Hepatology ResearchVolume 52, Issue 10 p. 893-893 LETTER TO THE EDITOR Anatomical thermal ablation: A valuable treatment method for hepatocellular carcinoma smaller than 5 cm Hang Sun, Hang Sun Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, ChinaSearch for more papers by this authorWei Xu, Wei Xu Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorHuayu Yang, Corresponding Author Huayu Yang dolphinyahy@hotmail.com Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China Correspondence Huayu Yang, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. Email: dolphinyahy@hotmail.comSearch for more papers by this author Hang Sun, Hang Sun Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, ChinaSearch for more papers by this authorWei Xu, Wei Xu Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, ChinaSearch for more papers by this authorHuayu Yang, Corresponding Author Huayu Yang dolphinyahy@hotmail.com Department of Liver Surgery, Peking Union Medical College (PUMC) Hospital, PUMC and Chinese Academy of Medical Sciences, Beijing, China Correspondence Huayu Yang, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. Email: dolphinyahy@hotmail.comSearch for more papers by this author First published: 01 October 2022 https://doi.org/10.1111/hepr.13805 Hang Sun and Wei Xu contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume52, Issue10October 2022Pages 893-893 RelatedInformation

Triptolide (TP) exerts a promising effect in the treatment of ulcerative colitis (UC). However, its toxicity seriously hinders its application in the clinic. Previous studies indicated that dendritic cells (DCs) are the main target through which TP exerts its immunoregulatory effect. Thus, we designed an approach to target DCs in vitro to avoid the direct exposure of organs to TP. Our results revealed that DCs pretreated with TP (DCTP) exerted satisfactory therapeutic effects in mice with colitis, resulting in improved colonic inflammation and alleviated local lesion damage. In addition, no obvious toxicity was observed. DCTP also reshaped the immune milieu by decreasing CD4+ T cell numbers and increasing regulatory T cell numbers in the spleen, mesenteric lymph nodes, peripheral blood and colon; these effects were further confirmed in vitro. Downregulation of CD80/86, ICAM-1, MHCI, TLR2/4, TNF-α, and IL-6 expression and upregulation of programmed cell death ligand 1 (PDL1) and IL-10 expression were observed, indicating that DCs were converted into tolerogenic DCs. In conclusion, DCTP can effectively reduce toxicity and alleviate colonic inflammation and local lesion damage in mice with colitis. The immune mechanism underlying the effects of DCTP included the conversion of DCs into tolerogenic DCs and the alteration of T cell differentiation to produce immunoinhibitory rather than immunostimulatory T cells.

Background: Aging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). The gut microbiota dysbiosis is involved in age-associated diseases. However, whether age-associated gut microbial dysbiosis contributes to AF is still unknown. The aim of this study was to evaluate the effect of gut microbiota on the susceptibility of aging-induced AF and to elucidate the underlying mechanisms. Results: The gut microbiota profiling of fecal samples in aged (22-24 months old) and young (2-3 months old) rats was performed by 16S ribosomal RNA gene analysis. A rat model of fecal microbiota transplantation (FMT) was established for analyzing the possible role of age-associated gut microbial dysbiosis in AF. Here, we found that aging process led to marked shift of the microbiota spectrum. The microbiota in young rats following FMT resembled that of aged microbiota and transmitted the increased AF susceptibility by elevation of circulating lipopolysaccharide (LPS). The mechanism for LPS-driven atrial pro-arrhythmic action was dependent on the activation of atrial nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing (NLRP3)-inflammasome. Inhibition of inflammasome by MCC950 resulted in lower atrial fibrosis and AF susceptibility. In addition, atrial fibrosis, plasma LPS concentration, plasma glucose to oral glucose tolerance test (OGTT), intestinal permeability, and gut pathology were significantly increased in elderly human subjects. Finally, altering the microbiota in aged recipient to resemble that of young restored the intestinal barrier dysfunction and LPS and impaired glucose tolerance, and the worse outcomes of aged dysbiosis on atrial fibrosis and AF susceptibility were abrogated. Conclusions: These data suggest that age-associated microbial dysbiosis induces circulating LPS and impairs glucose tolerance, and thereby promotes AF susceptibility through enhanced activity of atrial NLRP3-inflammasome.

Background Time-restricted feeding (TRF) has been proved to improve general health in adults. However, according to our previous study, this regimen failed to show similar protective effect in pediatric population. Gut microbiota has been proved to play a vital part in the whole process. Although previous studies have defined the commensal flora as a real-time indicator of health conditions in adults, our study aimed to investigate whether the unfavorable TRF feeding schedule during childhood would cause long-term variations in murine model. Methods We randomly assigned 120 4-week-old Kunming mice (half male and half female) to four feeding regimens: TRF.AD, time-restricted feeding during the childhood phase before switched to ad libitum feeding pattern as adults; TRF.TRF, continuously treated with time-restricted feeding; AD.TRF, went through time-restricted feeding only in adulthood; AD.AD, always had ad libitum access to food. After 8 weeks of dietary intervention, faeces were harvested from 12-week-old adult mice (one subject per cage), and gut microbiota was subsequently analysed via DNA extraction and 16s rRNA sequencing. Results Mice on identical diet for four weeks but went through different feeding patterns during childhood showed distinctive traits in gut microbiota. Differences existed in both the α diversity and specific groups of bacteria under different taxonomical levels. Conclusions Feeding pattern in the childhood had long-term impact on mice gut flora that cannot be wiped out in adulthood.

Time-restricted feeding (TRF), that is, no caloric intake for 14-16 hours each day leads to favourable nutritional outcomes. This study is the first to investigate TRF through a surgical perspective verifying its efficacy against liver ischaemia reperfusion (I/R) injury. We randomly assigned 100 10-week-old wild-type male C57BL/6 mice into two feeding regimens: TRF and ad libitum access to food. Main outcomes were evaluated at 6, 12 and 24 hours post-I/R surgery after 12 weeks of intervention. TRF group demonstrated minor liver injury via histological study; lower serum levels of liver enzymes, glucose and lipids; higher concentrations of free fatty acid and β-hydroxybutyrate; decreased oxidative stress and inflammatory biomarkers; as well as less severe cell apoptosis and proliferation. Further exploration indicated better gut microenvironment and intestinal epithelial tight junction function. TRF employed its positive influence on a wide spectrum of biochemical pathways and ultimately revealed protective effect against hepatic I/R injury possibly through adjusting the gut microbiota. The results referred to a strong indication of adopting better feeding pattern for surgical patients.

Background Although patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma derive survival benefit from hepatectomy, prognostic factors and management after curative resection are unclear. This study aims to evaluate predictive factors, therapy and prognosis of intra-hepatic recurrences after curative resection of Barcelona clinic liver cancer stage B or C hepatocellular carcinoma. Methods We retrospectively analyzed 397 patients with Barcelona clinic liver cancer stage B or C hepatocellular carcinoma who underwent curative resections from January 1989 to October 2011. Intra-hepatic recurrences were classified into early (<2 year) and late (≥2 year) recurrences. Results Overall survival rates in our cohort were 1-year: 81.4%; 3-year: 48.5%; and 5-year: 28.2%. Early and late intra-hepatic recurrences developed in 104 patients and 73 patients, respectively. In univariate analysis, overall survival for the non-recurrence group was significantly better than for the recurrence group (P<0.001), and overall survival for the late recurrence group was significantly better than for the early recurrence group (P<0.001). In multivariate analysis, total tumor size, tumor number and vascular invasion were significant risk factors for tumor recurrence (P<0.001). The overall survival of patients with late recurrence who received curative treatment was comparable to those who never had tumor recurrences (P=0.140). Conclusion Time to recurrence and feasibility of curative treatment are the best determinants for prognosis in Barcelona clinic liver cancer stage B or C hepatocellular carcinoma. Curative treatments may prolong overall survival of patients with late recurrences, but should be avoided for those with early recurrences.

AimPrimary clear cell carcinoma of liver (PCCCL) is a specific and rare subtype of primary hepatocellular carcinoma (HCC). We performed a retrospective study with long-term follow-up to investigate predictive factors and prognosis of intrahepatic recurrences of PCCCL after radical resection. MethodsWe retrospectively analyzed records of 38 patients with PCCCL who were diagnosed at Peking Union Medical College Hospital between January 1989 and September 2010, with a long-term follow up to January 2015, to determine their clinical characteristics and postoperative survival. The data were compared with 400 patients received radical hepatectomy for common type hepatocellular carcinoma (CHCC) during the study period. ResultsPCCCL tumors were smaller than those of CHCC (P < 0.001) and the incidence of vascular invasion of tumors in PCCCL group was significantly lower than that in CHCC (P = 0.029). The 1-, 3-, and 5-year overall survival (OS) for PCCCL patients were 94.6%, 67.3%, and 58.5%, respectively; 1-, 3-, and 5-year disease-free survival (DFS) were 89.2%, 54.1%, and 48.6%, respectively. Both OS and DFS were significantly better for PCCCL patients than for CHCC (P = 0.039 and 0.044). Cox modeling showed high Edmondson grade to be the only independent predictive factor for survival of PCCCL patients, which were different from those of CHCC. ConclusionsPCCCL is a less malignant subtype of HCC than CHCC, patients with PCCCL likely have later intrahepatic recurrences and a better prognosis. Edmondson grade predicts survival of patients with PCCCL after curative resection; those with higher Edmondson grades may require more careful follow-up and aggressive post-hepatectomy therapy.

Background: The aim of this study is to investigate effects of liver resection on albumin binding function in patients with and without cirrhosis.Methods: An observational study was performed on 42 patients with cirrhosis and hepatocellular carcinoma (HCC), and 17 patients without cirrhosis diagnosed with hepatic cavernous hemangioma, all of whom underwent tumor resection. Control group consisted of 50 healthy volunteers. Albumin metal ion binding capacity was assayed as ischemia-modified albumin transformed (IMAT, equal to 1-IMA), and albumin fatty acid binding strength was also tested. All indicators were measured 1 day before and 1, 3, 7 days after surgery.Results: Preoperative IMAT was significantly higher in healthy volunteers than cirrhotic patients (P=0.02), but not than non-cirrhotic patients (P=0.79). Following surgery, a prolonged and sharp reduction was observed in cirrhotic patients; whereas, in non-cirrhotic patients, the result rose sooner and faster. Albumin fatty acid binding strength in both operated groups decreased for the first 3 days after hepatectomy, then both increased to preoperative levels by day 7. Albumin fatty acid binding strength was higher in noncirrhotic than cirrhotic patients at all time points.Conclusions: This is the first study to show that albumin binding function decreases following liver resection in patients with and without cirrhosis. It is more objective than albumin concentration and less affected by albumin infusion. It may be an important indicator of liver function.

AIM:To investigate whether the use of continuous Pringle maneuver (PM) adversely impacts the outcome of patients with hepatocellular carcinoma (HCC).METHODS:From January 1989 to January 2011, 586 HCC patients who underwent curative resection in Peking Union Medical College Hospital were identified from the database. Continuous PM was performed in 290 patients (PM group), including 163 patients with a hepatic inflow occlusion time of <15 min (PM-1 group) and 127 with 15-30 min (PM-2 group). An additional 296 patients underwent partial hepatectomy without inflow occlusion (occlusion-free, OF group).RESULTS:The PM group showed less estimated blood loss during hepatectomy than the OF group (P = 0.005) and the two groups experienced similar incidence of perioperative complications. There were no significant differences in either overall survival or disease-free survival (DFS) between the PM and OF groups (P = 0.117 and 0.291, respectively), and between the PM-1 and PM-2 groups (P = 0.344 and 0.103, respectively). Hepatic inflow occlusion and occlusion time were not independent risk factors for OS or DFS.CONCLUSIONS:Continuous PM effectively reduces intraoperative bleeding and does not adversely impact the outcomes of HCC patients. It remains a valuable tool in hepatic resection, even difficult, complicated resections requiring prolonged clamping times.

BACKGROUND:Detection of circulating cell-free DNA (cfDNA) has potential clinical value for assessing tumor biology in patients with hepatocellular carcinoma (HCC), yet many traditional assays lack robustness. This study was the first to apply a high-throughput sequencing platform to detect tumor-associated mutations in HCC from circulating tumor-derived DNA (ctDNA) and to evaluate the utility and feasibility of this approach.METHODS:Using the MiSeq™ system, plasma and matched tumor DNA samples were analyzed for hotspot mutations in the TERT, CTNNB1, and TP53 genes that had been verified as the most prevalent mutations in HCC. We compared tumor and plasma data and prospectively investigated the association between significant mutations detected in ctDNA and the patients' clinical outcomes.RESULTS:In 41 patients, we detected tumor-associated mutations for HCC in 8 (19.5%) plasma samples. Among them, one showed a tumor-associated mutation in ctDNA but not in the tumor tissue which we used to detect. We also found that ctDNA with mutations could be detected more easily in patients who suffered vascular invasion (P=0.041) and predicted a shorter recurrence-free survival time (P<0.001). There was no relationship between detectable mutations and concentration of cfDNA (P=0.818).CONCLUSIONS:The results of our study suggest that tumor-associated mutations detected in plasma are associated with vascular invasion and might be used to predict a shorter recurrence-free survival time for HCC patients. This kind of biomarker can overcome the limitations of tumor heterogeneity. Moreover, the diagnostic performance is improved if multiple mutations in different genes are combined.