MicroRNA-34a-5p: A pivotal therapeutic target in gallbladder cancer.

Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer.

BACKGROUND: Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. METHODS: Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. RESULTS: Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. CONCLUSIONS: DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

MicroRNA-451a inhibits gemcitabine-refractory biliary tract cancer progression by suppressing the MIF-mediated PI3K/AKT pathway.

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.

Effects of Yoga and Mindfulness Programs on Self-Compassion in Medical Professionals during the COVID-19 Pandemic: An Intervention Study.

Stress among healthcare workers (HCWs) increased during the coronavirus disease 2019 pandemic. We aimed to determine whether a yoga and mindfulness program could alleviate burnout and other psychological and physical distress in HCWs, and how this might affect their empathy for patients. A weekly one-hour yoga and mindfulness program was conducted for three months in 2021. Participants were 18 consenting HCWs and, the final analysis included 13 participants. They responded to online questionnaires before and after the program. We measured salivary cortisol levels before and after the program on the first and last days. Self-measured pulse rates (PRs) were taken before and after each session, which decreased significantly in both cases (before, after the first program: 72, 65 bpm, p < 0.05; before, after the last program: 75, 66, p < 0.05), but salivary cortisol levels did not change. No significant changes were observed in Patient Health Questionnaire-9, Maslach Burnout Inventory, Sense of Coherence, Connor-Davidson Resilience Scale, Self-compassion Scale, or Jefferson Scale of Empathy. However, common humanity, a subscale of self-compassion, increased significantly (before the first program: 5.6, after the last program: 6.5, p < 0.05), and over-identification decreased significantly (7.9, 6.7, p < 0.01). Yoga and mindfulness programs may help improve the sense of common humanity and reduce over-identification in HCWs.

Statins Inhibit Inflammatory Cytokine Production by Macrophages and Acinar-to-Ductal Metaplasia of Pancreatic Cells.

BACKGROUND AND AIMS: Animal data show that the presence of an oncogenic Kras mutation in pancreatic acinar cells leads to acinar-to-ductal metaplasia (ADM), pancreatic intraepithelial neoplasia (PanIN), and pancreatic ductal adenocarcinoma (PDAC). Inflammatory macrophages play an important role in the formation of ADMs and transition to PanINs. Epidemiologically, statins are associated with a reduced risk of PDAC. We investigated whether statins inhibit inflammatory cytokine production in macrophages and whether this leads to reduced ADM formation. METHODS: The efficacy of statins on inflammatory cytokine production in 2 macrophage cell lines was measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The effect of macrophage-conditioned medium on ADM in primary pancreatic acinar cells was investigated. Mouse pancreatic tissue samples were analyzed for macrophage numbers, cytokine levels, and neoplastic/dysplastic area. RESULTS: Lipophilic statins prevented inflammatory cytokine production in Raw264.7 and J774A.1 cells stimulated by lipopolysaccharide. The inhibitory effect of statins was mediated by inhibition of mevalonate and geranylgeranyl pyrophosphate synthesis and disruption of the actin cytoskeleton but not by a reduction in intracellular cholesterol. Treatment of macrophages with lipophilic statins also blocked ADM formation of primary pancreatic acinar cells. Furthermore, oral administration of simvastatin was associated with a reduction in the number of intrapancreatic macrophages, decreased inflammatory cytokine levels in the pancreas, and attenuated ADM/PanIN formation in mice. CONCLUSION: Our data support the hypothesis that statins oppose early PDAC development by their effects on macrophages and ADM formation. The inhibitory actions of statins on macrophages may collaborate with direct inhibitory effects on transformed pancreatic epithelial cells, which cumulatively may reduce early PDAC development and progression.

Modified line-assisted complete closure of the defect after gastric endoscopic full-thickness resection: a pilot study in porcine models.

Background and study aims Closure after endoscopic full-thickness resection (EFTR) is challenging. We previously developed a simple endoscopic closure method: line-assisted complete closure (LACC). We performed a pilot study using porcine models to evaluate the feasibility of modified LACC after gastric EFTR. Patients and methods Six live pigs were included. EFTR (greater curvature of the gastric antrum [n = 3] and anterior wall of the gastric body [n = 3]) was performed under general anesthesia and the defect after EFTR was closed by modified LACC. The pigs were observed until postoperative day 4 (Day 4). The closure site was endoscopically evaluated and the presence or absence of peritonitis and fluid leakage was evaluated. The outcomes were the success rate of modified LACC on the day of the procedure, maintenance of defect closure, presence of peritonitis or leakage, and clinical course. Results Once complete closure was successfully achieved in all cases, maintenance of closure on Day 4 was not achieved. However, there was neither peritonitis nor fluid leakage. The defect was completely covered by surrounding tissues on Day 4 and the clinical course was good in all cases. Conclusions The feasibility of modified LACC after gastric EFTR was demonstrated in porcine models. Further improvement is needed to maintain defect closure.

Fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection for patients with immunosuppressants and steroids.

Objectives: Transient fever and electrocoagulation syndrome after colorectal endoscopic submucosal dissection (ESD) remain a challenge. The aim of this study was to assess the risk factors of post-ESD fever and post-ESD coagulation syndrome (PECS), focusing on the involvement of immunosuppressive drugs and steroids (IM). Methods: This retrospective analysis included 510 patients who underwent colorectal ESD at Okayama University Hospital from 2015 to 2020. The incidence rate, clinical outcome, and factors associated with post-ESD fever and PECS were investigated. Results: Post-ESD fever and PECS occurred in 63 patients (12.4%) and 43 patients (8.4%), respectively. In multivariate analysis, the American Society of Anesthesiologists Physical Status ≥3, the use of immunosuppressants or prednisolone ≥5mg (IM group), and injury to muscle layer/perforation were significantly associated with post-ESD fever. In PECS, IM group, tumors located on the right side, treatment time ≥60 min, injury to the muscle layer, and multiple lesions were independent risk factors. Both post-ESD fever and PECS improved conservatively in the IM group, and no serious complication was observed. Conclusions: The use of IM was a risk factor for both post-ESD fever and PECS. However, there were no serious complications in colorectal ESD for patients taking IM.

Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer.

BACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed. AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy. METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared. RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p < .01 and p = .01, respectively). Of 10 clinical variables analyzed, plasma KRAS mutation was the factor predictive of DFS in multivariate analysis (RR = 3.58, 95% CI: 1.36-9.60; p = .01). Although 12 patients (31%) given chemotherapy tested positive for plasma KRAS mutations, there was no demonstrable relation between plasma KRAS mutations and progression-free survival (PFS) or overall survival (OS) (p = .35 and p = .68, respectively). CONCLUSIONS: In patients with PDAC, detection of KRAS mutations in plasma proved independently predictive of early recurrence after surgical resection but did not correlate with PFS following chemotherapy.

Direct Effects of Lipopolysaccharide on Human Pancreatic Cancer Cells.

OBJECTIVES: Obesity, a risk factor for pancreatic adenocarcinoma (PDAC), is often accompanied by a systemic increase in lipopolysaccharide (LPS; metabolic endotoxemia), which is thought to mediate obesity-associated inflammation. However, the direct effects of LPS on PDAC cells are poorly understood. METHODS: The expression of toll-like receptor 4, the receptor for LPS, was confirmed in PDAC cell lines. AsPC-1 and PANC-1 cells were exposed to LPS, and differential gene expression was determined by RNA sequencing. The activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway by LPS in PDAC cells was assessed by Western blotting. RESULTS: The expression of toll-like receptor 4 was confirmed in all PDAC cell lines. The exposure to LPS led to differential expression of 3083 genes (426 ≥5-fold) in AsPC-1 and 2584 genes (339 ≥5-fold) in PANC-1. A top canonical pathway affected by LPS in both cell lines was PI3K/Akt/mTOR. Western blotting confirmed activation of this pathway as measured by phosphorylation of the ribosomal protein S6 and Akt. CONCLUSIONS: The exposure of PDAC cells to LPS led to differential gene expression. A top canonical pathway was PI3K/Akt/mTOR, a known oncogenic driver. Our findings provided evidence that LPS can directly induce differential gene expression in PDAC cells.

Human Telomerase Reverse Transcriptase Gene Promoter Mutation in Serum of Patients with Hepatocellular Carcinoma.

BACKGROUND: Mutations in the human telomerase reverse transcriptase (hTERT) gene promoter have been reported in hepatocellular carcinoma (HCC); however, analyses of these mutations in liquid biopsies have been technically difficult because of the high GC content of the regions of interest within this promoter. We evaluated the feasibility and prognostic value of hTERT promoter mutations identified in circulating cell-free DNA (cfDNA) from the serum of patients with HCC. OBJECTIVE: A cohort of HCC patients (n = 36) who were curatively treated by surgical resection between June 2003 and September 2014 were enrolled in this study. METHODS: The presence of hTERT promoter mutations in cfDNA from the patients' serum was analyzed via modified droplet digital polymerase chain reaction, and associations were sought between specific promoter mutations and patients' disease-free survival (DFS). RESULTS: The G>A hTERT mutation at -124 bp was detected in the serum of 25 patients (69%). Although no marked differences were observed between the characteristics of the serum mutation-positive and serum mutation-negative patient groups, the DFS of patients with the mutation was significantly shorter than that of the serum mutation-negative patients (p = 0.02). Among 18 clinicopathologic and background liver factors examined, the presence of the -124 bp G>A mutation was an independent and significant predictor of patients' DFS (hazard ratio = 3.01, 95% confidence interval 1.11-10.5, p = 0.03) in multivariate analyses. CONCLUSIONS: The -124 bp G>A hTERT promoter mutation was observed in the serum of 69% of HCC patients who underwent surgical resection and was an independent predictor of disease progression in HCC.

Evaluation of Local Recurrence of Pancreatic Cancer by KRAS Mutation Analysis Using Washes from Endoscopic Ultrasound-Guided Fine-Needle Aspiration.

BACKGROUND AND AIMS: The sensitivity of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for diagnosing the recurrence of pancreatic cancer is usually low because of difficulties in obtaining adequate samples for pathological examinations. We evaluated the efficacy of highly sensitive KRAS mutation analysis using EUS-FNA washes to detect cancer recurrence. METHODS: Nineteen consecutive patients with suspected pancreatic cancer recurrence after surgical resection were enrolled. All underwent EUS-FNA, and samples were obtained for pathological examination. After the first session, the inside of the FNA needle was washed with saline for DNA extraction. KRAS mutations were examined using digital droplet PCR (dPCR). RESULTS: The median needle puncture number used to obtain adequate pathological samples was two (range 1-6). In ten patients pathologically diagnosed with malignant pancreatic cancer, nine patients tested positive for a KRAS mutation. All patients who were not diagnosed with a malignant pancreatic cancer tested negative for a KRAS mutation. About half of surgically resected primary cancers (9/19) showed double KRAS mutations (G12V and G12D); however, all but one wash sample showed a single KRAS mutation, G12D. After including one patient who showed a malignant recurrence during follow-up, the sensitivities of a pathological diagnosis and KRAS analysis to detect recurrence were 90.9% and 81.8%, respectively. CONCLUSIONS: KRAS mutation analysis of needle wash samples using dPCR is a new methodology for the diagnosis of the local recurrence of pancreatic cancer. The diagnostic ability of dPCR with a one-time needle wash sample was comparable to a pathological diagnosis with multiple samplings.

Utility of liquid biopsy using urine in patients with pancreatic ductal adenocarcinoma.

In recent years, liquid biopsy for blood and body fluid in cancer patients has attracted attention. However, there have been few reports of liquid biopsy focusing on urine of pancreatic ductal adenocarcinoma (PDAC). In 56 patients with PDAC, DNA was extracted from urine and plasma prior to treatment, and KRAS mutations were analyzed with droplet digital PCR to examine the mutation detection rate. Our study showed that KRAS mutations were found in 27 cases (48%) in urine and 27 cases (48%) in plasma. The detection rate of urine KRAS mutations varied by renal functions. The rates were 70% (14/20) and 36% (13/36) in the creatinine clearance rate (CCr) < 70 mL/min group and in the CCr ≥ 70 mL/min group, respectively (P = .024). Whereas, no influence of the CCr was observed in the detection rates of plasma KRAS mutations. The rates were 50% (10/20) and 47% (17/36) in cases with the CCr < 70 mL/min group and the CCr ≥ 70 mL/min group, respectively. Although the sample size was small, this study clearly indicated a new possibility of less invasive urine liquid biopsy in PDAC patients.

[Metachronous intraductal papillary mucinous carcinoma five years after cholecystectomy for gallbladder cancer in a patient with pancreaticobiliary maljunction].

A 71-year-old female with non-dilated pancreaticobiliary maljunction (PBM) and gallbladder polypoid lesions underwent laparoscopic cholecystectomy. Histological examination of the polypoid lesions revealed gallbladder cancer. Five years after cholecystectomy, gradual dilatation of the main pancreatic duct (MPD) led to the identification of a papillary tumor growing in the MPD of the pancreatic head. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Pathological examination revealed a papillary tumor with focal invasion to the MPD. Immunohistochemically, the tumor cells were positive for MUC1 and MUC5AC and negative for MUC2. Therefore, the definitive diagnosis was pancreatobiliary-type intraductal papillary mucinous carcinoma. This case emphasizes the significance of surveillance for potential cancer of the pancreas as well as the biliary tract in patients with PBM.

Liquid biopsy of bile for the molecular diagnosis of gallbladder cancer.

INTRODUCTION: Tissue sampling of gallbladder cancer (GBCa) is challenging because of the anatomy of the gallbladder. The aim of this study is to investigate the possibility of diagnosing GBCa patients by performing a liquid biopsy of bile in addition to current diagnostic methods. METHODS: Thirty patients with GBCa were enrolled in this study. Cytological examination was performed in all patients. Using next generation sequencing (NGS), DNA isolated from the bile and tumor tissue was analyzed for mutations in 49 oncogenes. We also compared these mutations with cytology results. RESULTS: 57.1% of DNA samples from tumor tissue were positive for a mutation. In these patients, 87.5% of the bile circulating tumor DNA (ctDNA) samples had the same mutation. The concordance rate between bile ctDNA and tissue DNA samples was 85.7%, and the mutation frequencies detected in ctDNA were approximately half of what was detected in tumor tissue DNA. On the other hand, the sensitivity of the cytological and bile ctDNA analyses was 45.8% and 58.3%, respectively. The concordance rate between cytology and bile ctDNA analyses was 87.5%. CONCLUSIONS: Mutated tumor DNA could be detected in bile by NGS. Liquid biopsy of bile might help us to diagnose GBCa because of higher sensitivity and positive predict value compared to cytology with ERCP.

Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation.

Transcatheter arterial chemoembolization (TACE) is often performed before radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the tumor size, facilitating complete ablation. However, the factors correlated with size reduction remain uncertain. The aim of this study was to identify the factors associated with size reduction by TACE and develop a formula to predict the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA at least 20 days later were enrolled. The tumor size was measured at the time of TACE and RFA, and correlations between the reduction rate and 13 clinical factors were examined. A formula to predict the reduction rate was built using the factors obtained by the analysis. Reduction in the tumor size was observed in 69 nodules, and the median reduction rate was 16.2%. A multivariate regression analysis revealed that a large tumor size (p< 0.01) and a long interval between the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor size more strongly related to the degree of reduction. A size reduction of more than 10% can be expected by waiting 20 days after TACE when the size of the tumor at TACE is over 25 mm in diameter. The tumor size.

Comparing reduced-dose sodium phosphate tablets to 2 L of polyethylene glycol: A randomized study.

AIM: To compare the tolerability and quality of bowel cleansing between 2 L polyethylene glycol (PEG) and reduced-dose sodium phosphate (NaP) tablets as a preparation for colonoscopy. METHODS: Two hundred patients were randomly assigned to the PEG or NaP groups at the same ratio. The NaP group patients took 30 tablets with 2 L of clear liquid, while the PEG group patients took 2L of PEG. Tolerability was assessed by a questionnaire about taste, volume, and the overall impression. The bowel cleansing quality was evaluated by colonoscopists. RESULTS: Although NaP showed better tolerability in terms of taste, volume and overall impression (P < 0.01, P < 0.01 and P = 0.02, respectively), the overall cleansing quality was better in the PEG group (P < 0.01). A subgroup analysis, stratified by sex and age, indicated that NaP was associated with better tolerability and equivalent bowel cleansing quality in females of < 50 years of age. CONCLUSION: Despite the better tolerability, the use of 30 NaP tablets with 2 L of clear liquid should be limited due to its lower cleansing quality; however, in certain cases the regimen may deserve consideration, particularly in cases involving young women.

Utility of serum DNA as a marker for KRAS mutations in pancreatic cancer tissue.

BACKGROUND/OBJECTIVES: The detection of cancer-specific DNA in peripheral blood, known as a liquid biopsy, has been reported recently. Most such studies have used plasma as a sample; however, whether or not serum can be used as effectively is unclear. We attempted to clarify suitable samples for detecting KRAS mutations in circulating DNA in the blood of pancreatic cancer patients using droplet digital polymerase chain reaction (PCR). METHODS: DNA was extracted from the tissue, plasma, and serum of 40 pancreatic cancer patients. The presence of KRAS mutations G12D, G12V, and G12R was analyzed by droplet digital PCR. RESULTS: The amount of DNA isolated from the serum was much higher than that from plasma (1.0- to 42.0-fold). At least 1 KRAS mutation was observed in 93% of cancer tissues, whereas we detected the mutations in only 48% of the serum and plasma DNA samples. The G12D mutation was the most prevalent of the three mutations, followed by the G12V mutation. The presence of the G12D KRAS mutation in the plasma, serum, or tissue did not correlate to the overall survival; however, the prognosis of the patients with a KRAS mutation at G12V in the plasma or serum was significantly poorer than that of the patients without the mutation (P < 0.01). CONCLUSIONS: Serum and plasma were found to be good materials for detecting cancer-specific DNA in the peripheral blood and the presence of KRAS mutations in blood-derived DNA may be used as a prognostic biomarker for patients with pancreatic cancer.

Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma.

BACKGROUND AND AIM: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC. METHODS: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching. RESULTS: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (>30 mm, hazard ratio = 1.685, P = 0.043), high des-γ-carboxyprothrombin (>100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group. CONCLUSIONS: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

The effect of long-term supplementation with branched-chain amino acid granules in patients with hepatitis C virus-related hepatocellular carcinoma after radiofrequency thermal ablation.

GOALS: To elucidate whether long-term supplementation with branched-chain amino acid (BCAA) granules improves overall survival (OS) and recurrence-free survival (RFS) after radiofrequency thermal ablation (RFA) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of ≤3.5 g/dL. BACKGROUND: Whether BCAA treatment after curative RFA for patients with HCV-related HCC improves OS and RFS remains unclear. STUDY: We compared the OS rate and the RFS rate between the BCAA group (n=115) and the control group (n=141). We also examined factors contributing to OS and RFS. RESULTS: The 1 and 3 years OS rates after RFA were 94.0% and 70.0%, respectively, in the BCAA group, and 94.0% and 49.8%, respectively, in the control group (P=0.001). The corresponding RFS rates 1 and 3 years after RFA were 61.8% and 28.0%, respectively, in the BCAA group, and 52.0% and 12.0%, respectively, in the control group (P=0.013). In the multivariate analysis, in terms of OS, BCAA treatment, and serum albumin level of ≥3.4 g/dL, and in terms of RFS, age 70 years or older, BCAA treatment, and a serum albumin level of ≥3.4 g/dL were significant independent factors, respectively. CONCLUSIONS: BCAA treatment may improve OS and RFS after RFA in patients with HCV-related HCC≤3 cm in diameter with up to 3 nodules and a serum albumin level before RFA of 3.5 g/dL.