable pancreatic cancer: Prospective randomized study.

OBJECTIVES: This single-center comparative randomized superiority study compared biliary stenting using fully covered self-expandable metal stents (FCSEMS) and biliary stenting using plastic stents (PS) in preoperative biliary drainage of patients with borderline resectable pancreatic cancer (BRPC) who are planned to undergo a single regimen of neo-adjuvant chemotherapy (NAC). METHODS: Twenty-two patients with BRPC who required preoperative biliary drainage before NAC (Gemcitabine plus Nab-paclitaxel) were randomly assigned 1:1 to the FCSEMS or PS group. The primary endpoint was the rate of stent dysfunction until surgery or tumor progression. Secondary endpoints were stent patency, number of re-interventions, adverse events of endoscopic retrograde biliary drainage (EBD), operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs. RESULTS: Eleven patients in each of the groups reached the primary endpoint. The FCSEMS group showed a significantly lower rate of stent dysfunction (18.2% vs. 72.8%, P = 0.015), longer stent patency (P = 0.02), and lower number of re-interventions for stent dysfunction (0.27 ± 0.65 vs. 1.27 ± 1.1, P = 0.001) than the PS group. The adverse events of EBD, operation time, volume of intraoperative bleeding, postoperative hospitalization, postoperative adverse events and medical costs did not significantly differ between the two groups. CONCLUSIONS: In patients with BRPC for preoperative biliary drainage, stent dysfunction occurred less frequently with FCSEMSs than with PSs. In addition, FCSEMS and PS provided similar preoperative management of BRPC in terms of the safety of surgery and medical costs. (UMIN ID000030473).