Publications by authors named "Naoya Kato"

252 Publications

Real-world outcomes of molecular targeted agents for patients with hepatocellular carcinoma over 80 years old.

Hepatol Res 2022 Aug 3. Epub 2022 Aug 3.

Division of Interventional Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-Cho, Sunto-Gun, Shizuoka, 411-8777, Japan.

Aim: There is insufficient evidence regarding the safety and efficacy of molecular targeted agents (MTAs) for elderly patients with hepatocellular carcinoma (HCC), who are likely to be vulnerable to adverse events (AEs) of therapy. The aim of this study was to compare sorafenib and lenvatinib use in elderly patients with HCC from the viewpoint of overall survival (OS) and rate of AE-induced MTA discontinuation.

Methods: This retrospective study included patients with HCC over 80 years old who received first-ine molecular targeted therapy (MTT) at four hospitals between June 2009 and September 2019. They were divided into three groups according to the era and type of first-line MTA: E1-Sora (sorafenib, between 2009 and 2016), E2-Sora (sorafenib, between 2017 and 2019), and E2-Len (lenvatinib, between 2017 and 2019).

Results: The study included 173 patients (E1-Sora: n=79, E2-Sora: n=50, E2-Len: n=44) with a median age of 81.9 years (range 80-93). Median OS was 15.1 months in the entire cohort (E1-Sora, 12.7 months; E2-Sora, 20.5 months; E2-Len, 10.3 months). The rate of treatment discontinuation due to AEs was high in the entire cohort, especially in E1-Sora and E2-Len (49.4% in E1-Sora, 28.0% in E2-Sora, and 54.6% in E2-Len, p=0.0753). More E2-Sora patients received subsequent MTT than E2-Len patients (E2-Sora, 50%; E2-Len, 28.6%; p=0.0111).

Conclusion: Both sorafenib and lenvatinib were effective and feasible for elderly patients with HCC. In terms of discontinuation due to AEs and subsequent MTT, sorafenib might be more desirable for old patients with HCC over 80 years. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13818DOI Listing
August 2022

Genomic profiling amplifies the utility of endoscopic ultrasound-guided fine needle biopsy by identifying clinically applicable druggable mutations in pancreatic cancer.

Ann Diagn Pathol 2022 Jul 22;60:152016. Epub 2022 Jul 22.

Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan; Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan; University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Background: Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations.

Methods: We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES). In total, 20 and 53 formalin-fixed paraffin-embedded tissues obtained via surgery and EUS-FNB were analyzed, respectively. First, we examined the DNA quality and genomic profiles of 20 paired samples from 20 malignant lesions obtained via surgery and EUS-FNB. We then tested 33 samples obtained via EUS-FNB from 24 malignant and 9 benign lesions for the discrimination of malignancy. Finally, we explored drug-matched mutations from EUS-FNB specimens.

Results: Although the DNA quantity obtained via surgery was higher than that obtained via EUS-FNB (P = 0.017), the DNA quality and mean depth were equivalent (P = 0.441 and P = 0.251). Panel sequencing of EUS-FNB specimens identified more oncogenic mutations than WES (90 % vs. 50 %). Furthermore, the number of oncogenic mutations did not differ between EUS-FNB and surgically resected specimens. Genomic profiling of EUS-FNB specimens enabled the discrimination of malignancy with 98 % accuracy. Of 44 malignant lesions, drug-matched alterations were identified in 14 % (6/44) of malignant lesions.

Conclusion: EUS-FNB specimens can be widely utilized for diagnostic purposes, discrimination of malignancy, and detection of drug-matched mutations for the treatment of pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2022.152016DOI Listing
July 2022

The RNA-Binding Protein ELAVL1 Regulates Hepatitis B Virus Replication and Growth of Hepatocellular Carcinoma Cells.

Int J Mol Sci 2022 Jul 17;23(14). Epub 2022 Jul 17.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

Previous RNA immunoprecipitation followed by proteomic approaches successfully demonstrated that Embryonic Lethal, Abnormal Vision, Drosophila-Like 1 (ELAVL1) interacts with hepatitis B virus (HBV)-derived RNAs. Although ELAVL family proteins stabilize AU-rich element (ARE)-containing mRNAs, their role in HBV transcription remains unclear. This study conducted loss-of-function assays of ELAVL1 for inducible HBV-replicating HepAD38 cells and -overexpressed HepG2 cells. In addition, clinicopathological analyses in primary hepatocellular carcinoma (HCC) surgical samples were also conducted. Lentivirus-mediated short hairpin RNA knockdown of resulted in a decrease in both viral RNA transcription and production of viral proteins, including HBs and HBx, probably due to RNA stabilization by ELAVL1. Cell growth of HepAD38 cells was more significantly impaired in -knockdown than those in the control group, with or without HBV replication, indicating that ELAVL1 is involved in proliferation by factors other than HBV-derived RNAs. Immunohistochemical analyses of 77 paired HCC surgical specimens demonstrated that diffuse ELAVL1 expression was detected more frequently in HCC tissues (61.0%) than in non-tumor tissues (27.3%). In addition, the abundant expression of ELAVL1 tended to affect postoperative recurrence in HBV-related HCC patients. In conclusion, ELAVL1 contributes not only to HBV replication but also to HCC cell growth. It may be a potent therapeutic target for HBV-related HCC treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms23147878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316910PMC
July 2022

Successful endoscopic retrieval of a migrated pancreatic stent using a basket catheter for peroral cholangioscopy through a biliary plastic stent pusher tube: a case report.

J Rural Med 2022 Jul 1;17(3):189-192. Epub 2022 Jul 1.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan.

Retrieval is challenging once prophylactic pancreatic stents migrate deep into the pancreatic duct. Herein, we describe a case of successful endoscopic retrieval of a migrated prophylactic pancreatic stent using a basket catheter through a biliary plastic stent pusher tube. A 71 year-old man was referred to our hospital for removal of a straight-shaped migrated 5-Fr 3-cm prophylactic pancreatic stent with a flap on the duodenal side. There were no subjective symptoms at the time of the hospital visit. During endoscopic retrograde cholangiopancreatography, we inserted an 8.5-Fr plastic biliary stent pusher tube in front of the migrated pancreatic stent. The stent was then grasped using a basket catheter for peroral cholangioscopy through the biliary stent pusher tube. The stent was pulled into the pusher tube and was successfully retrieved from the pancreatic duct. No complications were associated with endoscopic retrograde cholangiopancreatography. Although rare, prophylactic pancreatic duct stent migration after pancreatic duct guidewire placement should be noted. In our case, endoscopic retrieval of a migrated prophylactic pancreatic stent using a basket catheter for peroral cholangioscopy through the biliary plastic stent pusher tube was successful.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2185/jrm.2022-003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263960PMC
July 2022

Intraperitoneal bleeding from the right gastroepiploic artery by endoscopic ultrasonography: a case report.

J Rural Med 2022 Jul 1;17(3):184-188. Epub 2022 Jul 1.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan.

To describe the case of a patient with intraperitoneal bleeding from the gastroepiploic artery by endoscopic ultrasound who was successfully treated with transcatheter arterial coil embolization. An 87-year-old man was referred to our hospital for examination of a gallbladder tumor. Endoscopic ultrasonography was performed using an oblique-view echoendoscope. After the endoscopic ultrasound, the patient went into shock. Computed tomography revealed a huge intraperitoneal hematoma and an aneurysm in the right gastroepiploic artery that were not seen on previous computed tomography images. Thus, urgent catheter angiography was performed, which showed a pseudoaneurysm of the right gastroepiploic artery and extravasation of the contrast medium from the pseudoaneurysm. Transcatheter arterial coil embolization was subsequently performed, and the bleeding stopped. Thereafter, his hemodynamics stabilized and his general condition improved. The patient was discharged 22 days post-treatment with an uneventful course. Observation-only endoscopic ultrasound without invasive procedures can cause intraperitoneal bleeding due to a ruptured splanchnic artery. Thus, endoscopic ultrasonography should be performed more carefully in elderly patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2185/jrm.2022-002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263947PMC
July 2022

Detection of actionable mutations in cytological specimens obtained by endoscopic ultrasound-guided fine needle aspiration with rapid onsite evaluation in pancreatic cancer.

Ann Diagn Pathol 2022 Jul 13;60:152008. Epub 2022 Jul 13.

Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan; Department of Gastroenterology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan; University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

Background: It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations.

Methods: A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen.

Results: The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P < 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %).

Conclusion: Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.anndiagpath.2022.152008DOI Listing
July 2022

Adrenomedullin for biologic-resistant Crohn's disease: A randomized, double-blind, placebo-controlled phase 2a clinical trial.

J Gastroenterol Hepatol 2022 Jul 15. Epub 2022 Jul 15.

Department of Projects Research, Frontier Science Research Center, University of Miyazaki, Miyazaki, Japan.

Background And Aim: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD).

Methods: This was a multicenter, double-blind, placebo-controlled phase 2a trial that evaluated 24 patients with biologic-resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24.

Results: No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin-treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin.

Conclusion: In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15945DOI Listing
July 2022

Sofosbuvir-velpatasvir in adults with hepatitis C virus infection and compensated cirrhosis in Japan.

Hepatol Res 2022 Jul 8. Epub 2022 Jul 8.

Department of Hepatology, Toranomon Hospital, Tokyo, Japan.

Background & Purpose: Protease-free regimens for chronic hepatitis C virus (HCV) infection are safe and effective for persons with either compensated or decompensated cirrhosis. We examined the efficacy and safety of sofosbuvir-velpatasvir in participants with HCV and compensated cirrhosis in Japan.

Methods: This was a Phase 3, multi-center, open-label study. At 20 sites, 37 individuals with chronic HCV infection of any genotype and compensated cirrhosis received sofosbuvir-velpatasvir (400 mg/100 mg) daily for 12 weeks. Participants were treatment-naïve or treatment-experienced with interferon-based treatments with or without HCV NS3/4A protease inhibitors. Prior exposure with HCV NS5A or NS5B inhibitors was prohibited. The primary study endpoint was sustained virologic response 12 weeks after treatment (SVR12).

Results: Among participants, 62% had HCV genotype 1 infection, and 38% had HCV genotype 2. More than three quarters (29/37, 78%) were HCV treatment naïve. All participants (37/37, 100%) achieved SVR12. Seventeen participants (46%) and three participants (8%) had pretreatment resistance-associated substitutions to HCV NS5A and NS5B nucleoside inhibitors respectively, yet no on-treatment breakthrough or relapse occurred. Sofosbuvir-velpatasvir for 12 weeks treatment was safe and well tolerated. The most commonly reported adverse events were headache (8%, 3/37) and diarrhea (5%, 2/37). One serious adverse event, patella fracture, occurred and was considered not treatment related. No participants discontinued study treatment due to an adverse event. Three participants (8%) had a Grade 3 laboratory abnormality; all were hyperglycemia.

Conclusion: Sofosbuvir-velpatasvir resulted in high SVR rates and was well tolerated among Japanese patients with HCV and compensated cirrhosis. This single-tablet regimen offers a highly effective, protease-inhibitor free regimen for treating HCV.

Clinicaltrials: gov Identifier: NCT04112303.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13810DOI Listing
July 2022

Successful endoscopic treatment of huge infected biloma and hepatic abscess after endoscopic ultrasound-guided hepaticogastrostomy with brain abscess.

Clin J Gastroenterol 2022 Jun 28. Epub 2022 Jun 28.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.

A 77-year-old woman with obstructive jaundice due to pancreatic head tumor was admitted to our hospital for biliary drainage. Transpapillary biliary drainage was attempted using endoscopic retrograde cholangiopancreatography; however, the catheter could not be inserted into the bile duct. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) was conducted using a 7-Fr plastic stent. Fever and cognitive dysfunction were observed 73 days after EUS-HGS. Abdominal-computed tomography (CT) showed a huge biloma and a liver abscess. On admission, an uncovered metal stent was applied to the biliary obstruction site of the distal bile duct using an antegrade stenting technique, and the plastic hepaticogastrostomy stent was substituted with a new one. On the second day, two double-pigtail plastic stents were inserted into the biloma, and one into the liver abscess. Head CT and magnetic resonance imaging revealed a brain abscess in the right cerebral frontal lobe. Serum white blood cell count and C-reactive protein level, and the state of consciousness, improved with antibiotic administration. Biloma and liver abscess almost disappeared on CT 38 days after admission. The brain abscess also improved, and the patient was discharged from the hospital 48 days after admission. Endoscopic ultrasound-guided biloma drainage is helpful because self-removal of the drainage tube and reduced activities of daily living are unlikely to occur.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12328-022-01659-9DOI Listing
June 2022

Magnified endoscopy with texture and color enhanced imaging with indigo carmine for superficial nonampullary duodenal tumor: a pilot study.

Sci Rep 2022 Jun 20;12(1):10381. Epub 2022 Jun 20.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chiba-City, 260-8670, Japan.

This pilot study aimed to investigate the utility of texture and color enhancement imaging (TXI) with magnified endoscopy (ME) for the preoperative diagnosis of superficial nonampullary duodenal epithelial tumors (SNADETs). We prospectively evaluated 12 SNADETs. The visibility for ME-TXI, ME with indigo carmine (ICME)-white-light imaging (WLI), ICME-TXI compared to ME-NBI (narrow-band imaging) was scored (+ 2 to - 2 ME-NBI was set as score 0) by 3 experts. Scores + 2 and + 1 were defined as improved visibility. The intra-observer and interobserver agreement for improved visibility of surface structure (SS) was evaluated. Sensitivity, specificity, and positive predictive value (PPV) for Vienna Classification (VCL) C4/5 associated with the preoperative diagnosis of ICME-TXI were analyzed. The SS visibility score of ICME-TXI was significantly higher than that of ME-NBI, ME-TXI, and ICME-WLI (P < 0.001 respectively). The kappa coefficients of reliability for intra-observer and interobserver agreement for the SS visibility improvement with ICME-TXI were 0.96, 1.00, 1.00 and 0.70, 0.96, 0.96 respectively. All endoscopists preferred ICME-TXI for visualizing SS mostly for all lesions. The sensitivity, specificity, and PPV (%) of ICME-TXI for VCL C4/5 were 80, 66.7, and 63.2, respectively. ICME-TXI facilitates the visibility of the SS of SNADETs and may contribute to their preoperative diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-14476-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9209444PMC
June 2022

Feasibility of a Single Pigtail Stent Made by Cutting a Nasobiliary Drainage Tube in Endoscopic Transpapillary Gallbladder Stenting for Acute Cholecystitis.

Cureus 2022 May 17;14(5):e25072. Epub 2022 May 17.

Gastroenterology, Chiba University, Chiba, JPN.

Background and objective In this study, we aimed to evaluate the efficacy and safety of a single pigtail stent made by cutting a nasobiliary drainage tube (NBD stent) by comparing the clinical outcomes of using an NBD stent and those of using a ready-made double pigtail stent (RDP stent) in endoscopic gallbladder stenting (EGBS) for acute cholecystitis. Materials and methods This was a single-center retrospective study involving 20 cases that had technical success with EGBS for acute cholecystitis; the patients were divided into two groups: those using NBD stent (NBD group) and those using RDP stent (RDP group). The baseline characteristics and clinical outcomes were compared between the two groups. Results There were 13 patients in the NBD group and seven in the RDP group. The rates of clinical success (NBD group: 92% vs. RDP group: 100%, p=0.45) did not differ significantly between the groups. Regarding adverse events, gallbladder perforation occurred in one case in the NBD group; however, no other adverse events occurred in either group (NBD group: 7.7% vs. RDP group: 0%, p=0.45). The stent patency periods did not differ significantly between the groups [NBD group: 43 (12-64) days vs. RDP group: 97 (58-215) days, p=0.17]. The stent patency period in cases of long-term stent placement after EGBS was 1,381 days and 1,579 days in the NBD group and 305 days in the RDP group, respectively. Conclusion NBD stents are considered as effective as RDP stents in EGBS for acute cholecystitis. They are highly versatile and can be used for both bridging to surgery and long-term stent placement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7759/cureus.25072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202489PMC
May 2022

Synthesis and evaluation of a novel adapter lipid derivative for preparation of cyclic peptide-modified PEGylated liposomes: Application of cyclic RGD peptide.

Eur J Pharm Sci 2022 Sep 15;176:106239. Epub 2022 Jun 15.

Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. Electronic address:

Peptide ligand modified nanoparticles can simply prepared by post-insertion method to mix pre-formed nanoparticles with peptide-lipid conjugates in an aqueous solution at an optimal temperature. Therefore, water dispersibility of peptide-lipid conjugates is a very important factor for implementing the post-insertion method. We proposed that highly water dispersible peptide-lipid conjugates can be easily synthesized by separately designing novel adapter lipids with different water dispersibility and reacting them with ligands in a highly efficient manner. Adapter lipids have three critical roles; as spacers of ligand-conjugated lipids for efficient ligand presentation, as structures that form discrete molecular weight distributions, and as providing water dispersibility. In this study, we developed a novel adapter-lipid derivative that enables a variety of cyclic peptide modifications using the click reaction. The integrin αvβ-targeted cyclic RGDfK (cRGD) peptide was selected as the cyclic peptide ligand. We designed a novel alkyne-tagged lipid with a discrete peptide spacer and bound the cRGD peptide using a click reaction to synthesize a cRGD-conjugated lipid with good water dispersibility for the preparation of cRGD-modified PEGylated liposomes using the post-insertion method. We also revealed that cRGD-modified PEGylated liposomes are efficiently associated with integrin αvβ3-expressing murine colon carcinoma (Colon-26) cells in a modification amount- and peptide sequence-dependent manner, showing high cytotoxicity upon loading with doxorubicin. This novel adapter lipid derivative can be used to synthesize various cyclic peptides by click reactions and will provide useful insights for the future development of cyclic peptide-modified PEGylated liposomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejps.2022.106239DOI Listing
September 2022

Effect of Atezolizumab plus Bevacizumab in Patients with Hepatocellular Carcinoma Harboring Mutation in Early Clinical Experience.

J Cancer 2022 16;13(8):2656-2661. Epub 2022 May 16.

Department of Gastroenterology and Hepatology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Itabashi-ku, Tokyo 173-8610, Japan.

Atezolizumab plus bevacizumab (ATZ/BV) treatment is a combined immunotherapy consisting of immune checkpoint inhibitor (ICI) and anti-vascular endothelial growth factor monoclonal antibody, which has brought a major paradigm shift in the treatment of unresectable hepatocellular carcinoma (HCC). Gain-of-function mutation of contributes to resistance of ICI monotherapy through the framework of non-T-cell-inflamed tumor microenvironment. However, whether mutation renders resistance to ATZ/BV similar to ICI monotherapy remains to be elucidated. In this study, a liquid biopsy sample in plasma of 33 patients with HCC treated with ATZ/BV was subjected to droplet digital PCR for detecting hotspot mutations at the exon 3 of locus. A total of eight patients (24.2%) exhibited at least one mutation. The objective response rate (ORR) in patients with wild-type (WT) and mutant (MT) was 8.0% and 12.5%, respectively, and the disease control rate (DCR) was 68.0% and 87.5%, respectively. No significant difference in both ORR and DCR has been observed between the two groups. The median progression-free survival in patients with WT and MT was 6.6 and 7.6 months, respectively (not statistically significant). Similarly, no significant difference in overall survival has been observed between patients with WT and MT (13.6 vs. 12.3 months). In conclusion, the treatment effect of ATZ/BV in patients with HCC with MT was comparable to those patients with WT . These results implicate that BV added to ATZ might improve immunosuppressive tumor microenvironment caused by mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.71494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174847PMC
May 2022

Liver biopsy technique in the era of genomic cancer therapies: a single-center retrospective analysis.

Int J Clin Oncol 2022 Jun 15. Epub 2022 Jun 15.

Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background: With the evolution of personalized medicine in the field of oncology, which includes optimal treatment selection using next-generation sequencing-based companion diagnostic systems and tumor-agnostic treatments according to common biomarkers, a liver tumor biopsy technique that can obtain a sufficient specimen volume must be established. The current study aimed to evaluate the safety and availability of a liver tumor biopsy technique with multiple puncture sites made using a coaxial introducer needle and embolization with gelatin sponge particles.

Methods: Patients with primary or metastatic liver cancer who underwent liver tumor biopsies with puncture tract embolization using gelatin sponge (Spongel) from October 2019 to September 2020 were included in the study. The complication and diagnostic rates were evaluated, and whether the specimen volume was sufficient for Foundation CDx was investigated.

Results: In total, 96 patients were enrolled in this analysis. The median total number of puncture times per patient was 3 (range 1-8). The pathological diagnostic rate was 79.2%. Using the FoundationOne CDx, specimens with a sufficient volume required for genomic medicine were collected in 84.9% of patients. The incidence rate of bleeding was 4.2% (n = 4), and only one patient presented with major bleeding requiring transfusion.

Conclusions: Liver biopsy with puncture tract embolization using a gelatin sponge may be safe and effective for collecting specimens with a volume sufficient for modern cancer treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10147-022-02195-9DOI Listing
June 2022

A diet-induced murine model for non-alcoholic fatty liver disease with obesity and insulin resistance that rapidly develops steatohepatitis and fibrosis.

Lab Invest 2022 May 28. Epub 2022 May 28.

Department of Gastroenterology, Chiba University, Graduate School of Medicine, Chiba, 260-8677, Japan.

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease worldwide. Patients with NAFLD often suffer steatohepatitis, which can progress to cirrhosis and hepatocellular carcinoma. The presence of visceral obesity or type 2 diabetes mellitus (T2DM) is a major risk factor and potential therapeutic target for NAFLD. The establishment of animal models with these metabolic comorbidities and with the rapid progression of the disease is needed for developing treatments for NAFLD but remains to be archived. In the present study, KK-A mice, widely used as T2DM models, or C57BL6 mice were fed a high-fat, high-fructose, and high-cholesterol diet supplemented with cholic acid (NAFLD diet). The KK-A mice fed a NAFLD diet exhibited remarkable obesity and insulin resistance. A prominent accumulation of triglycerides and cholesterol in the liver was observed at 4 weeks. These mice developed steatohepatitis at 4 weeks and fibrosis at 12 weeks. In contrast, C57BL6 mice fed a NAFLD diet remained lean, although they still developed steatohepatitis and fibrosis. In summary, we established a diet-induced murine NAFLD model with the rapid development of steatohepatitis and fibrosis, bearing obesity and insulin resistance. This model could be useful as preclinical models for drug development of NAFLD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41374-022-00807-6DOI Listing
May 2022

Focused ultrasound/microbubbles-assisted BBB opening enhances LNP-mediated mRNA delivery to brain.

J Control Release 2022 Aug 1;348:34-41. Epub 2022 Jun 1.

Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki, Japan. Electronic address:

Messenger RNA (mRNA) medicine has become a new therapeutic approach owing to the progress in mRNA delivery technology, especially with lipid nanoparticles (LNP). However, mRNA encapsulated-LNP (mRNA-LNP) cannot spontaneously cross the blood-brain barrier (BBB) which prevents the expression of foreign proteins in the brain. Microbubble-assisted focused ultrasound (FUS) BBB opening is an emerging technology that can transiently enhance BBB permeability. In this study, FUS/microbubble-assisted BBB opening was investigated for the intravenous delivery of mRNA-LNP to the brain. The intensity of FUS irradiation was optimized to 1.5 kW/cm, at which BBB opening occurred efficiently without hemorrhage or edema. Exogenous protein (luciferase) expression by mRNA-LNP, specifically at the FUS-irradiated side of the brain, occurred only when FUS and microbubbles were applied. This exogenous protein expression was faster but shorter than that of plasmid DNA delivery. Furthermore, foreign protein expression was observed in the microglia, along with CD31-positive endothelial cells, whereas no expression was observed in astrocytes or neurons. These results support the addition of mRNA-LNP to the lineup of nanoparticles delivered by BBB opening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jconrel.2022.05.042DOI Listing
August 2022

Analysis of non-severe acute onset autoimmune hepatitis according to the presence of radiological heterogeneity.

Hepatol Res 2022 May 31. Epub 2022 May 31.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Aim: Diagnosis of acute onset autoimmune hepatitis (A-AIH) has been difficult in that patients may not have typical clinicopathological features of AIH. In our previous reports of severe and fulminant AIH, two-thirds of them showed radiological heterogeneity: hepatic heterogeneous hypoattenuation on unenhanced computed tomography (CT) reflecting heterogeneous distribution of massive hepatic necrosis (severe centrilobular necrosis), which would be beneficial for the diagnosis. In the present study, we analyzed non-severe A-AIH patients with or without radiological heterogeneity and tried to find novel clinical features for supporting the early diagnosis.

Methods: Clinical, biochemical, immunological, radiological and histological features of 42 patients with non-severe A-AIH at community hospitals between 2010 and 2020 were analyzed.

Results: Of 42, 28 patients on whom CT scans were performed and who could be fully analyzed were enrolled. Five patients showed hepatic heterogeneous hypoattenuation on unenhanced CT. There was no significant difference in clinical, biochemical, immunological and histological features at diagnosis between the two groups according to the presence of radiological heterogeneity, although mean minimum prothrombin time activity during the course was lower in patients with heterogeneity without statistical significance (p = 0.080). All responded to treatment well and achieved initial remission within 3 months.

Conclusions: It is possible that patients with non-severe A-AIH show radiological heterogeneity reflecting centrilobular necrosis which is one of important diagnostic features of A-AIH. Accordingly, radiological heterogeneity might be beneficial for the diagnosis of A-AIH in combination with conventional clinicopathological features if it is detected in the absence of features suggestive of other liver diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13799DOI Listing
May 2022

Histological re-evaluation of autoimmune hepatitis with acute presentation.

Liver Int 2022 08 27;42(8):1916-1917. Epub 2022 May 27.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15317DOI Listing
August 2022

Diagnostic criteria for acute-on-chronic liver failure and related disease conditions in Japan.

Hepatol Res 2022 May;52(5):417-421

Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.

The Intractable Hepato-Biliary Disease Study Group of Japan, sponsored by the Ministry of Health, Labor and Wealth, proposed in 2018 that patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having acute-on-chronic liver failure (ACLF) when a deterioration of liver function ("serum bilirubin level of 5.0 mg/dl or more" and "prothrombin time value of 40% or less of the standardized values and/or international normalization rates of 1.5 or more") caused by severe liver damage develops within 28 days after an acute insult, including alcohol abuse, bacterial infection, gastrointestinal bleeding, and the exacerbation of underlying liver diseases. Disease severity can be classified into 4 grades depending on the extent of the deterioration in organ functions, including liver, kidney, cerebral, blood coagulation, circulatory and respiratory functions. The Study Group has since performed an annual nationwide survey of patients with ACLF diagnosed according to the proposed diagnostic criteria as well as those with disease conditions related to ACLF. A total of 501 patients, including 183 patients diagnosed as having ACLF, seen between 2017 and 2019 were enrolled, and univariate and multivariate analyses revealed that the proposed diagnostic criteria were useful for identifying cirrhotic patients with an unfavorable outcome following an acute insult. Consequently, the Study Group determined that the proposed diagnostic criteria should be used in both clinical practice and clinical research as formal diagnostic criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hepr.13763DOI Listing
May 2022

Baseline soluble MICA levels act as a predictive biomarker for the efficacy of regorafenib treatment in colorectal cancer.

BMC Cancer 2022 Apr 20;22(1):428. Epub 2022 Apr 20.

Division of Gastroenterology, Department of Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.

Background: To evaluate the effect of regorafenib on soluble MHC class I polypeptide-related sequence A (MICA) (sMICA) level in vitro. In addition, we clinically examined whether its plasma levels were associated with regorafenib activity in terms of progression-free survival (PFS) in patients with CRC.

Methods: Human CRC cell line HCT116 and HT29 cells were treated with regorafenib and its pharmacologically active metabolites, M2 or M5 at the same concentrations as those in sera of patients. We also examined the sMICA levels and the area under the plasma concentration-time curve of regorafenib, M2 and M5.

Results: Regorafenib, M2, and M5 significantly suppressed shedding of MICA in human CRC cells without toxicity. This resulted in the reduced production of sMICA. In the clinical examination, patients with CRC who showed long median PFS (3.7 months) had significantly lower sMICA levels than those with shorter median PFS (1.2 months) (p = 0.045).

Conclusions: MICA is an attractive agent for manipulating the immunological control of CRC and baseline sMICA levels could be a predictive biomarker for the efficacy of regorafenib treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12885-022-09512-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019943PMC
April 2022

Fusion HBx from HBV integrant affects hepatocarcinogenesis through deregulation of ER stress response.

Virus Res 2022 Jul 14;315:198787. Epub 2022 Apr 14.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. HBV X protein (HBx) is potentially the most oncogenic among HBV-encoding proteins, while HBV integration, which is frequently observed in HCC, contributes to HCC development. However, the molecular mechanism underlying HBV-induced hepatocarcinogenesis remains unclear. In this study, we identified the fusion HBx, the HBx-human fusion protein derived from HBV integrant, in Hep3B cells and investigated its role in hepatocarcinogenesis. The identified full-length fusion mRNA was 3,725 bp in length, and the fusion HBx, which consisted of 1-140 amino acids of HBx followed by 61 amino acids from the human genome, was translated from the fusion mRNA. The fusion HBx knockdown resulted in reduced cell proliferation and invasion, and loss of tumor development in nude mice. Moreover, the fusion HBx, but not wild HBx, provided anchorage-independent growth ability in soft agar although its transactivation ability was abrogated. Microarray analysis revealed that fusion HBx deregulated endoplasmic reticulum (ER) stress response by modifying ATF3, ATF4, and ATF6 transcription. Interestingly, the effects of fusion HBx on ER stress signaling pathway were similar to those of C-terminal truncated HBx, but significantly different from those of wild HBx. Our findings suggest that the fusion HBx plays a significant role in hepatocarcinogenesis by modifying ER stress response and could be an attractive target for the treatment of HBV-induced HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virusres.2022.198787DOI Listing
July 2022

Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial.

BMJ Open 2022 04 8;12(4):e059779. Epub 2022 Apr 8.

National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan.

Introduction: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has the worst prognosis among all phenotypes. This trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle therapy is a safe and synergistically effective treatment in patients with advanced HCC and MVI.

Methods And Analysis: This phase Ib, multicentre (two sites in Japan), open-label, single-arm, investigator-initiated clinical trial will assess durvalumab monotherapy in combination with particle therapy (cohort A) and that of durvalumab plus tremelimumab in combination with particle therapy (cohort B) for patients with advanced HCC with MVI. Cohort A will receive 1500 mg durvalumab every 4 weeks. Cohort B will receive 1500 mg durvalumab every 4 weeks in principle and 300 mg tremelimumab only on day 1 of the first cycle. Carbon-ion radiotherapy will be administered after day 8 of the first cycle. The primary endpoints are rates of any and severe adverse events, including dose-limiting toxicities (DLTs); secondary endpoints are overall survival, 6-month survival, objective response, 6-month progression-free survival and time to progression. Patients are initially enrolled into cohort A. If cohort A treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), the trial proceeds to enrol more patients into cohort B. Similarly, if cohort B treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), a total of 15 patients will be enrolled into cohort B.

Ethics And Dissemination: This study was approved by the ethics committees of the two participating institutions (Chiba University Hospital and National Institutes for Quantum (approval number: 2020040) and Radiological Science and Technology, QST Hospital (approval number: C20-001)). Participants will be required to provide written informed consent. Trial results will be reported in a peer-reviewed journal publication.

Trial Registration Number: jRCT2031210046.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-059779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995959PMC
April 2022

Recent advances in lipid nanoparticles for delivery of nucleic acid, mRNA, and gene editing-based therapeutics.

Drug Metab Pharmacokinet 2022 Jun 5;44:100450. Epub 2022 Feb 5.

Department of Pharmaceutical Informatics, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki, 852-8588, Japan. Electronic address:

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.dmpk.2022.100450DOI Listing
June 2022

Anti-TNFα antibody versus non-anti-TNFα molecular agents for ulcerative colitis patients who failed initial anti-TNFα therapy.

J Gastroenterol Hepatol 2022 Jun 17;37(6):1083-1089. Epub 2022 Mar 17.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background And Aim: Anti-tumor necrosis factor (TNF)α antibody (ATA) and biologics/molecular targeted agents with other mechanisms (non-ATA) are currently available for refractory ulcerative colitis (UC). However, the knowledge about optimal drug selection after the initial treatment with ATA failure is lacking. This study assessed whether the response to the initial ATA could be a basis for selecting subsequent agents in UC patients.

Methods: Ulcerative colitis patients treated with ATA or non-ATA as the subsequent biologic after the failure of initial ATA were retrospectively analyzed. The efficacy at 14 weeks was examined according to the response to initial ATA.

Results: Of 163 patients treated with the first ATA, the efficacy of subsequent ATA and non-ATA was evaluated in 63 and 36, respectively. Remission and response to subsequent-line therapy, regardless of ATA or non-ATA, were lower in patients with primary nonresponse (PNR) to initial ATA than in patients with efficacy to initial ATA (33.3% vs 69.2%, P < 0.01). In patients with PNR to initial ATA, the remission rate with subsequent ATA was significantly lower than with subsequent non-ATA (4.3% vs 26.3%, P = 0.04). In patients who showed efficacy to initial ATA, the remission rate with subsequent ATA was also lower than that with subsequent non-ATA (30.6% vs 56.3%, P = 0.08). PNR with initial ATA was the predictor of PNR to subsequent ATA (odds ratio: 5.62, 95% confidence interval: 1.50-21.7).

Conclusion: Non-ATA may be suitable in UC patients as the subsequent biologics regardless of the outcome of the first ATA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15826DOI Listing
June 2022

Liver cirrhosis is a risk factor for poor prognosis of acute cholangitis caused by choledocholithiasis.

Ann Hepatol 2022 May-Jun;27(3):100696. Epub 2022 Mar 5.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8677, Japan. Electronic address:

Introduction And Objectives: Acute cholangitis, which is characterized by biliary infection and acute liver injury, may impact cirrhosis prognosis. However, the prognosis itself remains unclear.

Materials And Methods: This multicenter retrospective cohort study compared the mortality and liver function change between patients with and without cirrhosis who underwent endoscopic treatment for acute cholangitis caused by choledocholithiasis between January 2004 and December 2019.

Results: We analyzed 699 patients, 44 of whom had cirrhosis. The cirrhotic group had a significantly higher 30-day mortality rate than the noncirrhotic group (14% vs. 1%; P < 0.001). The cirrhotic group also had significantly lower total bilirubin and albumin recovery. However, all patients with cirrhosis who survived achieved total-bilirubin recovery, and 91% achieved albumin recovery within 90 days. In multivariable Cox regression analysis, the independent risk factors for total-bilirubin recovery included cirrhosis (hazard ratio, 0.37; 95%CI, 0.24‒0.58; P < 0.001) and high total-bilirubin level (0.46; 95%CI, 0.34‒0.60; P < 0.001), whereas those for albumin recovery were cirrhosis (0.51; 95%CI, 0.33‒0.79; P = 0.002), high age (0.62; 95%CI, 0.47‒0.82; P < 0.001), organ dysfunction (0.62; 95%CI, 0.39‒0.96; P = 0.03), low albumin level (0.57; 95%CI, 0.36‒0.91; P = 0.02), and high C-reactive protein level (0.73; 95%CI, 0.56‒0.95; P = 0.02).

Conclusions: Patients with cirrhosis complicated with acute cholangitis had poor prognosis. Recovery of liver function after endoscopic treatment was slow; nevertheless, most patients who survived could recover within 90 days.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aohep.2022.100696DOI Listing
May 2022

Corticosteroid use in indeterminate acute liver failure.

Liver Int 2022 05 3;42(5):1209. Epub 2022 Mar 3.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15220DOI Listing
May 2022

Endoscopic band ligation for the removal of colonic polyp invading the diverticulum.

Endoscopy 2022 Feb 28. Epub 2022 Feb 28.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1055/a-1769-4897DOI Listing
February 2022

Evolution of Survival Impact of Molecular Target Agents in Patients with Advanced Hepatocellular Carcinoma.

Liver Cancer 2022 Jan 6;11(1):48-60. Epub 2021 Dec 6.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background And Aims: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet.

Approach And Results: We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009-2012, = 267; period 2: 2013-2016, = 352; period 3: 2017-2019, = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, < 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively ( = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; < 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC.

Conclusions: The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000519868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820147PMC
January 2022

Impact of acute decompensation on the prognosis of patients with hepatocellular carcinoma.

PLoS One 2022 27;17(1):e0261619. Epub 2022 Jan 27.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.

Background/aims: Organ failure in patients with acute decompensation (AD) is a defining characteristic of acute-on-chronic liver failure (ACLF). However, the clinical features of AD during the long-term clinical course of hepatocellular carcinoma (HCC) are still poorly understood. This study aimed to clarify features and impact of AD/ACLF on the prognosis of patients after treatment for HCC.

Methods: This retrospective study enrolled 556 consecutive patients who were initially diagnosed with HCC, and analyses were conducted taking into account HCC treatment type, HCC stage, and presence or absence of cirrhosis.

Results: During follow-up, 299 patients with AD were hospitalized. AD occurrence is closely related to prognosis, regardless of the presence or absence of cirrhosis and HCC stage, and early-onset AD (within 90 days after HCC treatment) has negative impact on prognosis. In the intermediate-advanced-stage group, surgical resection had a positive impact on AD incidence post-treatment. After systemic therapy for HCC, renal impairment was the predictive factors for AD development. The 28/90-day mortality rate was higher among 41 cases (13.7%) with AD who exhibited ACLF as compared with cases without ACLF. AD without cirrhosis had similar ACLF incidence and short-term mortality, compared to AD with cirrhosis. The prognostic model using a decision-tree-based approach, which includes ACLF, bilirubin level, HCC progression, and MELD score is useful for predicting 90- or 28-day mortality after AD diagnosis.

Conclusions: Careful management of patients with HCC who are hospitalized with AD is necessary, considering ACLF, HCC progression, and liver function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261619PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794202PMC
February 2022

Appropriate selection of endoscopic resection for superficial nonampullary duodenal adenomas in association with recurrence.

Gastrointest Endosc 2022 05 20;95(5):939-947. Epub 2022 Jan 20.

Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba-city, Japan.

Background And Aims: The appropriate selection of endoscopic resection for relatively small superficial nonampullary duodenal adenomas (SNADAs) considering recurrence is not completely clarified. Therefore, this study investigated endoscopic resection utility (EMR, underwater EMR [UEMR], and cap-assisted EMR [EMRC]) for SNADAs from the viewpoint of recurrence and short-term outcomes.

Methods: We retrospectively analyzed patients with sporadic SNADAs who underwent EMR, UEMR, and EMRC at Chiba University Hospital between May 2004 and March 2020 and were observed for ≥12 months after endoscopic resection (EMR, 34 patients, 36 lesions; UEMR, 54 patients, 55 lesions; and EMRC, 45 patients, 48 lesions). Outcomes were evaluated using weighted logistic regression analysis. The logistic regression analysis was weighted using propensity scores.

Results: EMRC showed significantly higher en-bloc and R0 resection rates than EMR. All techniques were equally safe. Only 1 case each of intraoperative perforation and postoperative perforation (in 2 different patients) occurred, which were associated with EMRC. UEMR resulted in higher R0 resection and lower postbleeding rates than EMR. Moreover, patients who underwent UEMR showed no perforation. Median observation period per lesion after endoscopic resection was 84 months (range, 16-199) for patients who underwent EMR, 25 months (range, 12-60) for patients who underwent UEMR, and 63 months (range, 12-180) for patients who underwent EMRC. No significant difference was observed between EMR versus UEMR and between EMR versus EMRC in terms of recurrence (odds ratio, .20 [95% confidence interval, .01-2.86; P = .24] and .78 [95% confidence interval, .09-6.84; P = .82], respectively).

Conclusions: Recurrence risk was not different for EMR, UEMR, and EMRC. Therefore, UEMR, a simple and safe procedure, could be the first choice for relatively small SNADAs. With larger prospective studies, UEMR data may turn out to be more robust, corroborating it as the endoscopic modality of choice for certain SNADAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gie.2022.01.006DOI Listing
May 2022
-->