Pretransplant use of immune checkpoint inhibitors for hepatocellular carcinoma: A multicenter, retrospective cohort study.

Immune checkpoint inhibitors (ICIs) as a downstaging or bridging therapy for liver transplantation (LT) in hepatocellular carcinoma patients are rapidly increasing. However, the evidence about the feasibility and safety of pre-LT ICI therapy is limited and controversial. To this end, a multicenter, retrospective cohort study was conducted in 11 Chinese centers. The results showed that 83 recipients received pre-LT ICI therapy during the study period. The median post-LT follow-up was 8.1 (interquartile range 3.3-14.6) months. During the short follow-up, 23 (27.7%) recipients developed allograft rejection, and 7 of them (30.4%) were diagnosed by liver biopsy. Multivariate logistics regression analysis showed that the time interval between the last administration of ICI therapy and LT (TLAT) ≥ 30 days was an independent protective factor for allograft rejection (odds ratio = 0.096, 95% confidence interval 0.026-0.357; P < .001). Multivariate Cox analysis showed that allograft rejection was an independent risk factor for overall survival (hazard ratio = 9.960, 95% confidence interval 1.006-98.610; P = .043). We conclude that patients who receive a pre-LT ICI therapy with a TLAT shorter than 30 days have a much higher risk of allograft rejection than those with a TLAT longer than 30 days. The presence of rejection episodes might be associated with higher post-LT mortality.

Total Laparoscopic Resection of an Extrahepatic Mucinous Biliary Cystadenoma with Liver Involvement (with Video).

BACKGROUND: Intrahepatic mucinous biliary cystadenoma is rare, and extrahepatic MBC is even rarer. To our knowledge, total laparoscopic resection of an extrahepatic MBC that had extended intrahepatically has never been reported. PATIENTS AND METHODS: A 28-year-old female presented to our hospital with upper abdomen pain. Radiological investigations demonstrated a 7-cm multiloculated cystic lesion arising from the left hepatic bile duct extending to involve the extrahepatic biliary system down to and posterior to the back of the head of pancreas. The entire extrahepatic bile duct was involved, except for the gallbladder. Laparoscopic surgery was carried out using a five-port approach. A gourd-shaped well-defined multiloculated cyst was found extending from the extrahepatic biliary system proximally to involve the left hepatic duct intrahepatically. After cholecystectomy, the gourd-shaped cyst was opened at its narrowest part at the hepatic hilus to facilitate subsequent resectional surgery. The distal sac was dissected to the distal bile duct end at the duodenal wall and transected. The proximal sac was dissected and resected en bloc with the bifurcation of the right/left hepatic ducts, combined with left hepatectomy plus caudate lobectomy. The reconstruction was done by anastomosing the right anterior and posterior sectional bile ducts to a Roux-en-Y jejunal loop. Multiple intraoperative frozen sections demonstrated the lesion to be a benign MBC. RESULTS: The patient was discharged home 12 days after surgery. She was well on follow-up 24 months after surgery. CONCLUSION: Total laparoscopic resection is technically feasible to treat an extrahepatic MBC with intrahepatic extension.

Laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach.

BACKGROUND: With advances in technology, laparoscopic liver resection is widely accepted. Laparoscopic liver resection under hemihepatic vascular inflow occlusion has advantages over the conventional total hepatic inflow occlusion using the Pringle's maneuver, especially in patients with cirrhosis. METHOD: From November 2011 to August 2012, eight consecutive patients underwent laparoscopic liver resection under hemihepatic vascular inflow occlusion using the lowering of hilar plate approach with biliary bougie assistance. RESULTS: The types of liver resection included right hepatectomy (n=1), right posterior sectionectomy (n=1), left hepatectomy and common bile duct exploration (n=1), segment 4b resection (n=1), left lateral sectionectomy (n=2), and wedge resection (n=2). Four patients underwent right and 4 left hemihepatic vascular inflow occlusion. Four patients had cirrhosis. The mean operation time was 176.3 minutes. The mean time taken to achieve hemihepatic vascular inflow occlusion was 24.3 minutes. The mean duration of vascular inflow occlusion was 54.5 minutes. The mean intraoperative blood loss was 361 mL. No patient required blood transfusion. Postoperatively, one patient developed bile leak which healed with conservative treatment. No postoperative liver failure and mortality occurred. The mean hospital stay of the patients was 7 days. CONCLUSION: Our technique of hemihepatic vascular inflow vascular occlusion using the lowering of hilar plate approach was safe, and it improved laparoscopic liver resection by minimizing blood loss during liver parenchymal transection.

Constructing diagnostic signature of serum microRNAs using machine learning for early pan-cancer detection.

BACKGROUND: Cancer is a major public health concern and the second leading cause of death worldwide. Various studies have reported the use of serum microRNAs (miRNAs) as non-invasive biomarkers for cancer detection. However, large-scale pan-cancer studies based on serum miRNAs have been relatively scarce. METHODS: An optimized machine learning workflow, combining least absolute shrinkage and selection operator (LASSO) analyses, recursive feature elimination (RFE), and fourteen kinds of machine learning algorithms, was use to screen out candidate miRNAs from 2540 serum miRNAs and constructed a potent diagnostic signature (Cancer-related Serum miRNA Signatures) for pan-cancer detection, based on a serum miRNA expression dataset of 38,223 samples. RESULT: Cancer-related Serum miRNA Signatures performed well in pan-cancer detection with an area under curve (AUC) of 0.999, 94.51% sensitivity, and 99.49% specificity in the external validation cohort, and represented an acceptable diagnostic performance for identifying early-stage tumors. Furthermore, the ability of multi-classification of tumors by serum miRNAs in pancreatic, colorectal, and biliary tract cancers was lower than that in other cancers, which showed accuracies of 59%, 58.5%, and 28.9%, respectively, indicating that the difference in serum miRNA expression profiles among a small number of tumor subtypes was not as significant as that between cancer samples and non-cancer controls. CONCLUSION: We have developed a serum miRNA signature using machine learning that may be a cost-effective risk tool for pan-cancer detection. Our findings will benefit not only the predictive diagnosis of cancer but also a preventive and more personalized screening plan.

Serum micro-RNAs with mutation-targeted RNA modification: a potent cancer detection tool constructed using an optimized machine learning workflow.

RNA modifications affect fundamental biological processes and diseases and are a research hotspot. Several micro-RNAs (miRNAs) exhibit genetic variant-targeted RNA modifications that can greatly alter their biofunctions and influence their effect on cancer. Therefore, the potential role of these miRNAs in cancer can be implicated in new prevention and treatment strategies. In this study, we determined whether RMvar-related miRNAs were closely associated with tumorigenesis and identified cancer-specific signatures based on these miRNAs with variants targeting RNA modifications using an optimized machine learning workflow. An effective machine learning workflow, combining least absolute shrinkage and selection operator analyses, recursive feature elimination, and nine types of machine learning algorithms, was used to screen candidate miRNAs from 504 serum RMvar-related miRNAs and construct a diagnostic signature for cancer detection based on 43,047 clinical samples (with an area under the curve value of 0.998, specificity of 93.1%, and sensitivity of 99.3% in the validation cohort). This signature demonstrated a satisfactory diagnostic performance for certain cancers and different conditions, including distinguishing early-stage tumors. Our study revealed the close relationship between RMvar-related miRNAs and tumors and proposed an effective cancer screening tool.

Lenvatinib plus drug-eluting bead transarterial chemoembolization with/without hepatic arterial infusion chemotherapy for hepatocellular carcinoma larger than 7 cm with major portal vein tumor thrombosis: a multicenter retrospective cohort study.

BACKGROUND: The management of hepatocellular carcinoma (HCC) with high tumor burden and major portal vein tumor thrombosis (PVTT) remains a great challenge. We aimed to investigate the efficacy and safety of lenvatinib plus drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (Len+DEB-TACE+HAIC) versus lenvatinib plus DEB-TACE (Len+DEB-TACE) for HCC > 7.0 cm accompanied with major PVTT. MATERIALS AND METHODS: This multicenter retrospective cohort study evaluated consecutive patients with HCC (> 7.0 cm) and major PVTT who received Len+DEB-TACE+HAIC (Len+DEB-TACE+HAIC group) or Len+DEB-TACE (Len+DEB-TACE group) between July 2019 and June 2021 from eight institutions in China. Objective response rate (ORR), time to progression (TTP), overall survival (OS), and treatment-related adverse events (TRAEs) were compared between the two groups by propensity score-matching (PSM). RESULTS: A total of 205 patients were included. After PSM, 85-paired patients remained in the study cohorts. Patients in the Len+DEB-TACE+HAIC group had higher ORR (61.2% vs. 34.1%, P < 0.001), longer TTP (median, 9.8 vs. 5.9 months, P < 0.001), and prolonged OS (median, 16.7 vs. 12.5 months, P < 0.001) than those in the Len+DEB-TACE group. The ORR and TTP of both intrahepatic tumor (ORR: 64.7% vs. 36.5%, P < 0.001; median TTP: 10.7 vs. 7.0 months, P < 0.001) and PVTT (ORR: 74.1% vs. 47.1%, P < 0.001; median TTP: 17.4 vs. 7.6 months, P < 0.001) were better in the Len+DEB-TACE+HAIC group than the Len+DEB-TACE group. The frequency of grade 3-4 TRAEs in the Len+DEB-TACE+HAIC group were comparable to those in the Len+DEB-TACE group (38.8% vs. 34.1%, P = 0.524). CONCLUSION: The addition of HAIC to Len+DEB-TACE significantly improved ORR, TTP, and OS over Len+DEB-TACE with an acceptable safety profile for large HCC with major PVTT.

Regorafenib with immunotherapy versus regorafenib alone as second-line treatment for hepatocellular carcinoma: A multicenter real-world study.

INTRODUCTION: Regorafenib remains the standard and widely used second-line strategy for advanced hepatocellular carcinoma (HCC). There is still a lack of large-scale multicenter real-world evidence concerning the concurrent use of regorafenib with immune checkpoint inhibitors (ICI). This study aims to evaluate whether combining regorafenib with ICI provides greater clinical benefit than regorafenib monotherapy as second-line therapy for advanced HCC under real-world circumstances. PATIENTS AND METHODS: The study included 208 patients from five medical facilities. One hundred forty-three patients received regorafenib plus ICI combination therapy, while 65 patients received regorafenib monotherapy. Propensity score matching (PSM) analysis was employed. RESULTS: The regorafenib plus ICI group demonstrated significantly higher objective response rate (24.3% vs. 10.3%, after PSM, p = 0.030) and disease control rate (79.4% vs. 50.0%, after PSM, p < 0.001) compared to the regorafenib monotherapy group based on mRECIST criteria. Median progression-free survival (7.9 vs. 3.2 months, after PSM, p < 0.001) and overall survival (25.6 vs. 16.4 months, p = 0.010, after PSM) were also considerably longer in the regorafenib plus ICI group. The incidence of Grades 3-4 treatment-related adverse events (TRAEs) was marginally greater in the regorafenib plus ICI group than in the regorafenib group (23.8% vs. 20.0%, p = 0.546). Notably, there were no instances of treatment-related mortality or emergence of new TRAEs in any treatment group. CONCLUSION: The combination of regorafenib and ICI shows potential as a viable second-line treatment for advanced HCC, exhibiting favorable efficacy while maintaining a tolerable safety profile in contrast to regorafenib monotherapy.

Preservation of Porcine Donation after Circulatory Death (DCD) Liver by Perfusion and Orthotopic Liver Transplantation.

Conventional static cold storage (SCS) exacerbates ischemic injury in the DCD liver, leading to severe complications for transplant recipients. To address this issue, clinical application of MP technology for donor liver preservation is underway. Simultaneously, efforts are focused on the development of various MP instruments, validated through relevant animal model experiments. Effective large animal trials play a pivotal role in clinical applications. However, challenges persist in the ex vivo preservation of DCD livers and the transplantation procedure in pigs. These hurdles encompass addressing the prolonged preservation of donor livers, conducting viability tests, alleviating ischemic injuries, and shortening the anhepatic phase. The use of a variable temperature-controlled MP device facilitates the prolonged preservation of DCD livers through sequential Dual Hypothermic Oxygenated Machine Perfusion (DHOPE) and Normothermic Machine Perfusion (NMP) modes. This protocol enhances the porcine OLTx model by improving the quality of DCD livers, optimizing the anastomosis technique, and reducing the duration of the anhepatic phase.

Exploration of the methods of establishing the minimum clinical important difference based on anchors and their applications in the quality of life measurement scale QLICP-BR (V2.0) for breast cancer.

Objective: The measurement of the quality of life (QOL) in patients with breast cancer can evaluate the therapeutic effects of medical treatments and help to provide reference for clinical decisions. The minimum clinically important difference (MCID) can be better used in clinical interpretation than the traditional statistical significance. Based on the anchors, a variety of ways including traditional and updated anchor-based methods were used to explore most suitable MCID, so that to find better interpretation on scores of the scale QLICP-BR(V2.0) (Quality of Life Instruments for Cancer Patients-Breast cancer). Methods: According to the investigation data of breast cancer patients before and after treatment, the most relevant indicators in various domains of QLICP-BR (V2.0) was found as an anchor to statistically analyze the value of MCID, and three analysis methods of anchors were used: Traditional anchor-based method, ROC curve method, multiple linear regression model analysis. Anchors are divided into four standards according to the degree of change in the treatment effect: one grade difference (Standard A), at least one grade difference (Standard B), one grade better (Standard C), better (Standard D). The final MCID value is selected from different statistical methods and classification standards that are most suitable for clinicians to use. Results: Using Q29 of the EORTC QLQ-C30 as an anchor has the highest correlation with each domain of QLICP. The order of magnitude of MCID values among the four standard groups is: standard A< Standard C< Standard B< Standard D. The MCID value obtained by the ROC curve method is the most stable and is least affected by the sample size, and the MCID value obtained by the multiple linear regression model is the least. After comparisons and discussions, Standard C in the multiple linear regression model is used to determine the final MCID, which is the closest to other methods. After integer the MCID values of Physical domain (PHD), Psychological domain (PSD), Social domain (SOD), Common symptoms and side effect domain (SSD), Core/general module (CGD), Specific domain (SPD), Total score(TOT) can be taken as 15,10, 10, 11, 10, 9 and 9, respectively. Conclusion: In the evaluation of the QOL of breast cancer patients, although the results of MCID values produced by different methods are different, the results are relatively close. The anchor-based methods make the results of MCID more clinically interpretable by introducing clinical variables, and clinicians and researchers can choose the appropriate method according to the research purpose.

Health-related quality of life and its influencing factors in patients with breast cancer based on the scale QLICP-BR.

Breast cancer is the most common cancer and the leading cause of cancer death among females worldwide. During the past 15 years, quality of life (QOL) has become an important aspect of breast cancer treatment. The purpose of this study was to evaluate QOL of breast cancer patients in China, and investigate its associations with sociodemographic and clinical variables. A cross-sectional study was conducted in 246 breast cancer patients in China. Recruited patients were surveyed for QOL using the QOL instruments for cancer patients-breast cancer QLICP-BR (V2.0). We assessed the associations between potential influencing factors and QOL using multiple linear regression models. The general mean QOL score for our population was 70.24 with SD = 8.70. Results indicated that medical insurance, drinking history, alkaline phosphatase, serum chloride ion level, serum calcium ion level, serum phosphorus ion level, mean corpuscular volume, mean corpuscular hemoglobin, red cell volume distribution width and platelet had significant associations with QOL of breast cancer patients. Our results emphasized that many factors are affecting QOL of breast cancer patients, which may provide a reference for targeted management or intervention strategies of breast cancer patients to improve their QOL.

Effects of Preservation of Donor Liver Gastroduodenal Artery on Post-Transplant Biliary Complications in 187 Liver Transplant Recipients: A Retrospective Study.

BACKGROUND This retrospective study aimed to evaluate the effects of preservation of the donor liver gastroduodenal artery on post-transplant biliary complications in 187 liver transplant recipients. MATERIAL AND METHODS The clinical data of 187 liver transplantation recipients were retrospectively analyzed. Recipients were divided into conventional and modified groups. The technical point of the modified group is to preserve at least 2 cm of the distal gastroduodenal artery, and pay special attention to preserve the superior pancreaticoduodenal artery to ensure the distal blood supply to the common bile duct. RESULTS The modified group had significantly shorter operative time (7.17 vs 7.98) h (P<0.001) and less intraoperative blood loss (2715.40 vs 3434.93) ml (P=0.003) than the conventional group. The incidence of postoperative biliary complications (including anastomotic biliary leakage, ischemic bile duct stenosis, and anastomotic bile duct stenosis) in the modified group (4/114, 4.1%) was significantly lower (15/73, 20.5%) (P<0.001). There was no significant difference in the intraoperative cold and warm ischemia time and postoperative hospital stay length between the 2 groups. In addition, there was no significant difference in the effect of cardiac-death and brain-death sources on perioperative biliary complications, while the peak postoperative transaminase and total bilirubin were higher in patients receiving the donor liver of cardiac death (P<0.05). CONCLUSIONS Preserving the integrity of the donor gastroduodenal artery and surrounding tissue is beneficial to protect the blood supply of the extrahepatic bile duct, and can reduce the incidence of biliary complications.

Nomograms for predicting the recurrence probability and recurrence-free survival in patients with hepatocellular carcinoma after conversion hepatectomy based on hepatic arterial infusion chemotherapy: a multicenter, retrospective study.

BACKGROUND: This study aimed to establish and validate nomograms to predict the probability of recurrence and recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) after conversion hepatectomy based on hepatic arterial infusion chemotherapy (HAIC). METHODS: Nomograms were constructed using data from a retrospective study of 214 consecutive patients treated with HAIC-based conversion liver resection between January 2016 and July 2020. Nomograms predicting the probability of tumor recurrence and RFS were established based on predictors selected by multivariate regression analysis. Predictive accuracy and discriminative ability of the nomogram were examined. Bootstrap method was used for internal validation. External validation was performed using cohorts ( n =128) from three other centers. RESULTS: Recurrence rates in the primary and external validation cohorts were 63.6 and 45.3%, respectively. Nomograms incorporating clinicopathological features of tumor recurrence and RFS were generated. Concordance index (C-index) scores of the nomograms for predicting recurrence probability and RFS were 0.822 (95% CI, 0.703-0.858) and 0.769 (95% CI, 0.731-0.814) in the primary cohort, and 0.802 (95% CI, 0.726-0.878) and 0.777 (95% CI, 0.719-0.835) in the external validation cohort, respectively. Calibration curves indicated good agreement between the nomograms and actual observations. Moreover, the nomograms outperformed the commonly used staging systems. Patients with low risk, stratified by the median nomogram scores had better RFS (low risk vs. high risk, 36.5 vs. 5.2 months, P <0.001). The external validation cohort supported these findings. CONCLUSIONS: The presented nomograms showed favorable accuracy for predicting recurrence probability and RFS in HCC patients treated with HAIC-based conversion hepatectomy. Identifying risk factors and estimating tumor recurrence may help clinicians in the decision-making process regarding adjuvant therapies for patients with HCC, which eventually achieves better oncological outcomes.

Hepatic Arterial Infusion Chemotherapy Plus Lenvatinib and Tislelizumab with or Without Transhepatic Arterial Embolization for Unresectable Hepatocellular Carcinoma with Portal Vein Tumor Thrombus and High Tumor Burden: A Multicenter Retrospective Study.

Purpose: The current therapeutic strategies for high-risk, unresectable hepatocellular carcinoma (HCC) patients demonstrate suboptimal outcomes. This study aimed to assess the clinical efficacy of the combined approach of hepatic arterial infusion chemotherapy (HAIC), lenvatinib, and tislelizumab, either with or without transhepatic arterial embolization (TAE), in managing HCC patients with portal vein tumor thrombus (PVTT) and significant tumor load. Patients and Methods: In this multicenter retrospective study, we analyzed patients diagnosed with primary, unresectable HCC presenting with PVTT and substantial tumor load who had undergone treatment with HAIC, lenvatinib, and tislelizumab, with or without TAE (referred to as the THLP or HLP group), between January 2019 and February 2022 across four medical centers in China. The outcomes included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS). Results: The study cohort comprised 100 patients, 50 each in the THLP and HLP groups. The THLP group demonstrated a significantly superior ORR (72% vs 52%, P=0.039). However, both groups exhibited comparable DCR (88% vs 76%, P=0.118), as assessed by the modified response evaluation criteria in solid tumors. The median OS and PFS for the entire cohort were 12.5 months (95% CI, 10.9-14.8) and 5.0 months (95% CI, 4.2-5.4), respectively. The THLP group exhibited a significantly extended OS (median, 14.1 vs 11.3 months, P=0.041) and PFS (median, 5.6 vs 4.4 months, P=0.037) in comparison to the HLP group. The most frequently reported treatment-related adverse events included abdominal pain and nausea, both reported by 59% of patients. Conclusion: The combination of HAIC, lenvatinib, tislelizumab, and TAE was feasible in HCC patients with PVTT and high tumor burden, with tolerable safety.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Mating Systems of Single Families and Population Genetic Diversity of Endangered Ormosia hosiei in South China.

Ormosia hosiei is a tree species native to China that has been extensively used for ornamental and furniture purposes due to its valued timber. The mating system has substantial impact on genetic diversity and structure of plant natural population. Such information should be considered when planning tree planting for forest restoration. Here we used 12 microsatellite markers and described the mating system of single families and the population genetic diversity of O. hosiei. A high level of genetic diversity was observed in both adults and progenies, although slight differences existed among populations and their progenies, with the expected heterozygosity ranging from 0.763 to 0.794. Overall, O. hosiei displayed a predominantly outcrossed mating. The estimate of multi-locus outcrossing rate (tm) was high with low variations among families, ranged from 0.997 to 1.000. The value of tm-ts, ranged from 0.000 to 0.139, indicated that biparental inbreeding occurred in progenies. Therefore, to obtain a reasonable genetic representation of native tree species and prevent problems associated with inbreeding depression, we suggested effective in situ conservation by replanting seedlings, but seedling production for restoration purposes may require a much larger sampling effort than is currently used. Moreover, it is necessary to conduct further multiple population and multi-year experiments to verify our conclusions.

Establishing Minimal Clinically Important Differences for the Quality of Life Instrument in Patients With Breast Cancer QLICP-BR (V2.0) Based on Anchor-Based and Distribution-Based Methods.

Objective: To determine the minimal clinically important differences (MCIDs) for the breast cancer scale QLICP-BR (V2.0) among the Quality of Life Instruments system for cancer patients (QLICP), which consist of the general module of 32 items classifying into 4 domains and the specific module of 10 items. Methods: According to the scoring rule of QLICP-BR (V2.0), the scores of each domain and the overall scale were calculated. The MCIDs of this scale were established by anchor-based and distribution-based methods. The anchor method used the Q29 item in the EORTC QLQ-C30 scale as anchors and defined the treatment effectiveness of the anchor-based method using criteria A (one level improvement after treatment) and B (at least one level improvement after treatment), while methods of effect size (ES), standard error of measurement (SEM), and reliability change index (RCI) were used in distribution-based methods. Results: Using the anchor-based method, according to standard A, the MCIDs of the physical domain (PHD), psychological domain (PSD), social domain (SOD), common symptoms and side effect domain (SSD), core/general module (CGD), specific domain (SPD), and the total score (TOT) were 16.24, 11.37, 11.31, 12.07, 11.49, 10.69, and 11.23 respectively; according to standard B, the MCIDs of PHD, PSD, SOD, SSD, CGD, SPD, and TOT were 18.88, 15.14, 14.10, 14.50, 13.93, 12.17, and 14.23 respectively. In the distribution-based MCID study, when ES = 0.8, the MCID values of each domain and the total score of the scale were 9.14, 10.34, 8.34, 10.54, 6.79, 9.73, and 6.96 respectively. The MCIDs calculated when a SEM of 1.96 was used as the intermediary index were 8.38, 11.04, 8.67, 10.00, 7.44, 9.83, and 7.81. The MCIDs calculated when a RCI of 1.96 was used as the intermediary index were 11.84, 15.61, 12.27, 14.14, 10.52, 13.90, and 11.05. Additionally, the MCID value calculated by the two standards of the anchor method was similar to 0.8 ES, 1.96 SEM, and 1.96 RCI. Conclusion: Using the anchor-based method, 0.8ES, 1.96SEM, and 1.96RCI have a better effect on the minimal clinically important difference of breast cancer scale and were recommended to be the preferred methods for establishing MCID.

Development and Validation of the Breast Cancer Scale QLICP-BR V2.0 Based on Classical Test Theory and Generalizability Theory.

Objective: The aim of this study was to develop and validate the breast cancer scale among the system of quality-of-life instruments for cancer patients (QLICP-BR V2.0). Methods: Programmed decision procedures and theories on instrument development were applied to develop QLICP-BR V2.0. A total of 246 breast cancer inpatients were investigated using QLICP-BR V2.0 from hospital admission until discharge. The reliability, validity, and responsiveness of the QLICP-BR V2.0 scale were evaluated by using the classical test theory combined with the generalizability theory (GT), including correlation analysis, multi-trait scaling analysis, factor analyses, t-tests, and also multivariate generalizability theory analysis. Results: The test-retest reliability of the total scale is 0.79, the Cronbach coefficient is 0.85, and the intra-class correlations coefficient is 0.88. The item-domain correlation analysis showed that the correlation coefficient between items and their own domain is greater than that with other domains except of item GSO4. The exploratory factor analysis showed that three principal components are obtained in the specific module. The outcome of the factor analysis coincides substantially with our theoretical conception. The score difference of each domain of the scale and the total scale before and after treatment is statistically significant (P < 0.05), with the standardized response mean of the total scale being 0.61. According to GT, the generalization coefficient of the scores in the 5 domains is between 0.626 and 0.768, and the reliability index is between 0.557 and 0.695. Conclusion: QLICP-BR V2.0 exhibited reasonable degrees of validity, reliability, and responsiveness according to classical test and the generalizability theory. The number of items in the scale is appropriate.

Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial.

PURPOSE: In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population. METHODS: In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment. RESULTS: Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related. CONCLUSION: FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

Lenvatinib plus TACE with or without pembrolizumab for the treatment of initially unresectable hepatocellular carcinoma harbouring PD-L1 expression: a retrospective study.

PURPOSE: The aim of this retrospective study was to compare the clinical outcomes of pembrolizumab-lenvatinib-transarterial chemoembolization (TACE) versus lenvatinib-TACE sequential therapy in selected populations of Chinese patients with initially unresectable hepatocellular carcinoma (uHCC) harbouring programmed cell death ligand-1 (PD-L1) expression. METHODS: Consecutive patients with initial PD-L1-positive uHCC who received pembrolizumab-lenvatinib-TACE or lenvatinib-TACE sequential therapy were retrospectively identified from three medical institutions during 2016-2020. The primary endpoints included the rate of conversion therapy, defined as converting initially uHCC to hepatectomy, overall survival (OS), and progression-free survival (PFS); secondary endpoint was the frequency of key adverse events (AEs). RESULTS: In total, 220 consecutively recruited patients were retrospectively reviewed, 78 of whom were ineligible according to the current criteria, leaving 142 patients [pembrolizumab-lenvatinib-TACE: n = 70, median age 58 years (range 36-69) and lenvatinib-TACE: n = 72, 57 years (35-68)] who were eligible for the study. The median duration of follow-up was 27 months [95% confidence interval (CI), 26.3-28.7 months]. At the last follow-up, the rate of conversion therapy was 25.7% in the pembrolizumab-lenvatinib-TACE group and 11.1% in the lenvatinib-TACE group (p = 0.025). The median OS was 18.1 months (95% CI 16.5-20.7) in the pembrolizumab-lenvatinib-TACE group versus 14.1 months (95% CI 12.2-16.9) in the lenvatinib-TACE group [hazard ratio (HR) 0.56, 95% CI 0.38-0.83; p = 0.004]. A distinct difference in the median PFS interval between the groups was detected [9.2 months (95% CI 7.1-10.4) in the pembrolizumab-lenvatinib-TACE group vs. 5.5 months (95% CI 3.9-6.6) in the lenvatinib-TACE group (HR 0.60; 95% CI 0.39-0.91; p = 0.006)]. The rates of the key AEs assessed, which were hypertension, nausea, and rash, were higher in the pembrolizumab-lenvatinib-TACE group than in the lenvatinib-TACE group (all p < 0.05). CONCLUSION: Among the selected populations of patients with initial PD-L1-positive uHCC, pembrolizumab-lenvatinib-TACE sequential therapy may have promising antitumour activity, with an acceptable conversion rate and a well-characterized safety profile.

Joint Transcriptomic and Metabolic Analysis of Flavonoids in Cyclocarya paliurus Leaves.

Flavonoids are a class of commonly occurring natural compounds in the plant kingdom with various biological activities. This study compares the content of flavonoids in Cyclocarya paliurus at different developmental stages to better inform the selection of the optimal picking period. Thus, we analyzed the transcriptome and metabolome of C. paliurus at different developmental stages. The transcriptome analysis revealed 44 genes involved in the biosynthesis of flavonoids in C. paliurus, with 10 differentially expressed genes across the four different developmental stages. The metabolites were separated and identified by a combination of chromatography and mass spectrometry, followed by multi-reaction monitoring mode analysis of triple quadrupole mass spectrometry for complete metabolite quantification. In the flavonoid synthesis pathway, a total of 137 differential flavonoids were detected. The joint transcriptome and metabolome analysis showed that the expression trends in differential metabolites and genes were significantly related. Four MYB transcription factors and two bHLH transcription factors that are closely related to flavonoid biosynthesis were identified. The regulation network of flavonoid biosynthesis in C. paliurus was thus established, providing guidance for follow-up research.