Multicenter evaluation of the safety and efficacy of selective internal radiation therapy with yttrium-90 resin microspheres in Taiwan: data from the RESIN registry.

BACKGROUND AND AIM: The REgistry of Selective Internal radiation therapy in AsiaNs (RESIN) was a multicenter, single-arm, prospective, observational study of 90Y resin microspheres in patients with hepatocellular carcinoma (HCC) or metastatic colorectal cancer (mCRC) from Taiwan. RESIN is the first real-life clinical study of this therapy in an Asian cohort. Study objectives were to evaluate the safety and efficacy of 90Y resin microspheres. METHODS: Adults with HCC or mCRC scheduled to receive SIRT with 90Y resin microspheres were included. Primary endpoints were best overall response rate (ORR), adverse events, and changes from baseline in liver function. Secondary efficacy endpoints included overall survival (OS). RESULTS: Of 107 enrolled patients, 83 had HCC, and 24 had mCRC. ORR was 55.41% (HCC) and 33.33% (mCRC). Of 58 HCC patients with 6-month post-SIRT data, 13.79% (n = 8) had resection, transplantation, transarterial chemoembolization, or radiofrequency ablation as the result of down-staging or down-sizing of their lesions. One hundred and ten treatment emergent adverse events (TEAEs) were reported in 51 patients, and five serious adverse events (SAEs) were reported in five patients. The most frequent TEAEs were abdominal pain, nausea and decreased appetite (HCC), and abdominal pain, decreased appetite, fatigue, and vomiting (mCRC). Two deaths due to SAEs (probably related to SIRT) were reported, both in patients with extensive HCC, active hepatitis infection, and other comorbidities. Median OS was 24.07 (HCC) and 12.66 (mCRC) months. CONCLUSIONS: Safety and efficacy outcomes with the routine use of SIRT with 90Y resin microspheres in Taiwan are consistent with published data.

Automated liver volumetry and hepatic steatosis quantification with magnetic resonance imaging proton density fat fraction.

BACKGROUND: Preoperative imaging evaluation of liver volume and hepatic steatosis for the donor affects transplantation outcomes. However, computed tomography (CT) for liver volumetry and magnetic resonance spectroscopy (MRS) for hepatic steatosis are time consuming. Therefore, we investigated the correlation of automated 3D-multi-echo-Dixon sequence magnetic resonance imaging (ME-Dixon MRI) and its derived proton density fat fraction (MRI-PDFF) with CT liver volumetry and MRS hepatic steatosis measurements in living liver donors. METHODS: This retrospective cross-sectional study was conducted from December 2017 to November 2022. We enrolled donors who received a dynamic CT scan and an MRI exam within 2 days. First, the CT volumetry was processed semiautomatically using commercial software, and ME-Dixon MRI volumetry was automatically measured using an embedded sequence. Next, the signal intensity of MRI-PDFF volumetric data was correlated with MRS as the gold standard. RESULTS: We included the 165 living donors. The total liver volume of ME-Dixon MRI was significantly correlated with CT (r = 0.913, p < 0.001). The fat percentage measured using MRI-PDFF revealed a strong correlation between automatic segmental volume and MRS (r = 0.705, p < 0.001). Furthermore, the hepatic steatosis group (MRS ≥5%) had a strong correlation than the non-hepatic steatosis group (MRS <5%) in both volumetric (r = 0.906 vs. r = 0.887) and fat fraction analysis (r = 0.779 vs. r = 0.338). CONCLUSION: Automated ME-Dixon MRI liver volumetry and MRI-PDFF were strongly correlated with CT liver volumetry and MRS hepatic steatosis measurements, especially in donors with hepatic steatosis.

Longitudinal analysis of liver transplant candidates for hepatocellular carcinoma in a single center.

BACKGROUND: Wailitst lost is an critical issue and we investigated the long-term effect of insufficient liver functional reserve at liver transplantation evaluation on waitlist outcomes in patients with hepatocellular carcinoma (HCC). METHODS: Clinical data of patients with HCC waitlisted for liver transplantation were retrospectively collected from a single hospital cohort during the period from 2014 to 2021. Parameters of liver reserve, including cirrhosis, Child-Pugh grade, and Model for End-Stage Liver Disease (MELD) scores, were analyzed for patient survival, after adjustment for tumor factors. RESULTS: Of 292 eligible patients, 94.2% had cirrhosis, 55.8% had Child-Pugh grade B or C, and the median MELD score was 13.2. The median follow-up time was 2.2 years, with a dropout rate of 62.7%. Eighty-nine candidates (30.5%) eventually received liver transplant, including 67 from live donors. The estimated 1-year mortality rate reached 40.6% in 203 patients who remained on the waitlist without receiving a transplant, of whom 143 died. Most deaths were attributed to liver failure (37.1%) and cancer death (35.7%). After we adjusted for tumor confounders, including alpha fetoprotein, primary HCC stage, tumor number at evaluation, and sequential cancer treatment before and while waiting, hazard ratios (HRs) for patient survival were 1.69 (95% confidence interval, 1.18-2.41) for cirrhotic stage B or C, 1.07 (1.04-1.10) for MELD scores, and 1.14 (1.04-1.25) for tumor size at transplant evaluation. Transplantation was a protective disease modifier with adjusted HR 0.22 (0.14-0.33). CONCLUSION: Insufficient liver functional reserve poses more risk than expected to liver transplant waitlist outcomes with HCC.

Risk factors, patterns, and outcome predictors of late recurrence in patients with hepatocellular carcinoma after curative resection: A large cohort study with long-term follow-up results.

BACKGROUND: Late recurrence of hepatocellular carcinoma after curative resection significantly influences long-term patient survival outcomes, and yet it remains understudied. This study aims to explore the risk factors and patterns of late recurrence and predictors of subsequent outcome. METHODS: This single-center retrospective study analyzed 1,701 consecutive patients who achieved a disease-free survival period exceeding 2 years after curative resection for hepatocellular carcinoma between 2001 and 2018. Univariate and multivariate analyses of factors associated with late recurrence and death after recurrence were conducted using Cox's models. RESULTS: The mean age of patients was 60.2 years, with 76.8% being male. During a median follow-up of 8.1 years, 653 patients (38.4%) experienced late recurrence, with median time to recurrence being 4.0 years (interquartile range, 2.7-6.0). Factors such as age >60, chronic hepatitis C, cirrhosis, high albumin-bilirubin grade, absence of family history, multiple tumors, satellite nodules, alpha-fetoprotein levels <400 ng/mL, and minor hepatic resection were identified as risk factors for late recurrence. Among patients with late recurrence, 131 (20.1%) underwent surgical treatment, 272 (41.7%) received radiofrequency ablation, and 27 (4.1%) exhibited extrahepatic lesions. A higher-high albumin-bilirubin grade, recurrent tumor >3 cm, and nonsurgical treatment emerged as predictors of death after late recurrence. CONCLUSION: Over one-third of patients who remain disease-free for more than 2 years postresection will experience late recurrence during subsequent follow-up. For 2-year disease-free survivors, risk factors for late recurrence differ from early recurrence. Treating underlying hepatitis is of paramount importance, given its association with both the risk of late recurrence and survival outcomes post-recurrence.

HBV DNA Integration into Telomerase or MLL4 Genes and TERT Promoter Point Mutation as Three Independent Signatures in Subgrouping HBV-Related HCC with Distinct Features.

Introduction: A set of genetic mutations to classify hepatocellular carcinoma (HCC) useful to clinical studies is an unmet need. Hepatitis B virus-related HCC (HBV-HCC) harbors a unique genetic mutation, namely, the HBV integration, among other somatic endogenous gene mutations. We explored a combination of HBV DNA integrations and common somatic mutations to classify HBV-HCC by using a capture-sequencing platform. Methods: A total of 153 HBV-HCCs after surgical resection were subjected to capture sequencing to identify HBV integrations and three common somatic mutations in genomes. Three mutually exclusive mutations, HBV DNA integration into the TERT promoter, HBV DNA integration into MLL4, or TERT promoter point mutation, were identified in HBV-HCC. Results: They were used to classify HBV-HCCs into four groups: G1 with HBV-TERT integration (25.5%); G2 with HBV-MLL4 integration (10.5%); G3 with TERT promoter mutation (30.1%); and G4 without these three mutations (34.0%). Clinically, G3 has the highest male-to-female ratio, cirrhosis rate, and associated with higher early recurrence and mortality after resection, but G4 has the best outcome. Transcriptomic analysis revealed a grouping different from the published ones and G2 with an active immune profile related to immune checkpoint inhibitor response. Analysis of integrated HBV DNA provided clues for HBV genotype and variants in carcinogenesis of different HCC subgroup. This new classification was also validated in another independent cohort. Conclusion: A simple and robust genetic classification was developed to aid in understanding HBV-HCC and in harmonizing clinical studies.

Human liver afferent and efferent nerves revealed by 3-D/Airyscan super-resolution imaging.

Neural regulation of hepatic metabolism has long been recognized. However, the detailed afferent and efferent innervation of the human liver has not been systematically characterized. This is largely due to the liver's high lipid and pigment contents, causing false-negative (light scattering and absorption) and false-positive (autofluorescence) results in in-depth fluorescence imaging. Here, to avoid the artifacts in three-dimensional (3-D) liver neurohistology, we embed the bleached human liver in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution imaging. Importantly, using the paired substance P (SP, sensory marker) and PGP9.5 (pan-neuronal marker) labeling, we detect the sensory nerves in the portal space, featuring the SP+ varicosities in the PGP9.5+ nerve bundles/fibers, confirming the afferent liver innervation. Also, using the tyrosine hydroxylase (TH, sympathetic marker) labeling, we identify 1) condensed TH+ sympathetic nerves in the portal space, 2) extension of sympathetic nerves from the portal to the intralobular space, in which the TH+ nerve density is 2.6 ± 0.7-fold higher than that of the intralobular space in the human pancreas, and 3) the TH+ nerve fibers and varicosities contacting the ballooning cells, implicating potential sympathetic influence on hepatocytes with macrovesicular fatty change. Finally, using the vesicular acetylcholine transporter (VAChT, parasympathetic marker), PGP9.5, and CK19 (epithelial marker) labeling with panoramic-to-Airyscan super-resolution imaging, we detect and confirm the parasympathetic innervation of the septal bile duct. Overall, our labeling and 3-D/Airyscan imaging approach reveal the hepatic sensory (afferent) and sympathetic and parasympathetic (efferent) innervation, establishing a clinically related setting for high-resolution 3-D liver neurohistology.NEW & NOTEWORTHY We embed the human liver (vs. pancreas, positive control) in the high-refractive-index polymer for tissue clearing and antifade 3-D/Airyscan super-resolution neurohistology. The pancreas-liver comparison reveals: 1) sensory nerves in the hepatoportal space; 2) intralobular sympathetic innervation, including the nerve fibers and varicosities contacting the ballooning hepatocytes; and 3) parasympathetic innervation of the septal bile duct. Our results highlight the sensitivity and resolving power of 3-D/Airyscan super-resolution imaging in human liver neurohistology.

Comparison of CT and gadoxetic acid-enhanced MRI with liver imaging reporting and data system to assess liver tumors before resection.

BACKGROUND/PURPOSE: Hepatocellular carcinoma (HCC) can be noninvasively diagnosed through dynamic computed tomography (CT) and magnetic resonance imaging (MRI). We compared the diagnostic performance of CT and gadoxetic acid-enhanced MRI (EOB-MRI) in categorizing tumors by using the 2018 version of the Liver Imaging Reporting And Data System (LI-RADS v2018) and assessing liver tumors before resection. METHODS: Data from a prospective cohort from October 2011 to March 2019 on 106 hepatic tumors in 96 patients with suspected malignancy were included in this study. We performed preoperative CT and EOB-MRI, and reviewed these images retrospectively. Ninety-seven tumors from 87 patients were pathologically diagnosed as HCC, and nine tumors were non-HCC. The clinical data, imaging characteristics, diagnostic performance, and outcomes of CT and EOB-MRI were analyzed and compared. RESULTS: EOB-MRI had more favorable diagnostic performance (area under curve: 0.920 vs. 0.868) and significantly higher sensitivity (86.87% vs. 69.70%, p = 0.005) than did CT. However, the specificity of EOB-MRI did not differ from that of CT (88.89% vs. 88.89%, p > 0.999). Fourteen (14.5%) patients with pathologically verified HCC had lesions categorized as LI-RADS 4 through CT and as LI-RADS 5 through EOB-MRI. Patients with EOB-MRI-categorized but not CT-categorized LI-RADS 5 lesions had significantly longer overall survival than did those with LI-RADS 4 lesions (p < 0.001). CONCLUSION: EOB-MRI had higher sensitivity than did CT in diagnosing HCC. Patients with EOB-MRI-categorized LI-RADS 5 lesions had more favorable outcomes than did those with LI-RADS 4 lesions after liver resection.

Computed Tomography-Defined Sarcopenia in Outcomes of Patients with Unresectable Hepatocellular Carcinoma Undergoing Radioembolization: Assessment with Total Abdominal, Psoas, and Paraspinal Muscles.

Introduction: Sarcopenia is an adverse prognostic factor in patients with liver cirrhosis and hepatocellular carcinoma (HCC). Image-based sarcopenia assessment allows a standardized method to assess abdominal skeletal muscle. However, which is an index muscle for sarcopenia remains unclear. Therefore, we investigated whether sarcopenia defined according to different muscle groups with computed tomography (CT) scans can predict the prognosis of HCC after radioembolization. Methods: In this retrospective study, we analyzed patients who underwent radioembolization for unresectable HCC between January 2010 and December 2019. Before treatment, the total abdominal muscle (TAM), psoas muscle (PM), and paraspinal muscle (PS) areas were evaluated using a single CT slice at the third lumbar vertebra. In previous studies, sarcopenia was determined using the TAM, PM, and PS after stratifying by sex. Finally, we investigated each muscle-defined sarcopenia to decide whether or not it can serve as a prognostic factor for overall survival (OS). Results: We included 92 patients (74 men and 18 women). TAM, PM, and PS areas were significantly higher in the men than in the women (all p < 0.05). The patients with sarcopenia defined using PM, but not TAM and PS, exhibited significantly poorer OS than those without sarcopenia (median 15.3 vs. 23.8 months, p = 0.034, 0.821, and 0.341, respectively). After adjustment for clinical variables, such as body mass index, liver function, alpha-fetoprotein level, clinical staging, treatment response, and posttreatment curative therapy, PM-defined sarcopenia (hazard ratio: 1.899, 95% confidence interval: 1.087-3.315) remained an independent predictor for the poor OS. Conclusion: CT-assessed sarcopenia defined using PM was an independent prognostic factor for the poorer prognosis of unresectable HCC after radioembolization.

Cone-beam computed tomography image-guided percutaneous microwave ablation for lung nodules in a hybrid operating room: an initial experience.

OBJECTIVES: The experience of thermal ablation of lung lesions is limited, especially performing the procedure under localisation by cone-beam CT in the hybrid operation room (HOR). Here, we present the experience of microwave ablation (MWA) of lung nodules in the HOR. METHODS: We reviewed patients who underwent image-guide percutaneous MWA for lung nodules in the HOR under general anaesthesia between July 2020 and July 2022. The workflow in the HOR including the pre-procedure preparation, anaesthesia consideration, operation methods, and postoperative care was clearly described. RESULTS: Forty lesions in 33 patients who underwent MWA under general anaesthesia (GA) in the HOR were analysed. Twenty-seven patients had a single pulmonary nodule, and the remaining six patients had multiple nodules. The median procedure time was 41.0 min, and the median ablation time per lesion was 6.75 min. The median global operation room time was 115.0 min. The median total dose area product was 14881 µGym2. The median ablation volume was 111.6 cm3. All patients were discharged from the hospital with a median postoperative stay of 1 day. Four patients had pneumothorax, two patients had pleural effusion during the first month of outpatient follow-up, and one patient reported intercostal neuralgia during the 3-month follow-up. CONCLUSIONS: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if we follow the workflow provided. The procedure provides an alternative to managing pulmonary nodules in patients. CLINICAL RELEVANCE STATEMENT: Thermal ablation of pulmonary nodules under GA in the HOR can be performed safely and efficiently if the provided workflow is followed. KEY POINTS: • We tested the feasibility of microwave ablation of lung lesions performed in a hybrid operating room. • To this end, we provide a description of microwave ablation of the lung under cone-beam CT localisation. • We describe a workflow by which ablation of the pulmonary nodule can be performed safely under general anaesthesia.

Hepatitis C treatment and long-term outcome of patients with hepatocellular carcinoma after resection.

BACKGROUND AND AIM: This study aimed to investigate the survival outcomes of antiviral agents (direct-acting antivirals [DAAs] or interferon [IFN]) in patients with hepatitis C virus who underwent liver resection for primary hepatocellular carcinoma. METHODS: This retrospective single-center study included 247 patients, between 2013 and 2020, being treated with DAAs (n = 93), IFN (n = 73), or no treatment (n = 81). Overall survival (OS), recurrence-free survival (RFS), and risk factors were analyzed. RESULTS: After a median follow-up time of 50.4 months, the rates of 5-year OS and RFS in the IFN, DAA, and no treatment groups were 91.5% and 55.4%, 87.2% and 39.8%, and 60.9% and 26.7%, respectively. One hundred and twenty-eight (51.6%) patients developed recurrence; recurrence was mostly (86.7%) intrahepatic, and 58 (23.4%) developed early recurrence, most of which received no antiviral treatment. The OS and RFS were similar between patients who received antiviral treatment before (50.0%) and after surgery, but longer survival was observed in patients achieving sustained virologic response. In multivariate analysis, antiviral treatment was protective for OS (hazard ratio [HR] 0.475, 95% confidence interval [CI]: 0.242-0.933) with significance but not RFS, in contrast to microvascular invasion (OS HR 3.389, 95% CI: 1.637-7.017; RFS HR 2.594, 95% CI: 1.520-4.008). In competing risk analysis, DAAs (subdistribution HR 0.086, 95% CI: 0.007-0.991) were protective against hepatic decompensation events but not recurrence events. CONCLUSION: In patients with hepatitis C virus, antiviral treatment suggested OS benefit for primary hepatocellular carcinoma after resection, and DAAs might be protective against hepatic decompensation. Following adjustment for oncological factors, IFN and DAA treatment was not significantly advantageous relative to the other.

Detrimental effects of fresh frozen plasma transfusions on postoperative outcomes in patients undergoing liver resection for hepatocellular carcinoma.

BACKGROUND: Perioperative fresh frozen plasma (FFP) is commonly transfused to patients undergoing liver resection for hepatocellular carcinoma (HCC), but its impacts in this population remain unknown. This study aimed to investigate the association of perioperative FFP transfusion with short-term and long-term outcomes in these patients. METHODS: We retrospectively identified and retrieved clinical data for HCC patients undergoing liver resection between March, 2007 and December, 2016. Study outcomes included postoperative bacterial infection, extended length of stay (LOS) and survival. Propensity score (PS) matching was used to determine the association of FFP transfusion with each outcome. RESULTS: A total of 1427 patients were included, and 245 of them received perioperative FFP transfusions (17.2%). Patients received perioperative FFP transfusions were older, underwent liver resection in the earlier time period, and had more extensive resection, poorer clinical conditions, and higher proportions of receiving other blood components. Perioperative FFP transfusion was associated with higher odds of both postoperative bacterial infection (OR = 1.77, p = 0.020) and extended LOS (OR = 1.93, p=<0.001), and the results remained similar after PS-matching. However, perioperative FFP transfusion did not significantly affect survival in these patients (HR = 1.17, p = 0.185). A potential association of postoperative FFP transfusions and poorer 5-year but not overall survival was observed in a subgroup of patients with low postoperative albumin levels after PS-matching. CONCLUSION: Perioperative FFP transfusions were associated with poorer short-term postoperative outcomes in HCC patients undergoing liver resection, including postoperative bacterial infection and extended LOS. Reducing perioperative FFP transfusions has the potential to improve their postoperative outcomes.

Viral Status and Treatment Efficacy in Recurrent Hepatocellular Carcinoma After Primary Resection.

BACKGROUND: The impact of viral background on long-term effectiveness of different treatment modalities for recurrent hepatocellular carcinoma (HCC) was not fully analyzed. METHOD: Consecutive 726 patients who developed intrahepatic recurrence after primary hepatectomy for HCC between 2008 and 2015 were retrospectively studied. Post-recurrence survival (PRS) and rerecurrence-free survival (R-RFS) and risk factors were analyzed. RESULTS: After a median follow-up period of 56 months, the 5-year PRS rates of the patients who underwent rehepatectomy, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) were 79.4%, 83.0%, and 54.6%, respectively. The treatment benefit for PRS was consistently observed in patients with hepatitis B virus (HBV) and non-B, non-C subgroups, but not hepatitis C virus (HCV). For patients with late recurrence of HCC, R-RFS was superior in HBV subgroup and HCV subgroup which received antiviral treatment (compared to naïve HCV subgroup). Survival difference triaged by viral status was lost in the counterpart with early recurrence. Overall, RFA improved PRS and R-RFS in patients receiving antiviral treatment. CONCLUSION: To achieve long-term survival after HCC recurrence, rehepatectomy and RFA were comparably effective, particularly among those with HBV. Antiviral treatment complemented survivals of patients with HCV after RFA, particularly in late first recurrence.

Effects of transjugular intrahepatic portosystemic shunt on abdominal muscle mass in patients with decompensated cirrhosis.

BACKGROUND: Sarcopenia is a common finding in patients with decompensated cirrhosis without effective therapy. We aimed to examine whether a transjugular portosystemic shunt (TIPS) could improve the abdominal muscle mass assessed by cross-sectional images in patients with decompensated cirrhosis and to investigate the association of imaging-defined sarcopenia with the prognosis of such patients. METHODS: In this retrospective observational study, we enrolled 25 Decompensated cirrhosis patients aged >20 who received TIPS for the control of variceal bleeding or refractory ascites between April 2008 and April 2021. All of them underwent preoperative computed tomography or magnetic resonance imaging, which was used to determine psoas muscle (PM) and paraspinal muscle (PS) indices at the third lumbar vertebra. First, we compared baseline muscle mass with muscle mass at 6 and 12 months after TIPS placement and analyzed PM- and PS-defined sarcopenia to predict mortality. RESULTS: Among 25 patients, 20 (80.0%) and 12 (48.0%) had PM- and PS-defined sarcopenia, respectively, at baseline. In total, 16 and 8 patients were followed up for 6 and 12 months, respectively. All imaging-based muscle measurements performed 12 months after TIPS placement were significantly greater than the baseline measurements (all p < 0.05). Unlike patients with PS-defined sarcopenia (p = 0.529), patients with PM-defined sarcopenia had poorer survival than did patients without (p = 0.036). CONCLUSION: PM mass in patients with decompensated cirrhosis may increase by 6 or 12 months after TIPS placement and imply a better prognosis. Patients with preoperative PM-defined sarcopenia may suggest poorer survival.

Hepatitis B Virus DNA Integration Drives Carcinogenesis and Provides a New Biomarker for HBV-related HCC.

Hepatitis B virus (HBV) DNA integration is an incidental event in the virus replication cycle and occurs in less than 1% of infected hepatocytes during viral infection. However, HBV DNA is present in the genome of approximately 90% of HBV-related HCCs and is the most common somatic mutation. Whole genome sequencing of liver tissues from chronic hepatitis B patients showed integration occurring at random positions in human chromosomes; however, in the genomes of HBV-related HCC patients, there are integration hotspots. Both the enrichment of the HBV-integration proportion in HCC and the emergence of integration hotspots suggested a strong positive selection of HBV-integrated hepatocytes to progress to HCC. The activation of HBV integration hotspot genes, such as telomerase (TERT) or histone methyltransferase (MLL4/KMT2B), resembles insertional mutagenesis by oncogenic animal retroviruses. These candidate oncogenic genes might shed new light on HBV-related HCC biology and become targets for new cancer therapies. Finally, the HBV integrations in individual HCC contain unique sequences at the junctions, such as virus-host chimera DNA (vh-DNA) presumably being a signature molecule for individual HCC. HBV integration may thus provide a new cell-free tumor DNA biomarker to monitor residual HCC after curative therapies or to track the development of de novo HCC.

Longitudinal analysis of transplant candidates with primary sclerosing cholangitis in an Asian liver transplant center.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a rare disease in Asia, and few studies have investigated the disease in this ethnicity, particularly in wait-listed patients for liver transplantation (LT). We aimed to investigate the prognostic factors and outcomes of wait-listed patients with PSC in an Asian transplant center. METHODS: Survival was retrospectively analyzed. RESULTS: Eighteen (10 male and 8 female) wait-listed patients with PSC, with a median age at diagnosis of 44.5 years, were included. Compared with men, women had significantly higher aspartate aminotransferase to platelet ratio index scores (3.28 vs. 1.13; P = 0.012) and bilirubin levels (7.68 vs. 4.03 mg/dl; P = 0.043) and more often presented with decompensating events, including ascites [5 (63%) vs. 1 (10%); P = 0.043] and splenomegaly [8 (100%) vs. 4 (40%); P = 0.013]. Compared with the non-LT group, the LT group exhibited a superior survival rate for women ( P = 0.004) but not for men. In the univariable analysis, significant risk factors associated with overall survival included malignancies with a hazard ratio (95% confidence interval) of 5.53 (1.00-30.51) and esophageal varices (EV) [4.18 (1.05-16.61)], whereas female gender [25.00 (1.49-500.00)], LT [0.09 (0.01-0.80)] and EV [39.03 (2.92-521.96)] were indicated in the multivariable analysis. CONCLUSIONS: For Asian wait-listed patients with PSC, EV and female gender were the risk factors related to overall survival, and LT was the protective factor. Our experiences suggested that LT brings more benefits in female patients. Strategies are needed to provide equivalent transplant benefits.

Interval dynamics of transplantability for hepatocellular carcinoma after primary curative resection: risk factors for nontransplantable recurrence.

BACKGROUND: To investigate the changes in transplantability between primary and recurrent Hepatocellular carcinoma (HCC) after hepatic resection (HR) and the risk factors for nontransplantable recurrence (NTR). METHODS: Consecutive 3122 patients who received HR for primary HCC between 2001 and 2019 were analyzed for changes in transplantability. Predictors of survival and NTR were evaluated using a competing risk analysis. RESULTS: After a median follow-up of 78.3 months, the 5-year overall survival rate was 82.6%. Also, 58.2% of them developed recurrence after a median of 45.6 months. Recurrence occurred in 1205 and 611 patients with primary transplantable and nontransplantable HCC, respectively, of whom 26.1% and 63.2%, respectively, had NTR. Tumor diameter >3 cm [subdistribution hazard ratios (95% CI), 2.00 (1.62-2.48)], major resection [1.20 (1.00-1.43)], pathological grade >2 [1.28 (1.07-1.52)], microvascular invasion [1.74 (1.45-2.08)], and early recurrence (<1 year) [9.22 (7.83-10.87)] were associated with NTR. The overall transplantable pool increased from 72.3% to 77.5%. CONCLUSION: Microvascular invasion and early recurrence were risk factors for NTR. Nonetheless, the transplantable pool increased after HR, 41.8% of the patients had no recurrence and may not require liver transplantation. If the patient's liver function is acceptable, HR should be considered the treatment of choice for HCC.

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results.

Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

Different clinical and genetic features of Alagille patients with progressive disease versus a jaundice-free course.

Background and Aim: Alagille syndrome (ALGS) is a multisystem disorder with variable clinical courses. This study investigated the clinical and genetic features of ALGS patients with different outcomes and analyzed the liver pathology at liver transplantation (LT) compared with that in biliary atresia (BA). Methods: We report the clinical characteristics, outcomes, and genetic mutations of 25 children with ALGS followed for a median of 7.3 years. Patients were classified into (i) jaundice-free (JF) group (resolving jaundice after 2 years of age); (ii) progressive disease (PD) group (persistent jaundice or progressive cholestasis). In addition, we analyzed the explant liver in 10 ALGS patients compared with 20 age-matched BA patients at the time of LT. Results: Nine patients (36%) in the JF group had a favorable outcome, with longer native liver survival than patients with PD (n = 16, P < 0.001). Fourteen of the PD group patients received LT or died. We identified 18 different JAG1 mutations in 22 patients. Three unrelated probands in the JF group had the same de novo mutation in JAG1, c.2122-2125delCAGT. Compared with BA children, ALGS patients had lower METAVIR scores in liver pathology, higher serum albumin levels, and lower weight-for-age z-scores when receiving LT. Conclusion: One-third of ALGS patients had JF and a favorable course. Children with ALGS presenting with persistent jaundice beyond 2 years of age should be cautioned for poor prognosis. ALGS patients tend to have a lesser extent of cirrhosis, and more growth problems than BA patients at the time of LT.

Single-stage augmented fluoroscopic bronchoscopy localization and thoracoscopic resection of small pulmonary nodules in a hybrid operating room.

OBJECTIVES: Hybrid operating rooms (HOR) have been increasingly used for image-guided lung surgery, and most surgical teams have used percutaneous localization for small pulmonary nodules. We evaluated the feasibility and safety of augmented fluoroscopic bronchoscopy localization under endotracheal tube intubation general anaesthesia followed by thoracoscopic surgery as a single-stage procedure in ab HOR. METHODS: We retrospectively reviewed clinical records of patients who underwent single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery in an HOR between August 2020 and March 2022. RESULTS: Single-stage localization and resection were performed for 85 nodules in 74 patients. The median nodule size was 8 mm [interquartile range (IQR), 6-9 mm], and the median distance from the pleural space was 10.9 mm (IQR, 8-20 mm). All nodules were identifiable on cone-beam computed tomography images and marked transbronchially with indigo carmine dye (median markers per lesion: 3); microcoils were placed for deep margins in 16 patients. The median localization time was 30 min (IQR 23-42 min), and the median fluoroscopy duration was 3.3 min (IQR 2.2-5.3 min). The median radiation exposure (expressed as the dose area product) was 4303.6 µGym2 (IQR 2879.5-6268.7 µGym2). All nodules were successfully marked and resected, and the median global operating room time was 178.5 min (IQR 153.5-204 min). There were no localization-related complications, and the median length of postoperative stay was 1 day (IQR, 1-2 days). CONCLUSIONS: Single-stage augmented fluoroscopic bronchoscopy localization under general anaesthesia followed by thoracoscopic surgery was feasible and safe.

Delayed Hepatocellular Carcinoma Recurrence After Liver Transplantation: Comprehensive Clinical Characterization of Case Series.

Purpose: Liver transplantation (LT) is the definite curative treatment for hepatocellular carcinoma (HCC), but recurrence can occur even under stringent criteria. "Delayed" HCC recurrence (>3 years after LT) is not common. Here, we present the clinical features of patients who developed delayed HCC recurrence after LT. Patients and Methods: We reviewed the data of eligible patients from February 1999 to December 2020 from medical records. Results: From among 195 (17%) HCC patients who received LT, 34 experienced HCC recurrence, with 5 (15%) delayed recurrence. These five explant tumors were staged T1b-T2, graded II-III, with two vascular invasion and four beyond the Milan criteria. The median time to recurrence was 6.1 years, with the longest interval being nearly 18 years. Recurrence patterns included two extrahepatic, one intrahepatic, and two mixed extrahepatic and intrahepatic recurrences. A drastic increase in serum alpha-fetoprotein levels was observed in four cases 1 year before recurrence. Management of recurrence included locoregional (surgssical resection in three, radiotherapy in three, transarterial chemoembolization in one, radiofrequency ablation in one) and systemic sorafenib use in three. Two patients died within 12-18 months, one died within 18-24 months, and two are still alive until the end of the study, with respective 13.5- and 16.5-month survival. Conclusion: Delayed HCC recurrence could occur over 10 years. Therefore, continual surveillance for recurrence is justified, but biomarkers and intervals or intensities specific for delayed recurrence are not validated, which warrants further validation to facilitate personalized medical care.