Natural history of asymptomatic gallbladder stones in clinic without beds:A long-term prognosis over 10 years

BACKGROUND Several studies have explored the long-term prognosis of patients with asymp-tomatic gallbladder stones.These reports were primarily conducted in facilities equipped with beds for addressing symptomatic cases.AIM To report the long-term prognosis of patients with asymptomatic gallbladder stones in clinics without bed facilities.METHODS We investigated the prognoses of 237 patients diagnosed with asymptomatic gallbladder stones in clinics without beds between March 2010 and October 2022.When symptoms developed,patients were transferred to hospitals where appropriate treatment was possible.We investigated the asymptomatic and survival periods during the follow-up.RESULTS Among the 237 patients,214(90.3%)remained asymptomatic,with a mean asymptomatic period of 3898.9279±46.871 d(50-4111 d,10.7 years on average).Biliary complications developed in 23 patients(9.7%),with a mean survival period of 4010.0285±31.2788 d(53-4112 d,10.9 years on average).No patient died of biliary complications.CONCLUSION The long-term prognosis of asymptomatic gallbladder stones in clinics without beds was favorable.When the condition became symptomatic,the patients were transferred to hospitals with beds that could address it;thus,no deaths related to biliary complications were reported.This finding suggests that follow-up care in clinics without beds is possible.

Re-analysis of hepatitis B virus integration sites reveals potential new loci associated with oncogenesis in hepatocellular carcinoma

BACKGROUND Hepatitis B virus(HBV)is a major cause of hepatocellular carcinoma(HCC).HBV DNA can get integrated into the hepatocyte genome to promote carcinogenesis.However,the precise mechanism by which the integrated HBV genome promotes HCC has not been elucidated.AIM To analyze the features of HBV integration in HCC using a new reference database and integration detection method.METHODS Published data,consisting of 426 Liver tumor samples and 426 paired adjacent non-tumor samples,were re-analyzed to identify the integration sites.Genome Reference Consortium Human Build 38(GRCh38)and Telomere-to-Telomere Consortium CHM13(T2T-CHM13(v2.0))were used as the human reference genomes.In contrast,human genome 19(hg19)was used in the original study.In addition,GRIDSS VIRUSBreakend was used to detect HBV integration sites,whereas high-throughput viral integration detection(HIVID)was applied in the original study(HIVID-hg19).RESULTS A total of 5361 integration sites were detected using T2T-CHM13.In the tumor samples,integration hotspots in the cancer driver genes,such as TERT and KMT2B,were consistent with those in the original study.GRIDSS VIRUSBreakend detected integrations in more samples than by HIVID-hg19.Enrichment of integration was observed at chromosome 11q13.3,including the CCND1 pro-moter,in tumor samples.Recurrent integration sites were observed in mitochondrial genes.CONCLUSION GRIDSS VIRUSBreakend using T2T-CHM13 is accurate and sensitive in detecting HBV integration.Re-analysis provides new insights into the regions of HBV integration and their potential roles in HCC development.

Short-and long-term results of endoscopic ultrasoundguided transmural drainage for pancreatic pseudocysts and walled-off necrosis

AIM To evaluate the short-and long-term results of endoscopic ultrasound-guided transmural drainage(EUS-GTD) for pancreatic fluid collection(PFC) and identify the predictive factors of treatment outcome for walled-off necrosis(WON) managed by EUS-GTD alone.METHODS We investigated 103 consecutive patients with PFC who underwent EUS-GTD between September 1999 and August 2015. Patients were divided into four groups as follows: WON(n = 40), pancreatic pseudocyst(PPC; n = 11), chronic pseudocyst(n = 33), and others(n = 19). We evaluated the short-and long-term outcomes of the treatment. In cases of WON, multiple logistic regression analyses were performed to identify the predictor variables associated with the treatment success. In addition, PFC recurrence was examined in patients followed up for more than 6 mo and internal stent removal after successful EUS-GTD was confirmed.RESULTS In this study, the total technical success rate was 96.1%. The treatment success rate of WON, PPC, chronic pseudocyst, and others was 57.5%, 90.9%, 91.0%, and 89.5%, respectively. Contrast-enhanced computed tomography using the multivariate logistic regression analysis revealed that the treatment success rate of WON was significantly lower in patients with more than 50% pancreatic parenchymal necrosis(OR = 17.0; 95%CI: 1.9-150.7; P = 0.011) and in patients with more than 150 mm of PFC(OR = 27.9; 95%CI: 3.4-227.7; P = 0.002).The recurrence of PFC in the long term was 13.3%(median observation time, 38.8 mo). Mean amylase level in the cavity was significantly higher in the recurrence group than in the no recurrence group(P = 0.02).CONCLUSION The reduction of WON by EUS-GTD alone was associated with the proportion of necrotic tissue and extent of the cavity. The amylase level in the cavity may be a predictive factor for recurrence of PFC.

Current status of diagnosis and therapy for intraductal papillary neoplasm of the bile duct

Bile duct epithelial tumours showing papillary neoplasm in the bile duct lumen are present in the intrahepatic and extrahepatic bile ducts.Clinicopathological images of these tumours are distinctive and diverse,including histological images with a low to high grade dysplasia,infiltrating and noninfiltrating characteristics,excessive mucus production,and similarity to intraductal papillary mucinous neoplasm(IPMN)of the pancreas.The World Health Organization Classification of Tumours of the Digestive System in 2010 named these features,intraductal papillary neoplasm of the bile duct(IPNB),as precancerous lesion of biliary carcinoma.IPNB is currently classified into type 1 that is similar to IPMN,and type 2 that is not similar to IPMN.Many of IPNB spreads superficially,and diagnosis with cholangioscopy is considered mandatory to identify accurate localization and progression.Prognosis of IPNB is said to be better than normal bile duct cancer.

Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

The introduction of a direct-acting antiviral(DAA) for patients with hepatitis C virus(HCV) infection, could lead to higher sustained virologic response(SVR)rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma(HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.

Hepatic gene expression profiles associated with fibrosis progression and hepatocarcinogenesis in hepatitis C patients

AIM: To determine fibrosis progression and hepatocellular carcinoma (HCC), using simultaneous gene expression analysis.METHODS: Total RNA samples were extracted from liver biopsies from 19 patients with hepatitis C virus (HCV)infection and 3 patients without HCV infection. Among the 19 HCV-infected patients, 7 and 12 patients had grade F1-2 and F3-4 fibrosis, respectively. Of the 12 patients with F3-4 fibrosis, 8 had HCC. Gene expression in the liver samples was determined using an oligonucleotide microarray. The following comparisons were performed:normal livers vs HCV-infected livers; F1-2 vs F3-4; and F3-4 with HCC vs F3-4 without HCC. Genes that were differentially expressed between these groups were identified based on signal-to-noise ratios.RESULTS: In the HCV-infected livers, genes involved in immune responses were highly expressed. Expression levels of genes for plasma proteins and drug-metabolizing enzymes were decreased and those of genes involved in the cell cycle and oncogenesis were increased in the F3-4 cases as compared to the F1-2 cases. Among the F3-4 cases, genes involved in carbohydrate metabolism tended to be more highly expressed in patients with HCC than in patients without HCC.CONCLUSION: We identified genes that are associated with fibrosis progression and hepatocarcinogenesis. This information may be used to detect increased carcinogenic potential in the livers of patients with HCV infection.

How we use hepatic arterial infusion chemotherapy in the new era of systemic therapy?

The research article by Li et al.demonstrated the clinical benefits of hepatic arterial infusion chemotherapy(HAIC)(also known as transarterial infusion chemotherapy)with FOLFOX compared with transarterial chemoembolization(TACE)and sorafenib in advanced hepatocellular carcinoma(HCC)patients(1).HAIC was still selected as a common treatment option for advanced HCC mostly in Asian countries even when multi-kinase inhibitors were established as the standard treatment.It is believed that experts in Asia fully understand HAIC’s clinical benefit for advanced HCC due to HAIC was a traditional transarterial treatment method which had evolved in Asia and performed before multi-kinase inhibitor development.The biggest reason HAIC had not become the global standard,even with the evidence of high-level efficacy,was the lack of well-designed clinical studies.

Weight-based dosing of Ienvatinib for advanced hepatocellular carcinoma

Lenvatinib is an oral molecular target agent that blocks vascular endothelial growth factor receptors 1-3,fibroblast growth factor receptors 1-4,platelet-derived growth factor receptorα,RET,and KIT.It is noninferior,but not statistically superior,to sorafenib with regard to overall survival,according to the findings of a phase 3 trial of lenvatinib versus sorafenib as first-line therapy for advanced hepatocellular carcinoma(HCC)(the REFLECT trial)(1).Nowadays,lenvatinib has been approved all over the world and has become the second front-line tyrosine kinase inhibitor in patients with advanced HCC.The recommendations for starting lenvatinib therapy for advanced HCC are different from those for other molecular target agents in patient with advanced HCC in that dose is based on body weight(≥60 kg:12 mg once daily;<60 kg:8 mg once daily).The aim of this article is to discuss the weight-based dosing of lenvatinib for advanced HCC.