Deep learning and digital pathology powers prediction of HCC development in steatotic liver disease.

BACKGROUND AND AIMS: Identifying patients with steatotic liver disease who are at a high risk of developing HCC remains challenging. We present a deep learning (DL) model to predict HCC development using hematoxylin and eosin-stained whole-slide images of biopsy-proven steatotic liver disease. APPROACH AND RESULTS: We included 639 patients who did not develop HCC for ≥7 years after biopsy (non-HCC class) and 46 patients who developed HCC <7 years after biopsy (HCC class). Paired cases of the HCC and non-HCC classes matched by biopsy date and institution were used for training, and the remaining nonpaired cases were used for validation. The DL model was trained using deep convolutional neural networks with 28,000 image tiles cropped from whole-slide images of the paired cases, with an accuracy of 81.0% and an AUC of 0.80 for predicting HCC development. Validation using the nonpaired cases also demonstrated a good accuracy of 82.3% and an AUC of 0.84. These results were comparable to the predictive ability of logistic regression model using fibrosis stage. Notably, the DL model also detected the cases of HCC development in patients with mild fibrosis. The saliency maps generated by the DL model highlighted various pathological features associated with HCC development, including nuclear atypia, hepatocytes with a high nuclear-cytoplasmic ratio, immune cell infiltration, fibrosis, and a lack of large fat droplets. CONCLUSIONS: The ability of the DL model to capture subtle pathological features beyond fibrosis suggests its potential for identifying early signs of hepatocarcinogenesis in patients with steatotic liver disease.

Comparison of Efficacy between Pemafibrate and Omega-3-Acid Ethyl Ester in the Liver: the PORTRAIT Study.

AIM: No pharmacotherapeutic treatment has been established for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). This trial compared the effects of pemafibrate and omega-3-acid ethyl ester on hepatic function in patients with hypertriglyceridemia complicated by MASLD. METHODS: Patients with hypertriglyceridemia complicated by MASLD were enrolled, randomly assigned to the pemafibrate or omega-3-acid ethyl ester group, and followed for 24 weeks. The primary endpoint was the change in alanine aminotransferase (ALT) from baseline to week 24. The secondary endpoints included other hepatic enzymes, lipid profiles, and hepatic fibrosis biomarkers. RESULTS: A total of 80 patients were enrolled and randomized. The adjusted mean change in ALT from baseline to week 24 was significantly lower in the pemafibrate group (-19.7±5.9 U/L) than in the omega-3-acid ethyl ester group (6.8±5.5 U/L) (intergroup difference, -26.5 U/L; 95% confidence interval, -42.3 to -10.7 U/L; p=0.001). Pemafibrate significantly improved the levels of other hepatic enzymes (aspartate aminotransferase and gamma-glutamyl transpeptidase), lipid profiles (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol), and hepatic fibrosis biomarkers (Mac-2 binding protein glycan isomer and Fibrosis-4 index). No cases of discontinuation due to adverse drug reactions were identified in either group, and there were no safety concerns. CONCLUSIONS: Pemafibrate is recommended over omega-3-acid ethyl ester for lipid management and MASLD treatment in patients with hypertriglyceridemia complicated by MASLD. The study results may contribute to the development of future treatment strategies for patients with MASLD/MASH.

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.

Endoscopic intraductal radiofrequency ablation for extrahepatic cholangiocarcinoma: An update (2023).

Recently, endoscopic intraductal radiofrequency ablation (ID-RFA) has attracted attention as a local treatment method for malignant biliary obstruction (MBO). ID-RFA causes coagulative necrosis of the tumor tissue in the stricture and induces exfoliation. Its effects are expected to extend the patency period of biliary stents and prolong the survival period. Evidence for extrahepatic cholangiocarcinoma (eCCA) is gradually accumulating, and some reports show significant therapeutic effects in eCCA patients without distant metastasis. However, it is still far from an established treatment technique, and many unsolved problems remain. Therefore, when performing ID-RFA in clinical practice, it is necessary to understand and grasp the current evidence well and to operate appropriately for the true benefit of the patients. This paper reviews the current status, issues, and prospects of endoscopic ID-RFA for MBO, especially for eCCA.

Comparison of the mechanical properties of retrieval basket catheters for bile duct stones: An experimental study.

BACKGROUND: Although numerous retrieval baskets are currently available for the extraction of bile duct stones, their mechanical properties have not been evaluated. This study aimed to ascertain the characteristics of retrieval baskets for bile duct stones by examining their mechanical properties. METHODS: This experimental study tested the mechanical properties of seven retrieval baskets for bile duct stones. The radial force (RF) was measured using a dedicated measurement device and the axial force (AF) was measured using the conventional manual method. RESULTS: The mean RF differed significantly among the baskets (p < 0.001) and was the strongest for VorticCatch (1.62 N ± 0.02) and COAXIS (1.62 N ± 0.04), followed by RASEN (1.27 N ± 0.02), Memory Basket (0.95 N ± 0.01), 8-wire Nitinol Basket (0.93 N ± 0.01), StoneHunter (0.78 N ± 0.01) and Flower Basket (0.37 N ± 0.01), respectively. The mean AF differed significantly among the baskets (p < 0.001) and was the highest for VorticCatch (0.668 N ± 0.032), followed by COAXIS (0.629 N ± 0.041), StoneHunter (0.574 N ± 0.037), 8-wire Nitinol Basket (0.546 N ± 0.010), Memory Basket (0.542 N ± 0.024), RASEN (0.435 N ± 0.008) and Flower Basket (0.297 N ± 0.011), respectively. The baskets were categorized into four groups with comparable mechanical properties based on the RF and AF: group 1, low RF and low AF; group 2, moderate RF and moderate AF; group 3, high RF and moderate AF; and group 4, high RF and high AF. CONCLUSIONS: This study revealed distinct mechanical properties of various retrieval baskets used for extracting bile duct stones, which may enhance the understanding of their action. Our results could also aid the development of retrieval baskets in future.

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

N/A.

A novel non-slip banded balloon catheter for endoscopic sphincteroplasty: an ex vivo and in vivo pilot study.

Endoscopic balloon sphincteroplasty is an established procedure for the extraction of bile duct stones. However, the balloon often slips during the inflation process, and its length is an impediment if the distance between the papilla and scope is limited and/or the stone is located close to the papilla. This animal experimental study aimed to evaluate the feasibility of a novel short non-slip banded balloon measuring 15-20 mm in length for sphincteroplasty. The ex vivo component of this study was conducted using porcine duodenal papilla. Miniature pigs were subjected to endoscopic retrograde cholangiography in the in vivo component. The technical success of sphincteroplasty without any slippage was the primary outcome of the study and was compared between cases managed with the non-slip banded balloon (non-slip balloon group) and conventional balloon (conventional balloon group). The technical success rate of the ex vivo component, i.e., absence of any slippage, was significantly higher in the non-slip balloon group than in the conventional balloon group with the 8-mm (96.0% vs. 16.0%, P < 0.001) and 12-mm diameter balloons (96.0% vs. 0%, P < 0.001). The technical success rate of endoscopic sphincteroplasty without slippage in the in vivo component was significantly higher in the non-slip balloon group than in the conventional balloon group (100% vs. 40%, P = 0.011). No immediate adverse events were observed in either group. The slippage rate was significantly lower with sphincteroplasty using a non-slip balloon, despite the balloon length being considerably shorter than that of conventional balloons, demonstrating its potential utility in difficult cases.

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.

Recent Updates on Local Ablative Therapy Combined with Chemotherapy for Extrahepatic Cholangiocarcinoma: Photodynamic Therapy and Radiofrequency Ablation.

Although chemotherapy constitutes of the first-line standard therapy for unresectable extrahepatic cholangiocarcinoma, the treatment outcomes are unsatisfactory. In recent years, local ablative therapy, which is delivered to the cholangiocarcinoma lesion via the percutaneous or endoscopic approach, has garnered attention for the treatment of unresectable, extrahepatic cholangiocarcinoma. Local ablative therapy, such as photodynamic therapy and radiofrequency ablation, can achieve local tumor control. A synergistic effect may also be expected when local ablative therapy is combined with chemotherapy. However, it is a long way from being entrenched as an established therapeutic technique, and several unresolved problems persist, including the paucity of evidence comparing photodynamic therapy and radiofrequency ablation. Clinical application of photodynamic therapy and radiofrequency ablation requires sound comprehension and assimilation of the available evidence to truly benefit each individual patient. In this study, we reviewed the current status, issues, and future prospects of photodynamic therapy and radiofrequency ablation for extrahepatic cholangiocarcinoma, with a special focus on their combination with chemotherapy.

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.

Long-Term Impact of Endoscopic Gallbladder Stenting for Calculous Cholecystitis in Poor Surgical Candidates: A Multi-center Comparative Study.

BACKGROUND: Although long-term stent placement using endoscopic gallbladder stenting (EGBS) reportedly reduces cholecystitis recurrence in patients unfit to undergo cholecystectomy, its efficacy and safety remain uncertain. AIMS: This study aimed to examine the long-term effect of EGBS in poor surgical candidates of cholecystectomy. METHODS: A total of 528 high-risk surgical patients with acute calculous cholecystitis met this study's eligibility criteria. The technical success and adverse events (AE) were compared between patients who underwent EGBS and those who underwent percutaneous transhepatic gallbladder drainage (PTGBD). Elective stent exchange and removal were not performed after EGBS. The external tube was removed after improvement of cholecystitis following PTGBD. RESULTS: The technical success rate was significantly lower with EGBS compared to PTGBD (75.4% versus 98.7%, P < 0.001), while the early-AE rate did not differ significantly between the two methods (7.7% versus 4.3%, P = 0.146). The 1-, 3-, and 5-year cumulative incidence rates of cholecystitis were 3.8%, 7.2%, and 7.2% with EGBS, and 11.7%, 17.6%, and 30.2% with PTGBD, respectively (P = 0.001). Conversely, those of symptomatic late-AE (except cholecystitis) were 8.2%, 22.7%, and 31.4% with EGBS, and 7.5%, 10.9%, and 13.1% with PTGBD, respectively (P = 0.035). Thus, the 1-, 3-, and 5-year cumulative incidence of overall late-AE was 12.0%, 30.4%, and 40.4% with EGBS, and 19.2%, 28.3%, and 42.5% with PTGBD, respectively (P = 0.649). CONCLUSIONS: Long-term stent placement via EGBS is useful for preventing the recurrence of cholecystitis, but the success rate is low and the frequency of other late-AE increases with the prolongation of the indwelling period.

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.

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.