Comparison of Local Recurrence Between LEN-TACE and TACE for Hepatocellular Carcinoma According to Lipiodol Accumulation.

Background/Aim: Transarterial chemoembolization (TACE) is the standard treatment for patients with hepatocellular carcinoma in the intermediate stage; however, with advances in systemic therapy, the indications for TACE have gained significance. While lenvatinib (LEN)-TACE offers the potential for good outcomes, local recurrence has not yet been adequately investigated. Therefore, this study investigated local recurrence factors for each type of TACE, focusing on the lipiodol (Lip) value in LEN-TACE and conventional TACE. Patients and Methods: Fifty patients (50 nodes) with hepatocellular carcinoma and a tumor size <7 cm who underwent LEN-TACE or TACE between January 2022 and June 2023 were included in this study to investigate local recurrence and its influencing factors. Results: The local recurrence rate after LEN-TACE was 5.6% at 6 months and 11.5% at 12 months, whereas those after TACE were 6.4% at 6 months and 13.2% at 12 months (p=0.028). There were no significant differences in local recurrence rates according to background liver factors, alpha-fetoprotein (AFP), des-γ-carboxy prothrombin (DCP) values, sex, age, and albumin-bilirubin (ALBI) score. Lipiodol (Lip) values immediately after LEN-TACE were significantly higher than those after TACE alone (p=0.021). Multivariate analysis showed that LEN-TACE had a recurrence hazard ratio of 0.184. Conclusion: LEN-TACE provided good local tumor control. Local recurrence factors included LEN pretreatment, and Lip CT values were higher immediately after LEN-TACE. Thus, LEN-TACE after upfront LEN administration may increase the effectiveness of TACE.

RUNX1 expression is regulated by a super-enhancer and is a therapeutic target in adult T-cell leukemia/lymphoma.

Super-enhancers (SEs) play an important role in regulating tumor-specific gene expression. JQ1, a Bromodomain-containing protein 4 (BRD4) inhibitor, exerts antitumor effects by disrupting SE-mediated regulation of gene expression. We investigated the anti-adult T-cell leukemia/lymphoma (ATL) effects of JQ1. JQ1 induced apoptosis and inhibited ATL cell proliferation. JQ1 suppressed RUNX1expression through the disruption of SE-mediated gene regulation. In the previous reports, it was shown that IC50s of AI-10-104 and Ro5-3335, RUNX1 inhibitors were 1-10 µM for lymphoblastic leukemia cell lines carrying RUNX1 mutations. In the present study, we demonstrated that IC50s of AI-10-104 and Ro5-3335 were also 1-10 µM or lower for ATL cell lines. Simultaneously, AI-10-104 suppressed MYC proto-oncogene (c-MYC) expression. RUNX1 is a potential therapeutic target for ATL that promotes c-MYC expression. We showed that RUNX1 expression is regulated via SEs in ATL and that RUNX1 may be a novel therapeutic target for ATL.

A yeast two-hybrid system to obtain triple-helical ligands from combinatorial random peptide libraries.

Many bioactive proteins interact with collagen, recognizing amino acid sequences displayed on the triple helix. We report here a selection strategy to obtain triple-helical peptides that interact with the proteins from a combinatorial random library constructed in yeast cells. This system enables us to select them using the standard two-hybrid protocol, detecting interactions between triple-helical peptides and target proteins fused to the GAL4-activating and binding domains, respectively. The library was constructed having triple-helical peptides with a "host-guest" design in which host helix-stabilizing regions flanked guest random sequences. Using this system, we selected peptides that bind to pigment epithelium-derived factor (PEDF), a collagen-binding protein that shows anti-angiogenic and neurotrophic activities, from the libraries. Two-step selections from the total random library and subsequently from the second focused library yielded new PEDF-binding sequences that exhibited a comparable affinity to or more potent than that of the native PEDF-binding sequence in collagen. The obtained sequences also contained a variant of the PEDF-binding motif that did not match the known motif identified from the native collagen sequences. This combinatorial library system allows the chemical space of triple-helical peptides to be screened more widely than that found in native collagen, thus increasing the expectation of obtaining more specific and high-affinity peptides.

Determinants of Survival of Ablation Treatment for Portal Vein Tumor Thrombus in Patients With Hepatocellular Carcinoma.

BACKGROUND/AIM: The prognosis of hepatocellular carcinoma (HCC) complicated with portal vein tumor thrombus (PVTT) is extremely poor. This study investigated whether local ablation-a curative treatment similar to resection-could improve the prognosis of patients with Child-Pugh B/C PVTT. PATIENTS AND METHODS: Between January 2020 and December 2023, 25 patients with Child-Pugh B/C PVTT HCC were enrolled, and their overall survival with radiofrequency ablation treatment and the associated drivers were investigated. RESULTS: Overall survival (median 282 days) differed between the group treated with transarterial chemoembolization (TACE, 285 days) and the group without it (159 days, p=0.0151). The median survival in the esophagogastric variceal exacerbation group (120.5 days) was shorter than that in the non-exacerbation group (284.0 days, p=0.00964). In multivariate analysis, concomitant TACE had a hazard ratio (HR) of 0.121 (p=0.0097), and the exacerbation of esophagogastric varices had a HR of 6.761 (p=0.01). CONCLUSION: Local ablation for PVTT may promote patient survival specifically by inhibiting the exacerbation of portal hypertension in patients with hepatocellular carcinoma.

Clinical Efficacy and Body Composition Changes with Sodium Glucose Cotransporter 2 Inhibitor/Glucagon-like Peptide-1 Antagonist Combination Therapy in Patients with Type 2 Diabetes Mellitus-associated Nonalcoholic Fatty Liver Disease.

Objective Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) treatment guidelines recommend sodium glucose cotransporter 2 inhibitor (SGLT2I) and glucagon-like peptide-1 agonist (GLP-1A) therapy in patients with type 2 diabetes mellitus (T2DM). SGLT2I improves the pathological condition of NAFLD/NASH in T2DM patients. However, cases of rebound during long-term SGLT2I treatment have been reported. This study investigated the efficacy of SGLT2I and GLP-1A combination therapy in diabetic patients with NAFLD by examining changes in computed tomography (CT)-based body composition and clinical outcomes. Methods Fifteen patients (5 men/10 women) with T2DM-associated NAFLD who had not responded to SGLT2I treatment and were being treated with GLP-1A combination therapy were included. Changes in the liver function, visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI) were compared using CT to evaluate the body composition. Results SGLT2I significantly improved alanine aminotransferase (28.0 to 13.0 IU/L), alkaline phosphatase (250.0 to 77.0 IU/L), and gamma glutamyl transpeptidase (23.0 to 12.0 IU/L) levels. The body mass index (BMI) decreased from 25.7 to 25.2 kg/m2. A CT-based analysis showed a significant improvement in SATI (80.9 to 66.1, p=0.002), with no significant change in VATI (53.2 to 51.5). GLP-1A addition improved the BMI (25.2 to 23.5 kg/m2) and hemoglobin A1c (6.5% to 6.2%, p=0.001). A further analysis revealed additional improvement in SATI (66.1 to 56.6, p=0.007) and a significant decrease in VATI (51.5 to 48.3, p=0.001). Conclusion SGLT2I and GLP-1A combination therapy improved the liver function, body composition, and glycemic control in diabetic patients with NAFLD/NASH, as well as SATI and VATI. The optimal timing of combination therapy remains to be determined.

Efficacy of Adding Locoregional Therapy in Non-Complete Remission Hepatocellular Carcinoma Treated With Atezolizumab Plus Bevacizumab: A Preliminary Study.

BACKGROUND/AIM: Atezolizumab plus bevacizumab (Atez/Bev) therapy is extremely effective and has a high response rate in hepatocellular carcinoma (HCC) treatment. This study investigated the efficacy of adding locoregional therapy with Atez/Bev for non-complete response (CR) HCC cases. PATIENTS AND METHODS: Twenty-eight HCC patients without CR during Atez/Bev therapy received locoregional therapy, and treatment efficacy was evaluated based on the modified RECIST criteria. RESULTS: The study included 23 male and five female participants with a mean age of 73.5 years. In the Atez/Bev and locoregional combination therapy effective group, both transcatheter arterial chemoembolization (TACE) and radiofrequency ablation (RFA) were combined in all patients. A significant reduction in neutrophil-to-lymphocyte ratio (NLR) was observed after adding locoregional therapy (p=0.039). Moreover, a combination of TACE and RFA was performed in all patients of the CR group. When assessing the add-on effect of the combination of TACE and RFA in the progressive disease (PD) group, seven patients were found to achieve non-PD. For patients who did not achieve PD, a significant NLR reduction was noted after the addition of locoregional therapy. CONCLUSION: Adding locoregional therapy such as TACE/RFA was found to exert an effect even in non-CR patients who had received Atez/Bev therapy. A reduction in NLR after locoregional therapy was noted. Even when a response is not obtained during Atez/Bev therapy, it is important to avail the option to add locoregional therapy, as it may contribute to improved prognosis via immune modulation with tolerable adverse reactions.

Refractory gastrocutaneous fistula treated by two-stage surgery: a case report.

BACKGROUND: Gastrocutaneous fistulas are a rare complication of enterocutaneous fistulas and can be caused by intestinal injury, infection, and anastomotic leakage. They are typically treated conservatively or endoscopically; however, for large or difficult-to-treat gastrocutaneous fistulas, surgical intervention is required. Herein, we present a case of a huge gastrocutaneous fistula that was successfully treated with a two-stage surgery performed using open abdomen management. CASE PRESENTATION: A 61-year-old man with a perforated gastric ulcer underwent omental filling as an emergency surgery. Post-operative leakage led the development of a 10-cm gastrocutaneous fistula. He was transferred to our hospital for the treatment of gastrocutaneous fistula. Furthermore, nutritional therapy was administered for dehydration, electrolyte abnormalities, metabolic acidosis, and acute kidney injury due to the high-output nature of the fistula. Moreover, owing to the intraperitoneal severe adhesion and poor nutritional status, two-stage surgery was planned. In the first stage, extensive dissection of the adhesions, distal gastrectomy reconstruction with Roux-en-Y anastomosis, and jejunostomy were performed. Furthermore, open abdomen management was conducted to check for the presence of unexpected complications due to extensive dissection of the adhesion and anastomotic leakage. Subsequently, in the second stage of the surgery, abdominal closure was performed on the 9th day after gastrectomy. CONCLUSION: Open abdomen management may be effective for huge gastrocutaneous fistulas with extensive adhesions that require surgical intervention.

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.

Risk factors for difficult endoscopic hemostasis for colonic diverticular bleeding and efficacy and safety of transcatheter arterial embolization.

This study aimed to investigate the risk factors for difficult endoscopic hemostasis in patients with colonic diverticular bleeding and to evaluate the efficacy and safety of transcatheter arterial embolization (TAE) for colonic diverticular bleeding. This study included 208 patients with colorectal diverticular hemorrhage. The non-interventional radiotherapy group consisted of patients who underwent successful spontaneous hemostasis (n = 131) or endoscopic hemostasis (n = 56), whereas the interventional radiotherapy group consisted of patients who underwent TAE (n = 21). Patient clinical characteristics were compared to identify independent risk factors for the interventional radiotherapy group. Furthermore, the hemostasis success rate, rebleeding rate, complications, and recurrence-free survival were compared between patients who underwent endoscopic hemostasis and those who underwent TAE. Bleeding from the right colon (odds ratio [OR]: 7.86; 95% confidence interval [CI]: 1.6-38.8; P = .0113) and systolic blood pressure <80 mm Hg (OR: 0.108; 95% CI: 0.0189-0.62; P = .0126) were identified as independent risk factors for the interventional radiology group. The hemostasis success rate (P = 1.00), early rebleeding rate (within 30 days) (P = .736), late rebleeding rate (P = 1.00), and recurrence-free survival rate (P = .717) were not significantly different between the patients who underwent TAE and those who underwent endoscopic hemostasis. Patients in the TAE group experienced more complications than those in the endoscopic hemostasis group (P < .001). Complications included mild intestinal ischemia (19.0%) and perforation requiring surgery (4.8%). Patients who required interventional radiotherapy were more likely to bleed from the right colon and presented with a systolic blood pressure of <80 mm Hg. TAE is an effective treatment for patients with colonic diverticular hemorrhage that is refractory to endoscopic hemostasis. However, complications must be monitored carefully.

Prognostic Value of TACE With Irinotecan-loaded Drug-eluting Beads (DEBIRI) in Patients With Liver Metastases from Unresectable Colorectal Cancer.

BACKGROUND/AIM: The standard of care for patients with colorectal cancer and liver metastases, who fail to respond to systemic chemotherapy has not yet been established. Therefore, we investigated the prognostic value of transarterial chemoembolization (TACE) using irinotecan-loaded drug-eluting beads (DEBIRI) in treating liver metastases due to colorectal cancer. PATIENTS AND METHODS: Forty-six patients with colorectal cancer and unresectable liver metastases, who received systemic chemotherapy beyond the third line at our hospital between July 2014 and April 2020 were analyzed. They were divided into two groups: 1) Seventeen patients who received TACE with DEBIRI, and 2) twenty-nine patients who did not receive TACE. RESULTS: The median age was 68 years (range=37-85 years), and the male-to-female ratio was 29:17. The primary sites were the cecum in six cases, ascending colon in seven cases, transverse colon in two cases, descending colon in three cases, sigmoid colon in 14 cases, and rectum in 14 cases. All patients had received at least two prior systemic chemotherapy regimens including oxaliplatin-based and irinotecan-based regimens, and trifluridine tipiracil hydrochloride (38 patients) or regorafenib (12 patients) as the third line or beyond (overlap). Median survival was 272 days overall, 416 days in the TACE group, and 229 days in the non-TACE group, with significantly better survival in the TACE group (p=0.0126). CONCLUSION: TACE with DEBIRI may improve the prognosis of patients with liver metastases from unresectable colorectal cancer. We suggest that TACE with DEBIRI should be highly considered, especially in patients in whom liver metastasis may be a prognostic factor.

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 case report of contrast-enhanced harmonic ultrasonography for the diagnosis of an esophageal duplication cyst.

A 54-year-old man was referred to our hospital because of a suspected esophageal submucosal tumor on upper gastrointestinal radiography. Contrast-enhanced computed tomography showed a 52 mm homogeneous mass attached to the lower thoracic esophagus. Esophagogastroduodenoscopy revealed a 50 mm submucosal tumor in the lower esophagus, and endoscopic ultrasonography (EUS) showed a continuous hypoechoic lesion in the esophageal muscularis propria. Contrast-enhanced harmonic EUS revealed a non-echogenic area. T1 and T2 magnetic resonance imaging revealed a high-signal lesion. Based on imaging studies, an esophageal duplication cyst was diagnosed. Although asymptomatic, the patient underwent video-assisted thoracic surgery because of the possibility of rupture and the appearance of symptoms due to a future infection or enlargement, although this was not noted before. In our case, the esophageal duplication cyst appeared as a hypoechoic mass, requiring differentiation from submucosal tumor other than the cyst. Histologically, the cyst was covered by two layers of muscle covered by the chorioepithelial columnar epithelium. EUS fine-needle aspiration is effective in diagnosing submucosal tumor but also carries the risk of infection. Contrast-enhanced ultrasonography was used in this case to observe the interior and reach a preoperative diagnosis. Contrast-enhanced harmonic EUS appears to be effective in examining the interior of submucosal tumor lesions noninvasively.

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.

Two rare pancreatic parenchymal hemorrhagic lesions associated with acute pancreatitis in acute liver failure: a case report and literature review.

Acute pancreatitis is an uncommon occurrence in acute liver failure. Furthermore, such cases are rarely complicated by parenchymal hemorrhages. Herein, we report the case of a 69-year-old male patient with multiple pancreatic parenchymal hemorrhages concomitant with acute liver failure. The patient underwent conservative treatment for acute liver failure caused by hepatitis B virus infection. Plain computed tomography on the 30th day revealed two high-density mass lesions in the pancreatic body and tail, which were suspected to be multiple pancreatic parenchymal hemorrhages. Despite restarting gabexate mesylate, the patient died of multiple organ failure on the 49th day. The clinical information of the present case and our literature review of 61 similar cases in 43 case reports identified via a systematic keyword search of the PubMed database, which described acute pancreatitis concomitant with acute hepatitis and acute liver failure, will aid physicians in the diagnosis and treatment of this rare condition.

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.).