Trisectoral Metal Stenting Using Combined Stent-by-Stent and Stent-in-Stent Method for Malignant Hilar Biliary Obstruction: A Prospective Pilot Study.

BACKGROUND: Endoscopic trisectoral metal stent (MS) placement for malignant hilar biliary obstruction (MHBO) poses technical challenges, although it may prolong survival and stent patency. Combined stent-by-stent and stent-in-stent (SBSIS) methods can reduce technical difficulty. This study aimed to examine the use of the SBSIS in patients with Bismuth type III or IV MHBO. METHODS: This prospective pilot study enrolled 30 eligible patients between January 2020 and October 2022. The study outcomes included technical and clinical success, recurrent biliary obstruction (RBO), and adverse events (AE) besides RBO associated with SBSIS for MHBO. RESULTS: The technical success rate was 93.3% (28/30 patients). Clinical success was achieved in all patients with technical success. The early and late AEs rates were 6.7% (2/30) and 7.1% (2/28), respectively. The incidence of RBO was 35.7% (10/28). RBO was treated with an endoscopic transpapillary approach in eight patients and an endoscopic ultrasound-guided transmural approach in two patients. The median time to RBO was 162 days, and the median overall survival was 148 days. CONCLUSIONS: This first prospective study investigating the SBSIS method demonstrated good technical feasibility with a low AE rate. Therefore, it can be considered a better option when contemplating trisectoral MS placement for high-grade MHBO.

Prophylactic use of a self-assembling peptide hydrogel for preventing delayed bleeding after endoscopic sphincterotomy: A propensity score-matched analysis.

BACKGROUND AND AIM: Delayed endoscopic sphincterotomy-related bleeding (ES bleeding) is an unavoidable adverse event (AE) that can have serious ramifications. Intraoperative ES bleeding, which stops spontaneously in most cases, is a known risk factor for delayed bleeding. This study aimed to examine the preventive effect of a novel self-assembling peptide (SAP) for delayed ES bleeding in patients who attained spontaneous hemostasis after intraoperative ES bleeding. METHODS: A total of 1507 patients met the eligibility criteria for inclusion in this study. The rates of delayed ES bleeding and AE besides bleeding were compared between patients administered the SAP (SAP group) and those who were simply observed after spontaneous hemostasis of intraoperative ES bleeding (control group). Propensity score matching was performed to adjust for differences between the groups. RESULTS: The rate of delayed ES bleeding was significantly lower in the SAP group than that in the control group (0.9% vs 3.8%, P = 0.044). The rates of AEs other than bleeding were 2.4% and 3.8% in the SAP and control groups, respectively, and the difference lacked statistical significance (P = 0.481). Multivariate analysis revealed that the use of SAP was significantly associated with a lower frequency of delayed ES bleeding (odds ratio, 0.35; 95% confidence interval, 0.13-0.98; P = 0.047). CONCLUSIONS: Self-assembling peptide may be a simple, safe, and useful way to reduce the risk of delayed ES bleeding in patients who experienced intraoperative ES bleeding and obtained subsequent spontaneous hemostasis.

Endoscopic gallbladder inside-stenting combined with aspirated lavage for calculous cholecystitis in poor surgical candidates: a prospective pilot study.

Although long-term stent placement via endoscopic gallbladder stenting (EGBS) reportedly reduces cholecystitis recurrence in patients unfit to undergo cholecystectomy, it can increase the frequency of other late adverse events (AEs) such as cholangitis. This study aimed to examine the feasibility of endoscopic gallbladder inside-stenting (EGB-IS) with lavage and aspiration. This prospective, single-center, pilot study enrolled 83 patients with acute calculous cholecystitis who were poor candidates for surgery. A dedicated catheter with eight side holes was used for lavage and aspiration, and a dedicated single-pigtail stent equipped with a thread was used for EGB-IS. Outcomes such as technical success, clinical success, early AEs, recurrence of cholecystitis, and other symptomatic late AEs associated with EGB-IS with lavage and aspiration were evaluated. The technical and clinical success rates were 80.7% (67/83) and 98.5% (66/67), respectively. The rate of early AEs was 3.6% (3/83). The rate of recurrent cholecystitis was 4.5% (3/66) and that of symptomatic late AEs (besides cholecystitis) was 6.1% (4/66). Consequently, the rate of overall late AEs (cholecystitis plus other events) was 10.6% (7/66). The 1-, 2-, and 3-year cumulative incidence rates of all late AEs were 3.2%, 11.2%, and 18.9%, respectively. EGB-IS with lavage and aspiration for calculous cholecystitis showed promising results in poor surgical candidates. EGB-IS may be useful when EGBS with long-term stent placement is planned, since prevention of cholecystitis recurrence, without a rise in the incidence of other AEs, is anticipated.

Endoscopic Ultrasound-Guided Naso-gallbladder Drainage Using a Dedicated Catheter for Acute Cholecystitis After Transpapillary Metal Stent Placement for Malignant Biliary Obstruction.

BACKGROUND: Acute cholecystitis is a significant adverse event after self-expandable metal stent (SEMS) placement for malignant biliary obstruction (MBO); however, no appropriate treatment strategy has been established for its management. AIMS: This study aimed to examine the feasibility and utility of endoscopic ultrasound-guided naso-gallbladder drainage (EUS-NGBD) for the management of acute cholecystitis occurring after SEMS placement. METHODS: This retrospective study investigated consecutive patients with acute cholecystitis after SEMS placement for unresectable MBO, in whom EUS-NGBD was attempted. The study outcomes included technical success, clinical success, procedure time, adverse event, and cholecystitis recurrence, associated with the procedure. RESULTS: During the study period, EUS-NGBD was performed for SEMS-related acute cholecystitis in 30 patients with MBO. The technical and clinical success rates were 96.7% (29/30) and 96.6% (28/29), respectively. The median procedure time was 15 min, and rate of procedure-related adverse event was 3.3% (1/30). The median duration from the procedure to tube removal was 9 days. No adverse events were observed after removal. The median hospitalization duration after the procedure was 14 days, and the median duration to the (re-)start of chemotherapy from cholecystitis onset was 13 days. The median overall survival after EUS-NGBD was 123 days, and the rate of cholecystitis recurrence until death was 4.2% (1/28). CONCLUSIONS: This study demonstrated that EUS-NGBD possesses good technical and clinical feasibility with an acceptable adverse event rates and short hospitalization and chemotherapy withdrawal period. Therefore, EUS-NGBD may be a good option for the treatment of SEMS-related cholecystitis in patients with MBO.

Long-term disease control by endobiliary radiofrequency ablation in localized extrahepatic cholangiocarcinoma: a first case report.

An 84-year-old woman with cerebrovascular disease, dementia, and chronic kidney disease developed jaundice because of localized extrahepatic cholangiocarcinoma (eCCA) at the lower bile duct. Aggressive treatment, including surgery and chemotherapy, was difficult because of the underlying disease; therefore, only metal stent placement with endobiliary radiofrequency ablation (RFA) was performed. Subsequently, six additional RFA sessions were performed 12, 16, 24, 27, 33, and 36 months after the initial RFA using the same settings as the first RFA session. All these procedures were performed for tumor ingrowth. Computed tomography performed 42 months after the initial procedure revealed no stent with stricture resolution and no other metastatic lesion. Thereafter, no recurrence or adverse events have been observed with persisting stent-free status until the reporting of this study (72 months after the initial procedure). This is the first report of a stent-free status and long-term survival in a patient with localized eCCA that was achieved using only endobiliary RFA without any other anti-tumor treatment. Although several problems and issues associated with endobiliary RFA remain unelucidated, it may be a useful therapeutic option for early and localized eCCA in poor surgical candidates.

A novel controllable cannula with a short flexible tip for reintervention after stent-by-stent placement in malignant hilar biliary obstruction.

N/A.

Endoscopic biliary ethanol ablation using a novel multi-hole balloon catheter: In vivo feasibility study in a swine model.

BACKGROUND: Minimally invasive local treatment could be a good option for the treatment of extrahepatic cholangiocarcinoma (eCCA). This study aimed to evaluate the feasibility of a novel local treatment method, endoscopic biliary ethanol ablation (EA), in vivo using a swine model. METHODS: This study utilized a prototype of the newly developed multi-hole balloon catheter. The swine bile duct was ablated using this balloon via the same approach as the conventional endoscopic retrograde cholangiography procedure. The study outcomes included technical success, clinical success, and adverse events associated with endoscopic biliary EA. RESULTS: Fourteen miniature pigs underwent endoscopic biliary EA. Technical success was achieved for all endoscopic EA procedures without any hindrance. All pigs were reared and followed up for a median 35-day period after the procedure. No change was observed in the bile duct wall in one case, in which sufficient contact was not achieved between the balloon and bile duct wall. Except for this case, stricture formation occurred at the site of ablation, where the epithelium was sloughed and necrosis with denaturation replaced the granulation tissue and fibrotic changes. The median length and depth of the ablation area were 17.05 and 2.21 mm, respectively. No adverse events were observed, except for the formation of bile duct strictures and sequelae associated with strictures. CONCLUSIONS: This preliminary study was the first to report endoscopic biliary EA using a novel multi-hole balloon catheter, which demonstrated technical feasibility and potential for the treatment for eCCA.

Double bare metal stent deployment combined with intraductal radiofrequency ablation for malignant distal biliary obstruction: a prospective pilot study.

Although uncovered self-expandable metal stents (SEMSs) possess certain advantages such as averting cystic duct obstruction and stent migration, they are susceptible to ingrowth occlusion. The combination of the double bare stent (DBS) and endobiliary radiofrequency ablation (RFA) may reduce ingrowth. Hence, this study aimed to examine the utility of this method for the treatment of unresectable malignant distal biliary obstruction (MDBO). This prospective, single-center, pilot study enrolled 51 patients who met the eligibility criteria between February 2020 and January 2022. The study outcomes included technical success, clinical success, recurrent biliary obstruction (RBO), and other adverse events (AE) besides RBO associated with DBS placement with RFA for MDBO. The technical success rate was 98.0% (50/51). Clinical success was achieved in all patients in whom technical success was achieved. The rates of early and late AEs were 5.9% (3/51) and 8.0% (4/50), respectively. The incidence rate of RBO was 38.0% (19/50). Sludge occlusion, ingrowth occlusion, and overgrowth occlusion occurred in 26.0% (13/50), 8.0% (4/50), and 2.0% (1/50) of patients, respectively (the main cause of RBO was undeterminable in 1 patient). The median time to RBO was 241 days. DBS with RFA showed good technical feasibility, good long-term outcomes, acceptable AE rates, and most importantly, a low ingrowth occlusion rate when employed for the treatment of MDBO.

Endoscopic radiofrequency ablation for ingrowth occlusion after bilateral metal stent placement for malignant hilar biliary obstruction: a prospective pilot study.

BACKGROUND AND AIMS: Endoscopic biliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment; however, its utility remains uncertain. This study aimed to examine the feasibility of RFA for the palliation of ingrowth after bilateral SEMS placement in patients with malignant hilar biliary obstruction. METHODS: This prospective, single-center, pilot study enrolled 30 patients who met the eligibility criteria between April 2020 and March 2022. Study outcomes were technical success, clinical success, recurrent biliary obstruction (RBO), and adverse events (AEs) besides RBO associated with RFA for ingrowth occlusion. Furthermore, factors predictive of clinical success were evaluated. RESULTS: Technical and clinical success rates were 93.3% (28/30) and 71.4% (20/28), respectively. The rates of early and late AEs were 6.7% (2/30) and 10.0% (2/20), respectively. The incidence rate of RBO after RFA was 45.0% (9/20), and the median time to RBO was 163 days. Multivariate analysis of the factors affecting clinical success revealed a positive association between the recanalization diameter on the ingrown part within the SEMS (odds ratio, 1.13; 95% confidence interval, 1.01-1.26; P = .038). The calculated optimal cutoff for the ratio of the recanalization diameter to the SEMS diameter for predicting clinical success was 51.1%. CONCLUSIONS: Endoscopic biliary RFA elicited promising results, with good long-term stent patency and without the requirement of any additional stent placement, for the palliation of ingrowth occlusion after bilateral SEMS placement. However, the clinical success rate was insufficient, necessitating improvements in the future. (Clinical trial registration number: UMIN000040154.).

Endoscopic Ultrasound-Guided Hepaticogastrostomy with Antegrade Stenting Without Dilation Device Application for Malignant Distal Biliary Obstruction in Pancreatic Cancer.

BACKGROUND: Endoscopic ultrasound-guided hepaticogastrostomy with antegrade stenting (EUS-HGAS) is a promising therapeutic option for malignant distal biliary obstruction (MDBO) in the event of transpapillary approach failure. Eliminating the fistula dilation step may further decrease the incidence of adverse events (AE) and simplify the procedure. AIMS: This study focused on MDBO associated with pancreatic cancer and aimed to examine the utility of EUS-HGAS without the use of any dilation devices. METHODS: This retrospective study investigated consecutive patients in whom the transpapillary approach had failed or was difficult, and who underwent EUS-HGAS without dilation device usage, using a tapered small-diameter catheter, ultrathin delivery system, and tapered dedicated plastic stent. The outcomes of this study included the technical success, clinical success, AE incidence, and recurrent biliary obstruction (RBO) associated with the procedure. RESULTS: During the study period, EUS-HGAS without dilation device usage was attempted for 57 patients with MDBO due to pancreatic cancer. The technical and clinical success rates were 91.2% (52/57) each. The median procedural time was 25 min. The rates of early and late AE besides RBO were 3.5% (2/57) and 1.9% (1/52), respectively. The incidence rate of RBO was 30.8% (16/52), and the median time to RBO was 245 days. The rate of successful endoscopic reintervention for RBO via the fistula was 100% (16/16). CONCLUSIONS: EUS-HGAS without the use of dilation devices showed good technical feasibility with a low AE rate. It may be a useful option for MDBO associated with pancreatic cancer when the transpapillary approach is difficult.

Examining the efficacy and safety of endobiliary radiofrequency ablation for ingrowth occlusion after metal stent placement using a bovine model.

BACKGROUND: Although endobiliary radiofrequency ablation (RFA) may be an option for the treatment of ingrowth occlusion after self-expandable metal stent (SEMS) deployment, its utility remains uncertain. This study aimed to clarify its utility and safety using bovine liver. METHODS: A prototype multifunctional RFA catheter and conventional uncovered SEMS were employed in this experimental study. We devised three model types: the ingrowth-ablation, ingrowth-ablation with stent-wire contact (created such that the electrodes were in contact with the metal stent-wire), and standard-ablation models (control). The study outcome was the ablation depth associated with RFA, which was compared among the three models. RESULTS: Thirty-six ablation procedures were conducted (12 for each of the 3 models). In the unipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was significantly lower than that of the ingrowth-ablation (2.0 mm, p = 0.005) and standard-ablation models (2.3 mm, p = 0.004). There was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.563). In the bipolar mode, the median ablation depth with the stent-wire contact model (1.0 mm) was also significantly lower than that of the ingrowth-ablation (2.1 mm, p = 0.008) and standard-ablation models (2.0 mm, p = 0.011), and there was no significant difference between the ingrowth-ablation and standard-ablation models (p = 0.807). Scorching around the stent-wire was not observed in any specimen. CONCLUSIONS: In this ex vivo study, endobiliary RFA for ingrowth occlusion can be considered a useful modality, but the ablation effect is diminished when the electrode comes into contact with the stent-wire.

Mac-2 binding protein glycosylation isomer, the FIB-4 index, and a combination of the two as predictors of non-alcoholic steatohepatitis.

Approximately 10% non-alcoholic fatty liver disease (NAFLD) cases progress to non-alcoholic steatohepatitis (NASH). Liver biopsy, the gold standard for diagnosing NASH and associated liver fibrosis, is invasive with a risk of life-threatening complications. Therefore, reliable non-invasive biomarkers for predicting NASH are required to prevent unnecessary liver biopsies. We evaluated the performance of two non-invasive fibrosis markers, Mac-2 binding protein glycosylation isomer (M2BPGi) and the FIB-4 index for predicting the fibrosis staging, NAFLD activity scoring (NAS) index, and NASH. We also analyzed the correlation between the two markers. The sensitivities, specificities, positive predictive values (PPV), and negative predictive values of the FIB-4 index, M2BPGi, and a combination of both markers for NASH diagnosis were evaluated. The M2BPGi and FIB-4 index showed a good performance in diagnosing NASH, the fibrosis stage, and the NAS index in NAFLD patients. While both markers were well-correlated with each other in most cases, no correlation was found in some patients. Compared with the FIB-4 index or the M2BPGi alone, a combination of the two showed a higher specificity, PPV, and accuracy for NASH diagnosis. The M2BPGi and the FIB-4 index are easily accessible and reliable liver fibrosis markers. Diseases other than liver disease may cause dissociation between the two markers, causing failure to predict NASH. However, the combination of both markers can compensate for their disadvantages. Because the PPV of the combination was relatively high, patients who test positive for both markers should undergo liver biopsy for NASH diagnosis.

Endobiliary Radiofrequency Ablation Combined with Gemcitabine and Cisplatin in Patients with Unresectable Extrahepatic Cholangiocarcinoma.

BACKGROUND: Endobiliary radiofrequency ablation (RFA) is a promising treatment modality for patients with extrahepatic cholangiocarcinoma (eCCA). However, no study has investigated the combined use of endobiliary RFA and gemcitabine plus cisplatin (GC) chemotherapy. This study aimed to examine the feasibility and efficacy of endobiliary RFA with GC therapy for patients with unresectable eCCA. METHODS: The study outcomes included overall survival (OS), progression-free survival (PFS), time to recurrent biliary obstruction (RBO), and adverse events associated with the treatment. These parameters were retrospectively compared between 25 patients who underwent RFA with self-expandable metal stent (SEMS) placement followed by GC therapy (with-RFA group) and a control cohort of 25 patients who underwent SEMS placement alone and GC therapy (without-RFA group). RESULTS: The median time to RBO was significantly longer in the with-RFA group (10.7 versus 5.2 months, p = 0.048). The median OS was significantly higher in patients with locally advanced tumors in the with-RFA group (23.1 versus 16.6 months, p = 0.032), but did not differ significantly in patients with metastasis (11.4 versus 8.5 months, p = 0.180). Similarly, the median PFS was significantly higher in the with-RFA group in patients with locally advanced disease (10.1 versus 7.3 months, p = 0.015), while there was no significant difference in patients with metastasis (5.4 versus 4.4 months, p = 0.529). The rates of various toxicities did not differ significantly between the groups. CONCLUSIONS: Endobiliary RFA prolonged the patency period of uncovered SEMS combined with GC therapy in patients with eCCA. Although RFA also yielded survival benefits, its effect was restricted to locally advanced tumors.

Endobiliary Radiofrequency Ablation Using a Short-Type Balloon Enteroscope in Patients with Surgically Altered Anatomy.

BACKGROUND: Endoscopic radiofrequency ablation (RFA) is expected to prolong stent patency for malignant biliary obstruction (MBO). However, its feasibility when used in conjunction with a balloon enteroscope (BE) in patients with surgically altered anatomy (SAA) remains unknown. AIMS: This study aimed to investigate the feasibility of RFA combined with metal stent insertion under BE guidance for MBO in patients with SAA. METHODS: Thirty-seven patients who underwent treatment between October 2016 and January 2021 and met the eligibility criteria were investigated retrospectively. Study outcomes included technical and clinical success, recurrent biliary obstruction (RBO), and other adverse events besides RBO associated with RFA with metal stent placement using BE. RESULTS: Technical and clinical success rates were 100% (37/37) each. The rates of early and late adverse events were 8.1% (3/37) and 8.1% (3/37), respectively. RBO occurred in 32.4% (12/37) of the patients, and the median time to RBO was 296 days. The cause of RBO was ingrowth in eight patients, overgrowth in three patients, and indeterminate in one patient. All reinterventions for RBO were successful using the BE approach; all ingrowths, except one, were recanalized using additional RFA without additional stent placement. The frequency of reintervention-related adverse events was 9.1% (1/11). The median time to RBO after reintervention was 166 days. CONCLUSIONS: This study demonstrated the technical safety and feasibility as well as good long-term outcomes of endobiliary RFA combined with metal stent placement under BE guidance. This approach may be a useful option for treating MBO in patients with SAA.

Safety and Efficacy of Gemcitabine Plus Nab-Paclitaxel for Metastatic Pancreatic Cancer Patients Undergoing Biliary Stent Placement.

BACKGROUND: Gemcitabine plus nab-paclitaxel (GnP) is the first-line chemotherapeutic regimen for metastatic pancreatic cancer (MPC); however, there are concerns regarding its safety in patients undergoing biliary stent placement. This study aimed to examine the tolerability and efficacy of GnP in MPC patients who underwent biliary stent placement. METHODS: A total of 105 MPC patients who had received GnP treatment between 2015 and 2020 were included and investigated. The patients were divided into two groups: those undergoing biliary stent placement for symptomatic biliary obstruction (BO) (With-BO group) and those without biliary stent placement (Without-BO group). The best tumor response, overall survival (OS), and adverse events in each group were compared. RESULTS: The partial response, stable disease, and progressive disease rates were 22%, 61%, and 14.6% in the With-BO group, and 26.6%, 46.9%, and 21.9% in the Without-BO group, respectively, with no significant differences. The median OS was 12.2 months and 14.6 months in the With-BO and Without-BO groups, respectively (P = 0.483). Grade 3 or higher biliary tract-related events were significantly more common in the With-BO group (41.5%) than in the Without-BO group (1.6%) (P < 0.001), but all events were managed successfully by urgent intervention. The rates of any treatment-related toxicities, including febrile neutropenia, were not significantly different, and there were no chemotherapy-related deaths in either group. CONCLUSIONS: GnP can be as tolerable and effective in MPC patients with biliary stents as in those without biliary stents. However, careful management and appropriate reintervention to treat biliary tract-related adverse events are required.