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.

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.

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.

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.

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 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.

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.).

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.

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.

Updated evidence on the clinical impact of endoscopic radiofrequency ablation in the treatment of malignant biliary obstruction.

Endoscopic biliary radiofrequency ablation (RFA) was recently developed as a novel adjunctive procedure and a promising therapeutic option in patients with malignant biliary obstruction (MBO). RFA can achieve local tumor control, resulting in improved biliary stent patency and a potential survival benefit. However, the efficacy of biliary RFA remains controversial, and previous studies have shown conflicting results. At present, extrahepatic cholangiocarcinoma is considered the condition most effectively treated by biliary RFA, but there is limited research even on this point. Further, limitations of RFA associated with the devices used during the procedure are an important subject of discussion. In addition to further well-designed clinical trials, development of innovative devices is warranted to investigate and conclusively establish the usefulness of biliary RFA. In this review we summarize the updated evidence regarding the use of endoscopic biliary RFA for MBO and discuss issues that should be addressed in future studies.