Simulation training of laparoscopic biliary-enteric anastomosis with a three-dimensional-printed model leads to better skill transfer: a randomized controlled trial.

AIM: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. METHODS: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. RESULTS: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups ( P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups ( P =0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups ( P =0.004). CONCLUSIONS: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques.

Comparison of short-term outcomes between robotic and laparoscopic distal gastrectomy performed by the same surgical team during the same period.

Objective: To evaluate the short-term outcomes of laparoscopic distal gastrectomy and robotic distal gastrectomy performed during the same period. Methods: This study enrolled 46 cases of laparoscopic distal gastrectomy and 67 cases of robotic distal gastrectomy that were performed by a single surgeon between April 2020 to October 2021. Baseline characteristics and short-term outcomes of these two groups were then compared. Moreover, the robotic distal gastrectomy group was further divided into two subgroups according to the learning curve. Finally, the baseline characteristics and short-term outcomes of both subgroups were compared with the laparoscopic group, respectively. Results: The baseline characteristics and short-term outcomes of the LDG group and RDG group were comparable. In contrast, the operation time in the laparoscopic group was significantly shorter than that in the early experience robotic group (191.3 ± 37.6 VS 225.1 ± 49, P=0.001). However, the operation time (191.3 ± 37.6 VS 185.3 ± 25.3, P=0.434) was comparable between the laparoscopic group and the late experience robotic group. Likewise, the bleeding volume was comparable between the laparoscopic and early experience robotic groups. However, bleeding volume was significantly lower in the late experience robotic group compared to that in the laparoscopic group (37.5 ± 18.8 VS 49.2 ± 29.0, P=0.049). Conclusions: With surgeons stepping into the stable stage of the robotic learning curve, RDG showed a comparable operation time and lower volume of blood loss compared with LDG. Collectively, our study supports the application of robotic distal gastrectomy in patients diagnosed with gastric cancer.

Wedge resection versus segment IVb and V resection of the liver for T2 gallbladder cancer: a systematic review and meta-analysis.

Objectives: Although guidelines recommend extended cholecystectomy for T2 gallbladder cancer (GBC), the optimal hepatectomy strategy remains controversial. The study aims to compare the prognosis of T2 GBC patients who underwent wedge resection (WR) versus segment IVb and V resection (SR) of the liver. Methods: A specific search of online databases was performed from May 2001 to February 2023. The postoperative efficacy outcomes were synthesized and meta-analyses were conducted. Results: A total of 9 studies involving 2,086 (SR = 627, WR = 1,459) patients were included in the study. The primary outcomes included disease-free survival (DFS) and overall survival (OS). For DFS, the 1-year DFS was statistically higher in patients undergoing SR than WR [risk ratio (RR) = 1.07, 95% confidence interval (CI) = 1.02-1.13, P = 0.007]. The 3-year DFS (P = 0.95), 5-year DFS (P = 0.77), and hazard ratio (HR) of DFS (P = 0.72) were similar between the two groups. However, the 3-year OS was significantly lower in patients who underwent SR than WR [RR = 0.90, 95% CI = 0.82-0.99, P = 0.03]. Moreover, SR had a higher hazard HR of OS [HR = 1.33, 95% CI = 1.01-1.75, P = 0.04]. No significant difference was found in 1-year (P = 0.32) and 5-year (P = 0.9) OS. For secondary outcomes, patients who received SR tended to develop postoperative complications (POC) [RR = 1.90, 95% CI = 1.00-3.60, P = 0.05]. In addition, no significant differences in intrahepatic recurrence (P = 0.12) were observed. Conclusions: In conclusion, SR can improve the prognosis of T2 GBC patients in DFS. In contrast to WR, the high HR and complications associated with SR cannot be neglected. Therefore, surgeons should evaluate the condition of the patients and take their surgical skills into account when selecting SR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier, CRD42022362974.

Cytoskeleton remodeling mediated by circRNA-YBX1 phase separation suppresses the metastasis of liver cancer.

Metastasis, especially intrahepatic, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously, we reported that HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as an important regulator of various cellular processes and has been implicated in cancer progression. Here, we uncovered a nuclear circRNA, circASH2, which is preferentially lost in HCC tissues and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was posttranscriptionally suppressed. Such regulation is based on messenger RNA (mRNA)/precursormRNA splicing and degradation process. Furthermore, liquid-liquid phase separation of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a tumor-suppressive circRNA and, more importantly, uncovered a fine regulation mechanism for HCC progression.

Clinical utility of resected pancreatic volume ratio calculation for predicting postoperative new-onset diabetes mellitus after distal pancreatectomy-a propensity-matched analysis.

Background: Limited literature is available on new-onset diabetes mellitus (NODM) after distal pancreatectomy. This study aimed to investigate the correlation between surgery-related factors and the incidence of NODM after distal pancreatectomy. Methods: Patients were divided into the NODM-positive or NODM-negative group according to the diagnosis of NODM. After propensity score matching, the correlation between operation-related factors and the incidence of NODM was analyzed. The diagnostic threshold for predicting NODM was determined using the receiver operating characteristic (ROC) curve and the Youden index. Results: No significant correlation was observed between the NODM incidence after distal pancreatectomy and operative blood loss, spleen preservation, surgical method (open or laparoscopy), postoperative ALB and HB (first day after surgery), and postoperative pathology. However, a significant correlation was found between the NODM incidence and the postoperative pancreatic volume or the resected pancreatic volume ratio. Resected pancreatic volume ratio was identified as a predictive risk factor for NODM. Youden index of the ROC curve was 0.548, with a cut off value of 32.05% for resected pancreatic volume ratio. The sensitivity and specificity of the cut off values were 0.952 and 0.595, respectively. Conclusions: This study demonstrated that the volume ratio of pancreatic resection is a risk factor for the incidence of NODM after distal pancreatectomy. This can be used to predict the incidence of NODM and may have further clinical applications.

Recent advances in the role of exosomes in liver fibrosis.

BACKGROUND AND AIM: We aim to summarize the current status of research on the role of exosomes in liver fibrosis. METHODS: A review of the relevant literature was performed and the key findings were presented. RESULTS: Most studies focused on the role of exosomes derived from mesenchymal stem cells, other types of stem cells, and liver resident cells including hepatocytes, cholangiocytes, and hepatic stellate cells in liver fibrosis. Exosomes have been reported to play an essential role in the inactivation or activation of hepatic stellate cells through the delivery of non-coding RNAs and proteins. In recent years, this exosome cargo has become a research hotspot. CONCLUSIONS: Recent studies have indicated the potential therapeutic benefit of exosomes in liver fibrosis.

Adhesive cryogel particles for bridging confined and irregular tissue defects.

BACKGROUND: Reconstruction of damaged tissues requires both surface hemostasis and tissue bridging. Tissues with damage resulting from physical trauma or surgical treatments may have arbitrary surface topographies, making tissue bridging challenging. METHODS: This study proposes a tissue adhesive in the form of adhesive cryogel particles (ACPs) made from chitosan, acrylic acid, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The adhesion performance was examined by the 180-degree peel test to a collection of tissues including porcine heart, intestine, liver, muscle, and stomach. Cytotoxicity of ACPs was evaluated by cell proliferation of human normal liver cells (LO2) and human intestinal epithelial cells (Caco-2). The degree of inflammation and biodegradability were examined in dorsal subcutaneous rat models. The ability of ACPs to bridge irregular tissue defects was assessed using porcine heart, liver, and kidney as the ex vivo models. Furthermore, a model of repairing liver rupture in rats and an intestinal anastomosis in rabbits were established to verify the effectiveness, biocompatibility, and applicability in clinical surgery. RESULTS: ACPs are applicable to confined and irregular tissue defects, such as deep herringbone grooves in the parenchyma organs and annular sections in the cavernous organs. ACPs formed tough adhesion between tissues [(670.9 ± 50.1) J/m2 for the heart, (607.6 ± 30.0) J/m2 for the intestine, (473.7 ± 37.0) J/m2 for the liver, (186.1 ± 13.3) J/m2 for muscle, and (579.3 ± 32.3) J/m2 for the stomach]. ACPs showed considerable cytocompatibility in vitro study, with a high level of cell viability for 3 d [(98.8 ± 1.2) % for LO2 and (98.3 ± 1.6) % for Caco-2]. It has comparable inflammation repair in a ruptured rat liver (P = 0.58 compared with suture closure), the same with intestinal anastomosis in rabbits (P = 0.40 compared with suture anastomosis). Additionally, ACPs-based intestinal anastomosis (less than 30 s) was remarkably faster than the conventional suturing process (more than 10 min). When ACPs degrade after surgery, the tissues heal across the adhesion interface. CONCLUSIONS: ACPs are promising as the adhesive for clinical operations and battlefield rescue, with the capability to bridge irregular tissue defects rapidly.

Evaluation of PD-L1 as a biomarker for immunotherapy for hepatocellular carcinoma: systematic review and meta-analysis.

Aim: To determine if PD-L1 can be used as a biomarker to predict the efficacy of anti-PD-1/PD-L1 inhibitors in hepatocellular carcinoma (HCC). Methods: Relevant studies from a specific search of the four databases from October 2014 to December 2022 were included in this meta-analysis. Results: Higher PD-L1 expression levels were associated with a higher objective response rate (ORR). Higher PD-L1 expression levels on tumor cells and tumor proportion score were associated with higher ORR. PD-L1 was capable of predicting the effectiveness of nivolumab. Dako 28-8 is a promising assay for HCC. Conclusion: PD-L1 is a predictive biomarker for ORR in HCC. Tumor proportion score and PD-L1 expression levels on tumor cells are potential scoring algorithms.

Clinically, liver cancer patients with high PD-L1 levels may not benefit from immunotherapy. Conversely, some patients with low PD-L1 level can benefit from it. Therefore, the concept of PD-L1 as a predictive indicator in liver cancer is defective. Whether PD-L1 can serve as an indicator in liver cancer patients receiving immunotherapy needs urgent confirmation. In this work, we evaluated the feasibility of PD-L1 as a prognostic biomarker for immunotherapy. The results suggested that high expression of PD-L1 by tumor cells rather than tumor tissue was correlated with better prognosis.

The Learning Curve Study of Robotic Distal Gastrectomy: an Analysis of Outcomes of the First 67 Consecutive Cases at a High-Volume Gastric Center.

BACKGROUND: Robotic distal gastrectomy (RDG) is performed increasingly; a sound understanding of the learning curve in robotic distal gastrectomy has taken on great importance METHODS: Data on the 67 RDG cases were collected from one surgeon with rich experience in laparoscopic gastrectomy. Cumulative sum (CUSUM) analysis based on operative time was used to identify inflexion points. RESULTS: Thirty-five cases, on average, were needed to complete operation time-learning curve sufficiently. A reduction in surgical time was observed in the last 32 cases compared with the first 35 cases (185.3 ± 25.3 min vs. 225.1 ± 49 min, P < 0.01). CONCLUSIONS: Surgeons with extensive laparoscopic experience can master robotic distal gastrectomy techniques after some training.

Formative objective structured clinical examination with immediate feedback improves surgical clerks' self-confidence and clinical competence.

OBJECTIVE: Clerkship is crucial for fourth-year medical students before entering the clinical environment. However, lack of confidence impairs clerks' performance during the clinical rotation. We assess the impact of formative Objective Structured Clinical Examination (OSCE) with immediate feedback on surgical clerks' self-confidence and clinical competence. METHODS: This is a prospective randomized controlled study. Thirty-eight fourth-year medical students starting their surgical clerkship were randomly divided into the control group (n = 19) and the OSCE group (n = 19), where an extra 6-station formative OSCE was given prior to the surgical rotation with immediate feedback on the participant's performance. Self-confidence assessment (SCA) was collected from each participant before, right after the formative OSCE and one month later. Clinical competence was assessed using a mini-clinical evaluation exercise (mini-CEX) with a case of acute abdominal pain and direct observation of procedural skills (DOPS) with incision and suture one month later. RESULTS: The SCAs were significantly improved in the OSCE group right after the training, and a month later, compared to the control group. The mini-CEX score was significantly higher in the OSCE group compared to the control group, but not the DOPS score of incision and suture. CONCLUSION: The formative OSCE with immediate feedback could significantly enhance surgical clerks' self-confidence and their clinical competence when taking the history, performing the physical examination, and in clinical reasoning; however, the formative OSCE did not improve their dexterity in performing the procedural skills.

A study of simulation training in laparoscopic bilioenteric anastomosis on a 3D-printed dry lab model.

BACKGROUND: There are few studies on simulation training in laparoscopic bilioenteric anastomosis. There is also a lack of mature and reliable training models for bilioenteric anastomosis. In this study, we aimed to assess a feasible training model for bilioenteric anastomosis. Surgeons can improve their surgical ability by performing laparoscopic bilioenteric anastomosis on this model through repeated training. METHOD: The original articles related to simulation training in surgical anastomosis were identified from January 2000 to November 2021 in the Clarivate Analytics Web of Science Core Collection database. We conducted a bibliometric analysis based on the country of these publications and the type of anastomosis. A 3D-printed bilioenteric anastomosis model was applied in this study. Baseline data of 15 surgeons (5 surgeons of Attendings, 5 surgeons of Fellows, and 5 surgeons of Residents) were collected. The bilioenteric anastomosis data, including the operation time and operation score, were recorded and analyzed. A study of the learning curve was also performed for further assessment. RESULT: Surgeons at different levels of experience exhibited different levels of performance in conducting laparoscopic bilioenteric anastomosis on this model. Experienced surgeons completed their first training session in a shorter time and obtained a higher surgical score. In turn, repeated training significantly shortened the time of laparoscopic bilioenteric anastomosis for each trainer and improved the surgical score. Surgeons with different levels of experience needed different numbers of cases to reach the stable period of the learning curve. Experienced surgeons were able to reach a proficient level through fewer training cases. CONCLUSION: A suitable biliary-enteric anastomosis model can help surgeons conduct simulation training and provide experience and skill accumulation for future real operations. Our training model performed well in this study and can effectively accomplish this goal.

Simulation training of laparoscopic pancreaticojejunostomy and stepwise training program on a 3D-printed model.

AIM: Laparoscopic pancreaticojejunostomy is among the most difficult and high-risk operations. Surgeons with low or moderate seniority rarely are allowed to perform this surgery in clinics. Therefore, there is an urgent need to develop a reliable simulation training model focused on laparoscopic pancreaticojejunostomy and an effective stepwise training program. METHODS: Surgeons with different working experiences or exposure to different training programs at Sir Run Run Shaw Hospital were divided into four groups. Each was required to perform laparoscopic pancreaticojejunostomy using a designed three-dimensional dry lab model. All surgeons' baseline characteristics and surgical performance, including operation time and score, were recorded and analysed. The authenticity of the model was evaluated by four senior surgeons. RESULTS: The surgeon group with higher seniority had an older average age, longer working time, and had completed more laparoscopic cholecystectomy and laparoscopic common bile duct exploration procedures. Meanwhile, the surgeon group with higher seniority presented better operation performance, including shorter operation time and higher operation score in their initial simulation training. Resident surgeons who underwent stepwise training with the laparoscopic biliary-enteric anastomosis training program showed better initial performance than resident surgeons who underwent stepwise training with the laparoscopic basic suture training program. After repeated training, the surgeons showed improved surgical performance. CONCLUSION: Our pancreaticojejunostomy model showed a good degree of discernibility, as surgeons with more experience performed better with the model for their initial simulation training in laparoscopic pancreaticojejunostomy. Stepwise training of the laparoscopic biliary-enteric anastomosis training program helped surgeons obtain a better initial performance, and repeated simulation training on this model improved the surgeon's operative performance.

Enhanced Recovery Care vs. Traditional Care in Laparoscopic Hepatectomy: A Systematic Review and Meta-Analysis.

Background: Enhanced recovery care could alleviate surgical stress and accelerate the recovery rates of patients. Previous studies showed the benefits of enhanced recovery after surgery program in liver surgery, but the exact role in laparoscopic hepatectomy is still unclear. Aim: We aimed to perform a meta-analysis to evaluate the safety and efficacy of enhanced recovery after a surgery program in laparoscopic hepatectomy. Methods: The relative studies from a specific search of PUBMED, EMBASE, OVID, and Cochrane database from June 2008 to February 2022 were selected and included in this meta-analysis. The primary outcomes included length of hospital stay, duration to functional recovery, and overall postoperative complication rate. The secondary outcomes included operative time, intraoperative blood loss, cost of hospitalization, readmission rate, Grade I complication rate, and Grade II-V complication rate. Results: A total of six studies with 643 patients [enhanced recovery care (n = 274) vs. traditional care (n = 369)] were eligible for analysis. These comprised three randomized controlled trials and three retrospective studies. Enhanced recovery care group was associated with decreased hospital stay [standard mean difference (SMD) = -0.56, 95% confidence interval (CI) = -0.83~-0.28, p < 0.0001], shorter duration to functional recovery (SMD = -1.14, 95% CI = -1.92~-0.37, p = 0.004), and lower cost of hospitalization Mean Difference (MD) = -1,539.62, 95% CI = -1992.85~-1086.39, p < 0.00001). Moreover, a lower overall postoperative complication rate was observed in enhanced recovery care group [Risk ratio (RR) = 0.64, 95% CI = 0.51~0.80, p < 0.0001] as well as lower Grade II-V complication rate (RR = 0.55, 95% CI = 0.38~0.80, p = 0.002), while there was no significant difference in intraoperative blood loss (MD = -65.75, 95% CI = -158.47~26.97, p = 0.16), operative time (MD = -5.44, 95% CI = -43.46~32.58, p = 0.78), intraoperative blood transfusion rate [Odds ratio (OR) = 0.71, 95% CI = 0.41~1.22, p = 0.22], and Grade I complication rate (RR = 0.73, 95% CI = 0.53~1.03, p = 0.07). Conclusion: Enhanced recovery care in laparoscopic hepatectomy should be recommended, because it is not only safe and effective, but also can accelerate the postoperative recovery and lighten the financial burden of patients.

Biologic therapy for Crohn's disease over the last 3 decades.

BACKGROUND: Despite the overload of publications on Crohn's disease (CD), no comprehensive analysis of biologic therapy for CD has been reported. AIM: To determine knowledge gaps and identify areas of interest of biologic therapy for CD. METHODS: The top 100 highest-cited original articles were identified from January 1991 to December 2020 in the Clarivate Analytics Web of Science Core Collection database. We conducted a bibliometric analysis of biologic therapy for CD based on total citations, summarized the bibliographic information of the articles related to CD biologic therapy, and explored the research hotspots. RESULTS: The top 100 highest-cited original articles were identified with total citations ranging from 307 to 2978. The 2000s (Period II, n = 66) yielded the most influential original articles and saw the most dramatic growth. Among the top 10 countries, including 8 European countries and 2 North American countries, the United States (n = 37) and Belgium (n = 20) contributed the most publications. Among the top 10 institutions, the University Hospital Gasthuisberg in Belgium (n = 23), the University of Chicago in the United States (n = 20), and the Mayo Clinic in the United States (n = 17) published the most papers. Regarding authors, Rutgeerts P in Belgium (n = 32), Sandborn WJ in the United States (n = 23), and Feagan BG in Canada (n = 18) published the highest number of studies. The cooperation relationships between the United States and Europe were most frequent. Gastroenterology (impact factor = 22.682) published the most articles on biologic therapy for CD (n = 32) with 17654 total citations. Anti-tumor necrosis factor biologics and monoclonal antibodies were the most studied topics. CONCLUSION: The bibliometric analysis emphasized the key contributions to the development of the specialized field. These data would provide useful research insights into biologic therapy for CD for clinicians and researchers.

Targeting mutant p53 for cancer therapy: direct and indirect strategies.

TP53 is a critical tumor-suppressor gene that is mutated in more than half of all human cancers. Mutations in TP53 not only impair its antitumor activity, but also confer mutant p53 protein oncogenic properties. The p53-targeted therapy approach began with the identification of compounds capable of restoring/reactivating wild-type p53 functions or eliminating mutant p53. Treatments that directly target mutant p53 are extremely structure and drug-species-dependent. Due to the mutation of wild-type p53, multiple survival pathways that are normally maintained by wild-type p53 are disrupted, necessitating the activation of compensatory genes or pathways to promote cancer cell survival. Additionally, because the oncogenic functions of mutant p53 contribute to cancer proliferation and metastasis, targeting the signaling pathways altered by p53 mutation appears to be an attractive strategy. Synthetic lethality implies that while disruption of either gene alone is permissible among two genes with synthetic lethal interactions, complete disruption of both genes results in cell death. Thus, rather than directly targeting p53, exploiting mutant p53 synthetic lethal genes may provide additional therapeutic benefits. Additionally, research progress on the functions of noncoding RNAs has made it clear that disrupting noncoding RNA networks has a favorable antitumor effect, supporting the hypothesis that targeting noncoding RNAs may have potential synthetic lethal effects in cancers with p53 mutations. The purpose of this review is to discuss treatments for cancers with mutant p53 that focus on directly targeting mutant p53, restoring wild-type functions, and exploiting synthetic lethal interactions with mutant p53. Additionally, the possibility of noncoding RNAs acting as synthetic lethal targets for mutant p53 will be discussed.

Artificial intelligence in gastroenterology and hepatology: Status and challenges.

Originally proposed by John McCarthy in 1955, artificial intelligence (AI) has achieved a breakthrough and revolutionized the processing methods of clinical medicine with the increasing workloads of medical records and digital images. Doctors are paying attention to AI technologies for various diseases in the fields of gastroenterology and hepatology. This review will illustrate AI technology procedures for medical image analysis, including data processing, model establishment, and model validation. Furthermore, we will summarize AI applications in endoscopy, radiology, and pathology, such as detecting and evaluating lesions, facilitating treatment, and predicting treatment response and prognosis with excellent model performance. The current challenges for AI in clinical application include potential inherent bias in retrospective studies that requires larger samples for validation, ethics and legal concerns, and the incomprehensibility of the output results. Therefore, doctors and researchers should cooperate to address the current challenges and carry out further investigations to develop more accurate AI tools for improved clinical applications.

Clinical-Radiomic Analysis for Pretreatment Prediction of Objective Response to First Transarterial Chemoembolization in Hepatocellular Carcinoma.

BACKGROUND: The preoperative selection of patients with intermediate-stage hepatocellular carcinoma (HCC) who are likely to have an objective response to first transarterial chemoembolization (TACE) remains challenging. OBJECTIVE: To develop and validate a clinical-radiomic model (CR model) for preoperatively predicting treatment response to first TACE in patients with intermediate-stage HCC. METHODS: A total of 595 patients with intermediate-stage HCC were included in this retrospective study. A tumoral and peritumoral (10 mm) radiomic signature (TPR-signature) was constructed based on 3,404 radiomic features from 4 regions of interest. A predictive CR model based on TPR-signature and clinical factors was developed using multivariate logistic regression. Calibration curves and area under the receiver operating characteristic curves (AUCs) were used to evaluate the model's performance. RESULTS: The final CR model consisted of 5 independent predictors, including TPR-signature (p < 0.001), AFP (p = 0.004), Barcelona Clinic Liver Cancer System Stage B (BCLC B) subclassification (p = 0.01), tumor location (p = 0.039), and arterial hyperenhancement (p = 0.050). The internal and external validation results demonstrated the high-performance level of this model, with internal and external AUCs of 0.94 and 0.90, respectively. In addition, the predicted objective response via the CR model was associated with improved survival in the external validation cohort (hazard ratio: 2.43; 95% confidence interval: 1.60-3.69; p < 0.001). The predicted treatment response also allowed for significant discrimination between the Kaplan-Meier curves of each BCLC B subclassification. CONCLUSIONS: The CR model had an excellent performance in predicting the first TACE response in patients with intermediate-stage HCC and could provide a robust predictive tool to assist with the selection of patients for TACE.

Adjuvant transarterial chemoembolization to sorafenib in unresectable hepatocellular carcinoma: A meta-analysis.

BACKGROUND AND AIM: An increasing number of transarterial chemoembolization (TACE) plus sorafenib combination therapy has been applied for unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether combination therapy is superior to sorafenib monotherapy. Therefore, we aimed to perform a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib for unresectable HCC. METHODS: This meta-analysis was based on the relative outcomes from a specific search of online databases between January 2008 and November 2019, and subgroup analyses were conducted to identify potential predictive factors. RESULTS: A total of 3868 patients (TACE plus sorafenib vs sorafenib, 1181 vs 2687) were identified from nine studies, including one randomized controlled trial and eight retrospective cohort studies. The pooled results revealed that TACE plus sorafenib combination therapy significantly improves overall survival with the combined hazard ratio 0.74 (95% confidence interval [CI] = 0.66-0.84, P < 0.001), time to progression (hazard ratio = 0.73, 95%CI = 0.65-0.82, P < 0.001), and objective response rate (odds ratio = 2.19, 95% CI = 1.31-3.66, P = 0.003). Subgroup analysis indicated that patients who developed macrovascular invasion achieve significantly great overall survival (P for interaction = 0.001) with combination therapy, in contrast to nonmacrovascular invasion patients. In addition, no significant differences in adverse events were observed. CONCLUSION: This meta-analysis demonstrated that TACE plus sorafenib combination therapy is superior to sorafenib monotherapy and should be recommended as an optimal treatment choice for unresectable HCC.

Perioperative outcomes comparing laparoscopic with open repeat liver resection for post-hepatectomy recurrent liver cancer: A systematic review and meta-analysis.

BACKGROUND: Repeat laparoscopic hepatectomy (LRH) offers an option for recurrent tumors in liver remnants following an initial liver resection of recurrent hepatocellular carcinoma (HCC), colorectal liver metastasis (CRLM) and cholangiocellular carcinoma (CCC), showing advantages in some outcomes. The objective of the study was to evaluate the feasibility, safety, and potential benefits of LRH in comparison with repeat open hepatectomy (ORH) for recurrent liver cancer. METHODS: A systematic review was performed in compliance with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) and AMSTAR (Assessing the methodological quality of systematic reviews) guidelines. We performed a systematic search of PubMed, Embase, Cochrane Library, and Web of Science to identify studies that compared LRH with ORH from inception to September 30, 2019. Outcomes of interest included operation time, intraoperative estimated blood loss, length of hospital stay, complication rate, transfusion and R0 resection rate. The protocol was registered with the PROSPERO register of systematic reviews. RESULTS: 10 retrospective observational studies were suitable for this analysis, involving 767 patients with 334 undergoing LRH (43.5%) and 433 undergoing ORH (56.5%). Compared with ORH, LRH had less intraoperative blood loss (SMD = -1.03; 95% CI: 1.48~-0.59, P < 0.001), less overall postoperative complications (OR = 0.40; 95% CI: 0.16-0.99, P = 0.048), less major complications (OR = 0.31, 95% CI: 0.15-0.62, P = 0.001), shorter hospital stay (SMD = -0.98; 95% CI: 1.41~-0.54, P < 0.001) and higher R0 resection rate (OR = 2.30, 95% CI: 1.39-3.81, P = 0.001). It was comparable in operation time (WMD = -7.66; 95% CI: 52.50-37.19, P = 0.738), transfusion rate (OR = 0.33; 95% CI:0.11-1.05, P = 0.060), and mortality (OR = 0.76; 95% CI: 0.27-2.18, P = 0.615) between LRH and ORH. CONCLUSION: Our results indicate that LRH is a safe and effective technique. Benefits, especially less intra-operative blood loss, less complications rate, shorter hospital stay and higher R0 resection, might be offered in the laparoscopic approach.