Feasibility and safety of robotic liver resection for huge (≥10 cm) hepatocellular carcinoma in a single centre: A propensity score-matched single-surgeon study.

BACKGROUND: The applicability of robot-assisted resection for huge hepatocellular carcinoma (HCC) of ≥10 cm remains contentious with limited available data. METHODS: This retrospective analysis involved 337 patients who underwent robotic liver resection for HCC by a single surgeon. Propensity score matching (PSM) was employed to compare perioperative indicators between patients with regular and huge HCC. RESULTS: The regular HCC group exhibited a shorter median operative duration than the huge HCC group. The IWATE criteria revealed higher scores in the huge HCC group than in the regular HCC group. No significant differences were observed between the two groups in Pringle time, drainage tube removal, duration of hospital stays, blood loss volume, blood product transfusion, margin status, conversion rate to open surgery, bile leakage, in-hospital mortality, and reoperation rate. CONCLUSION: Robotic liver resection is feasible for huge HCC, with effective perioperative risk management potentially improving outcomes for subsequent minimally invasive surgeries.

Enhanced NK cell activation via eEF2K-mediated potentiation of the cGAS-STING pathway in hepatocellular carcinoma.

BACKGROUND: Liver cancer, particularly hepatocellular carcinoma (HCC), is characterized by a high mortality rate, attributed primarily to the establishment of an immunosuppressive microenvironment. Within this context, we aimed to elucidate the pivotal role of eukaryotic elongation factor 2 kinase (eEF2K) in orchestrating the infiltration and activation of natural killer (NK) cells within the HCC tumor microenvironment. By shedding light on the immunomodulatory mechanisms at play, our findings should clarify HCC pathogenesis and help identify potential therapeutic intervention venues. METHODS: We performed a comprehensive bioinformatics analysis to determine the functions of eEF2K in the context of HCC. We initially used paired tumor and adjacent normal tissue samples from patients with HCC to measure eEF2K expression and its correlation with prognosis. Subsequently, we enrolled a cohort of patients with HCC undergoing immunotherapy to examine the ability of eEF2K to predict treatment efficacy. To delve deeper into the mechanistic aspects, we established an eEF2K-knockout cell line using CRISPR/Cas9 gene editing. This step was crucial for verifying activation of the cGAS-STING pathway and the subsequent secretion of cytokines. To further elucidate the role of eEF2K in NK cell function, we applied siRNA-based techniques to effectively suppress eEF2K expression in vitro. For in vivo validation, we developed a tumor-bearing mouse model that enabled us to compare the infiltration and activation of NK cells within the tumor microenvironment following various treatment strategies. RESULTS: We detected elevated eEF2K expression within HCC tissues, and this was correlated with an unfavorable prognosis (30.84 vs. 20.99 months, P = 0.033). In addition, co-culturing eEF2K-knockout HepG2 cells with dendritic cells led to activation of the cGAS-STING pathway and a subsequent increase in the secretion of IL-2 and CXCL9. Moreover, inhibiting eEF2K resulted in notable NK cell proliferation along with apoptosis reduction. Remarkably, after combining NH125 and PD-1 treatments, we found a significant increase in NK cell infiltration within HCC tumors in our murine model. Our flow cytometry analysis revealed reduced NKG2A expression and elevated NKG2D expression and secretion of granzyme B, TNF-α, and IFN-γ in NK cells. Immunohistochemical examination confirmed no evidence of damage to vital organs in the mice treated with the combination therapy. Additionally, we noted higher levels of glutathione peroxidase and lipid peroxidation in the peripheral blood serum of the treated mice. CONCLUSION: Targeted eEF2K blockade may result in cGAS-STING pathway activation, leading to enhanced infiltration and activity of NK cells within HCC tumors. The synergistic effect achieved by combining an eEF2K inhibitor with PD-1 antibody therapy represents a novel and promising approach for the treatment of HCC.

Prevalence, patterns, risk factors and outcomes of peritoneal metastases after laparoscopic hepatectomy for hepatocellular carcinoma: a multicenter study from China.

Background: We aim to investigate the prevalence, patterns, risk factors, and outcomes of peritoneal metastases (PM) after curative laparoscopic hepatectomy (LH) for hepatocellular carcinoma (HCC). Methods: A multicenter cohort of 2,138 HCC patients who underwent curative LH from August 2010 to December 2016 from seven hospitals in China was retrospectively analyzed. The incidence of PM following LH was evaluated and compared with that in open hepatectomy (OH) after 1:1 propensity score matching (PSM). Results: PM prevalence was 5.1% (15/295) in the early period [2010-2013], 2.6% (47/1,843) in the later period [2014-2016], and 2.9% (62/2,138) in all LH patients, which was similar to 4.0% (59/1,490) in the OH patients. The recurrence patterns, timing, and treatment did not significantly vary between the LH and OH patients (P>0.05). Multivariate logistic regression revealed that tumor diameter >5 cm, non-anatomical resection, presence of microvascular invasion, and lesions <2 cm from major blood vessels were independent risk factors of PM after LH. Of the 62 cases with PM, 26 (41.9%) had PM only, 34 (54.9%) had intrahepatic recurrence (IHR) and PM, and 2 (3.2%) had synchronous extraperitoneal metastases (EPM). Patients with resectable PM had a 5-year overall survival (OS) of 65.0% compared to 9.0% for unresectable PM (P=0.001). Conclusions: The prevalence, patterns and independent risk factors of PM were identified for HCC patients after LH. LH was not associated with increased incidence of PM in HCC patients for experienced surgeons. Surgical re-excision of PM was associated with prolonged survival.

Short-term and long-term outcomes after robotic versus open hepatectomy in patients with large hepatocellular carcinoma: a multicenter study.

BACKGROUND: Robotic hepatectomy (RH) is currently widely accepted and it is associated with some benefits when compared to open hepatectomy (OH). However, whether such benefits can still be achieved for patients with large hepatocellular carcinoma (HCC) remain unclear. This study aimed to evaluate the short-term and long-term outcomes of patients undergoing RH or OH. METHODS: Perioperative and survival data from patients with large HCC who underwent RH or OH between January 2010 and December 2020 were collected from eight centres. Propensity score matching (PSM) was performed to minimise potential biases. RESULTS: Using predefined inclusion criteria, 797 patients who underwent OH and 309 patients who underwent RH were enroled in this study. After PSM, 280 patients in the robotic group had shorter operative time (median 181 vs. 201 min, P <0.001), lower estimated blood loss (median 200 vs. 400 ml, P <0.001), and shorter postoperative length of stay (median 6 vs. 9 days, P <0.001) than 465 patients in the open group. There were no significant differences between the two groups in overall survival and recurrence-free survival. Cox analysis showed AFP greater than 400 ng/ml, tumour size greater than 10 cm, and microvascular invasion were independent risk factors for overall survival and recurrence-free survival. After PSM, subgroup analysis showed that patients with a huge HCC (diameter >10 cm) who underwent RH had significantly lower estimated blood loss (median 200.0 vs. 500.0 min, P <0.001), and shorter length of stay (median 7 vs. 10 days, P <0.001) than those who underwent OH. CONCLUSION: Safety and feasibility of RH and OH for patients with large HCC were comparable. RH resulted in similar long-term survival outcomes as OH.

Lenvatinib plus anti-PD-1 antibodies as conversion therapy for patients with unresectable intermediate-advanced hepatocellular carcinoma: a single-arm, phase II trial.

BACKGROUND: Over 70% of the patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage and lose the opportunity for radical surgery. Combination therapy of tyrosine kinase inhibitors (TKIs) and anti-programmed cell death protein-1 (PD-1) antibodies has achieved a high tumor response rate in both the first-line and second-line treatment of advanced HCC. However, few studies have prospectively evaluated whether TKIs plus anti-PD-1 antibodies could convert unresectable intermediate-advanced HCC into resectable disease. METHODS: This single-arm, phase II study enrolled systemic therapy-naïve adult patients with unresectable Barcelona Clinic Liver Cancer stage B or C HCC. Patients received oral lenvatinib one time per day plus intravenous anti-PD-1 agents every 3 weeks (one cycle). Tumor response and resectability were evaluated before the fourth cycle, then every two cycles. The primary endpoint was conversion success rate by investigator assessment. Secondary endpoints included objective response rate (ORR) by independent imaging review (IIR) assessment per modified RECIST (mRECIST) and Response Evaluation Criteria in Solid Tumors, V.1.1 (RECIST 1.1), progression-free survival (PFS) and 12-month recurrence-free survival (RFS) rate by IIR per mRECIST, R0 resection rate, overall survival (OS), and safety. Biomarkers were assessed as exploratory objectives. RESULTS: Of the 56 eligible patients enrolled, 53 (94.6%) had macrovascular invasion, and 16 (28.6%) had extrahepatic metastasis. The median follow-up was 23.5 months. The primary endpoint showed a conversion success rate of 55.4% (31/56). ORR was 53.6% per mRECIST and 44.6% per RECIST 1.1. Median PFS was 8.9 months, and median OS was 23.9 months. Among the 31 successful conversion patients, 21 underwent surgery with an R0 resection rate of 85.7%, a pathological complete response rate of 38.1%, and a 12-month RFS rate of 47.6%. Grade ≥3 treatment-related adverse events were observed in 42.9% of patients. Tumor immune microenvironment analysis of pretreatment samples displayed significant enrichment of CD8+ T cells (p=0.03) in responders versus non-responders. CONCLUSION: Lenvatinib plus anti-PD-1 antibodies demonstrate promising efficacy and tolerable safety as conversion therapy in unresectable HCC. Pre-existing CD8+ cells are identified as a promising biomarker for response to this regimen. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry, ChiCTR1900023914.

International experts consensus guidelines on robotic liver resection in 2023.

The robotic liver resection (RLR) has been increasingly applied in recent years and its benefits shown in some aspects owing to the technical advancement of robotic surgical system, however, controversies still exist. Based on the foundation of the previous consensus statement, this new consensus document aimed to update clinical recommendations and provide guidance to improve the outcomes of RLR clinical practice. The guideline steering group and guideline expert group were formed by 29 international experts of liver surgery and evidence-based medicine (EBM). Relevant literature was reviewed and analyzed by the evidence evaluation group. According to the WHO Handbook for Guideline Development, the Guidance Principles of Development and Amendment of the Guidelines for Clinical Diagnosis and Treatment in China 2022, a total of 14 recommendations were generated. Among them were 8 recommendations formulated by the GRADE method, and the remaining 6 recommendations were formulated based on literature review and experts' opinion due to insufficient EBM results. This international experts consensus guideline offered guidance for the safe and effective clinical practice and the research direction of RLR in future.

Robotic versus laparoscopic surgery for sporadic benign insulinoma: Short- and long-term outcomes.

BACKGROUND: Minimally invasive surgery is the optimal treatment for insulinoma. The present study aimed to compare short- and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma. METHODS: A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted. The demographic, perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups. RESULTS: A total of 85 patients were enrolled, including 36 with laparoscopic approach and 49 with robotic approach. Enucleation was the preferred surgical procedure. Fifty-nine patients (69.4%) underwent enucleation; among them, 26 and 33 patients underwent laparoscopic and robotic surgery, respectively. Robotic enucleation had a lower conversion rate to laparotomy (0 vs. 19.2%, P = 0.013), shorter operative time (102.0 vs. 145.5 min, P = 0.008) and shorter postoperative hospital stay (6.0 vs. 8.5 d, P = 0.002) than laparoscopic enucleation. There were no differences between the groups in terms of intraoperative blood loss, the rates of postoperative pancreatic fistula and complications. After a median follow-up of 65 months, two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence. CONCLUSIONS: Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time, which might lead to a reduction in postoperative hospital stay.

Short-term outcomes of robotic versus open hepatectomy among overweight patients with hepatocellular carcinoma: a propensity score-matched study.

BACKGROUND: Robotic hepatectomy (RH) has gradually been accepted as it has overcome some of the limitations of open hepatectomy (OH). This study was to compare short-term outcomes in RH and OH for overweight (preoperative body mass index ≥ 25 kg/m²) patients with hepatocellular carcinoma (HCC). METHODS: Perioperative and postoperative data from these patients who underwent RH or OH between January 2010 and December 2020 were retrospectively analyzed. Propensity score matching (PSM) analysis was performed to determine the impact of RH versus OH on the prognosis of overweight HCC patients. RESULTS: All 304 overweight HCC patients were included, 172 who were underwent RH, and 132 who were underwent OH. After the 1:1 PSM, there were 104 patients in both RH and OH groups. After PSM, the RH group of patients had a shorter operative time, less estimated blood loss (EBL), a longer total clamping time, a shorter postoperative length of stay (LOS), less chance of surgical site infection and less rates of blood transfusion (all P < 0.05) compared to the OH patients. The differences between operative time, EBL and LOS were more significant in obese patients. RH was found to be an independent protective factor of EBL ≥ 400ml relative to OH in overweight patients for the first time. CONCLUSIONS: RH was safe and feasible in overweight HCC patients. Compared with OH, RH has advantages in terms of operative time, EBL, postoperative LOS, and surgical site infection. Carefully selected overweight patients should be considered for RH.

Multilevel effective surgical workflow recognition in robotic left lateral sectionectomy with deep learning: experimental research.

BACKGROUND: Automated surgical workflow recognition is the foundation for computational models of medical knowledge to interpret surgical procedures. The fine-grained segmentation of the surgical process and the improvement of the accuracy of surgical workflow recognition facilitate the realization of autonomous robotic surgery. This study aimed to construct a multigranularity temporal annotation dataset of the standardized robotic left lateral sectionectomy (RLLS) and develop a deep learning-based automated model for multilevel overall and effective surgical workflow recognition. METHODS: From December 2016 to May 2019, 45 cases of RLLS videos were enrolled in our dataset. All frames of RLLS videos in this study are labeled with temporal annotations. The authors defined those activities that truly contribute to the surgery as effective frames, while other activities are labeled as under-effective frames. Effective frames of all RLLS videos are annotated with three hierarchical levels of 4 steps, 12 tasks, and 26 activities. A hybrid deep learning model were used for surgical workflow recognition of steps, tasks, activities, and under-effective frames. Moreover, the authors also carried out multilevel effective surgical workflow recognition after removing under-effective frames. RESULTS: The dataset comprises 4 383 516 annotated RLLS video frames with multilevel annotation, of which 2 418 468 frames are effective. The overall accuracies of automated recognition for Steps, Tasks, Activities, and under-effective frames are 0.82, 0.80, 0.79, and 0.85, respectively, with corresponding precision values of 0.81, 0.76, 0.60, and 0.85. In multilevel effective surgical workflow recognition, the overall accuracies were increased to 0.96, 0.88, and 0.82 for Steps, Tasks, and Activities, respectively, while the precision values were increased to 0.95, 0.80, and 0.68. CONCLUSION: In this study, the authors created a dataset of 45 RLLS cases with multilevel annotations and developed a hybrid deep learning model for surgical workflow recognition. The authors demonstrated a fairly higher accuracy in multilevel effective surgical workflow recognition when under-effective frames were removed. Our research could be helpful in the development of autonomous robotic surgery.

Comparison of survival benefit between salvage surgery after conversion therapy versus surgery alone for hepatocellular carcinoma with portal vein tumor thrombosis: a propensity score analysis.

BACKGROUND: Salvage surgery after conversion therapy with a combination of tyrosine kinase inhibitor and anti-programmed death-1 antibody has shown improved survival benefits in patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). We aimed to compare the survival benefits in a retrospective cohort of patients with HCC with PVTT who underwent salvage surgery after conversion therapy and surgery alone. METHODS: From January 2015 to October 2021, we selected patients diagnosed with HCC with PVTT who underwent liver resection at Chinese PLA General Hospital. The primary endpoint in the comparison of survival benefits between conversion therapy and surgery-alone groups was recurrence-free survival. Propensity score matching was applied to reduce any potential bias in the study. RESULTS: The 6-, 12-, and 24-month recurrence-free survival rates in the conversion and surgery alone groups were 80.3% vs 36.5%, 65.4% vs 29.4%, and 56% vs 21%, respectively. On multivariable Cox regression analyses, conversion therapy significantly reduced HCC-related mortality and HCC recurrence rates compared with surgery alone. CONCLUSIONS: For patients with HCC with PVTT, surgery after conversion therapy is in relationship with increased survival in comparison with surgery alone.

Early and late recurrence patterns of pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: a multicenter study.

BACKGROUND: Survival after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) remains poor because of high incidences of recurrence. The risk factors, patterns, and long-term prognosis in patients with early recurrence and late recurrence (ER and LR) for PDAC after PD were studied. METHODS: Data from patients who underwent PD for PDAC were analyzed. Recurrence was divided into ER (ER ≤1 years) and LR (LR >1 years) using the time to recurrence after surgery. Characteristics and patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with ER and LR. RESULTS: Among the 634 patients, 281 (44.3%) and 249 (39.3%) patients developed ER and LR, respectively. In the multivariate analysis, preoperative CA19-9 levels, resection margin status, and tumor differentiation were significantly associated with both ER and LR, while lymph node metastasis and perineal invasion were associated with LR. Patients with ER, when compared with patients with LR, showed a significantly higher proportion of liver-only recurrence ( P <0.05), and worse median PRS (5.2 vs. 9.3 months, P <0.001). Lung-only recurrence had a significantly longer PRS when compared with liver-only recurrence ( P <0.001). Multivariate analysis demonstrated that ER and irregular postoperative recurrence surveillance were independently associated with a worse prognosis ( P <0.001). CONCLUSION: The risk factors for ER and LR after PD are different for PDAC patients. Patients who developed ER had worse PRS than those who developed LR. Patients with lung-only recurrence had a significantly better prognosis than those with other recurrent sites.

Significance of anatomical resection and resection margin status in patients with HBV-related hepatocellular carcinoma and microvascular invasion: a multicenter propensity score-matched study.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for patients with hepatocellular carcinoma (HCC) after hepatectomy. This study aimed to evaluate the impact of anatomical resection (AR) versus nonanatomical resection (NAR) combined with resection margin (RM) (narrow RM <1 cm vs. wide RM ≥1 cm) on long-term prognosis in hepatitis B virus-related HCC patients with MVI. MATERIALS AND METHODS: Data from multicenters on HCC patients with MVI who underwent hepatectomy was analyzed retrospectively. Propensity score matching analysis was performed in these patients. RESULTS: The 1965 enrolled patients were divided into four groups: AR with wide RM ( n =715), AR with narrow RM ( n =387), NAR with wide RM ( n =568), and NAR with narrow RM ( n =295). Narrow RM ( P <0.001) and NAR ( P <0.001) were independent risk factors for both overall survival and recurrence-free survival in these patients based on multivariate analyses. For patients in both the AR and NAR groups, wide RM resulted in significantly lower operative margin recurrence rates than those patients in the narrow RM groups after propensity score matching ( P =0.002 and 0.001). Patients in the AR with wide RM group had significantly the best median overall survival (78.9 vs. 51.5 vs. 48.0 vs. 36.7 months, P <0.001) and recurrence-free survival (23.6 vs. 14.8 vs. 17.8 vs. 9.0 months, P <0.001) than those in the AR with narrow RM, NAR with wide RM or with narrow RM groups, respectively. CONCLUSIONS: If technically feasible and safe, AR combined with wide RM should be the recommended therapeutic strategy for HCC patients who are estimated preoperatively with a high risk of MVI.

Derivation and validation of a preoperative prognostic model for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) remains poor even after radical pancreaticoduodenectomy (PD). The study aimed to develop and validate a novel preoperative prognostic model to accurately predict the long-term survival of patients with PDAC. METHODS: Patients with PDAC of pancreatic head from Chinese PLA General Hospital were included. The preoperative PDAC model with contour plots was developed using a non-linear model in the training cohort and then tested in the validation cohort. RESULTS: Of 421 patients who met the inclusion criteria, 280 were in the training cohort and 141 in the validation cohort. Contour plots for preoperative PDAC model were established to visually predict the survival probabilities of these patients, based on preoperative carbohydrate antigen 19-9, preoperative fibrinogen to albumin ratio and pain symptoms. This model stratified patients into low- and high-risk groups with distinctly different long-term survival in the training cohort [median overall survival (OS) 32.1 vs. 17.5 months; median recurrence-free survival (RFS) 19.3 vs. 10.0 months, both P < 0.001] and the validation cohort (median OS 28.3 vs. 19.0 months; median RFS 17.5 vs. 11.2 months, both P < 0.001). Time-dependent receiver operating characteristic and decision curve analyses revealed that the model provided higher diagnostic accuracy and superior net benefit compared to other staging systems. CONCLUSIONS: This study constructed and validated a novel preoperative prognostic model that can accurately and conveniently predict the long-term survival of patients with resectable PDAC of pancreatic head. Besides, the model can screen high-risk patients with poor prognosis, which may provide references for personal treatment strategies in the future.

Robotic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: Analysis of surgical outcomes and long-term prognosis in a high-volume center.

BACKGROUND: Robotic pancreaticoduodenectomy (RPD) has been reported to be safe and feasible for patients with pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head. This study aimed to analyze the surgical outcomes and risk factors for poor long-term prognosis of these patients. METHODS: Data from patients who underwent RPD for PDAC of pancreatic head were retrospectively analyzed. Multivariate Cox regression analysis was used to seek the independent prognostic factors for overall survival (OS), and an online nomogram calculator was developed based on the independent prognostic factors. RESULTS: Of the 273 patients who met the inclusion criteria, the median operative time was 280.0 minutes, the estimated blood loss was 100.0 mL, the median OS was 23.6 months, and the median recurrence-free survival (RFS) was 14.4 months. Multivariate analysis showed that preoperative carbohydrate antigen 19-9 (CA19-9) [hazard ratio (HR) = 2.607, 95% confidence interval (CI): 1.560-4.354, P < 0.001], lymph node metastasis (HR = 1.429, 95% CI: 1.005-2.034, P = 0.047), tumor moderately (HR = 3.190, 95% CI: 1.813-5.614, P < 0.001) or poorly differentiated (HR = 5.114, 95% CI: 2.839-9.212, P < 0.001), and Clavien-Dindo grade ≥ III (HR = 1.657, 95% CI: 1.079-2.546, P = 0.021) were independent prognostic factors for OS. The concordance index (C-index) of the nomogram constructed based on the above four independent prognostic factors was 0.685 (95% CI: 0.640-0.729), which was significantly higher than that of the AJCC staging (8th edition): 0.541 (95% CI: 0.493-0.589) (P < 0.001). CONCLUSIONS: This large-scale study indicated that RPD was feasible for PDAC of pancreatic head. Preoperative CA19-9, lymph node metastasis, tumor poorly differentiated, and Clavien-Dindo grade ≥ III were independent prognostic factors for OS. The online nomogram calculator could predict the OS of these patients in a simple and convenient manner.

A novel online calculator to predict early recurrence and long-term survival of patients with resectable pancreatic ductal adenocarcinoma after pancreaticoduodenectomy: A multicenter study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is prone to relapse even after radical pancreaticoduodenectomy (PD) (including robotic, laparoscopic and open approach). This study aimed to develop an online nomogram calculator to predict early recurrence (ER) (within one year after surgery) and long-term survival in patients with PDAC. METHODS: Patients with PDAC after radical PD were included. Univariate and multivariate logistic regression analysis was used to identify independent risk factors. An online nomogram calculator was developed based on independent risk factors in the training cohort and then tested in the internal and external validation cohorts. RESULTS: Of the 569 patients who met the inclusion criteria, 310, 155, and 104 patients were in the training, internal and external validation cohorts, respectively. Multivariate analysis revealed that preoperative carbohydrate antigen19-9 (CA19-9) [Odds Ratio (OR) 1.002; 95% confidence interval (CI) 1.001-1.003; P = 0.001], fibrinogen/albumin (FAR) (OR 1.132; 95% CI 1.012-1.266; P = 0.029), N stage (OR 2.291; 95% CI 1.283-4.092; P = 0.005), and tumor differentiation (OR 3.321; 95% CI 1.278-8.631; P = 0.014) were independent risk factors for ER. Nomogram based on the above four factors achieved good C-statistics of 0.772, 0.767 and 0.765 in predicting ER in the training, internal and external validation cohorts, respectively. Time-dependent ROC analysis (timeROC) and decision curve analysis (DCA) revealed that the nomogram provided superior diagnostic capacity and net benefit compared with other staging systems. CONCLUSION: This multi-center study developed and validated an online nomogram calculator that can predict ER and long-term survival in patients with PDAC with high degrees of stability and accuracy.

The HBV Specially-Related Long Noncoding RNA HBV-SRL Involved in the Pathogenesis of Hepatocellular Carcinoma.

Hepatitis B virus (HBV) is one of the major risk factors for HCC (hepatocellular carcinoma) occurrence with a diverse role in the pathogenesis of HCC. More works need to be performed to elucidate a more thorough understanding of the molecular mechanisms involving in HBV-induced HCC, although some mechanisms such as genome integration have been reported. In the present study, aberrantly expressed lncRNAs were identified between HCC tumor tissues with or without HBV infection. Among these molecules, HBV specially-related long noncoding RNA (HBV-SRL) was further found to correlate with poor prognosis and a shorter overall survival time in HCC patients with HBV infection. Additionally, HBV-SRL was found function as oncogene by upregulating the NF-κB2 expression. These data suggest that HBV infection altered gene expression pattern in liver cells which contributed to HBV-related HCC development, and HBV-SRL may serve as a new molecular marker or potential therapeutic target of HBV-related HCC.

Short- and long-term outcomes after robotic and open liver resection for elderly patients with hepatocellular carcinoma: a propensity score-matched study.

BACKGROUND: Robotic liver resection (RLR) has increasingly been accepted as it has overcome some of the limitations of open liver resection (OLR), while the outcomes following RLR in elderly patients with hepatocellular carcinoma (HCC) are still uncertain. This study aimed to evaluate the short and long-term outcomes of RLR vs. OLR in elderly HCC patients. METHODS: Perioperative data of elderly patients (≥ 65 years) with HCC who underwent RLR or OLR between January 2010 and December 2020 were retrospectively analyzed. A 1:2 propensity score-matched (PSM) analysis was performed to minimize the differences between RLR and OLR groups. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: Of the 427 elderly HCC patients included in this study, 113 underwent RLR and 314 underwent OLR. After the 1:2 PSM, there were 100 and 178 patients in the RLR and the OLR groups, respectively. The RLR group had a less estimated blood loss (EBL), a shorter postoperative length of stay (LOS), and a lower complications rate (all P < 0.05), compared with the OLR group before and after PSM. Univariable and multivariable analyses showed that advanced age and surgical approaches were not independent risk factors for long-term prognosis. The two groups of elderly patients who were performed RLR or OLR had similar OS (median OS 52.8 vs. 57.6 months) and RFS (median RFS 20.4 vs. 24.6 months) rates after PSM. CONCLUSIONS: RLR was comparable to OLR in feasibility and safety. For elderly patients with HCC, RLR resulted in similar oncologic and survival outcomes as OLR.

Robotic versus open pancreaticoduodenectomy for distal cholangiocarcinoma: a multicenter propensity score-matched study.

BACKGROUND: Pancreatoduodenectomy is the only potentially curative treatment for distal cholangiocarcinoma (DCC). In this study, we sought to compare the perioperative and oncological outcomes of robotic pancreaticoduodenectomy (RPD) and open pancreaticoduodenectomy (OPD) based on a multicenter propensity score-matched study. METHODS: Consecutive patients with DCC who underwent RPD or OPD from five centers in China between January 2014 and June 2019 were included. A 1:1 propensity score matching (PSM) was performed. Univariable and multivariable Cox regression analyses were used to identify independent prognosis factors for overall survival (OS) and recurrence-free survival (RFS) of these patients. RESULTS: A total of 217 patients and 228 patients underwent RPD and OPD, respectively. After PSM, 180 patients in each group were enrolled. There were no significant differences in operative time, lymph node harvest, intraoperative transfusion, vascular resection, R0 resection, postoperative major morbidity, reoperation, 90-day mortality, and long-term survival between the two groups before and after PSM. Whereas, compared with the OPD group, the RPD group had significantly lower estimated blood loss (150.0 ml vs. 250.0 ml; P < 0.001), and a shorter postoperative length of stay (LOS) (12.0 days vs. 15.0 days; P < 0.001). Multivariable analysis showed carbohydrate antigen 19-9 (CA19-9), R0 resection, N stage, perineural invasion, and tumor differentiation significantly associated with OS and RFS of these patients. CONCLUSIONS: RPD was comparable to OPD in feasibility and safety. For patients with DCC, RPD resulted in similar oncologic and survival outcomes as OPD.

Reducing Postoperative Recurrence of Early-Stage Hepatocellular Carcinoma by a Wound-Targeted Nanodrug.

New strategies to decrease risk of relapse after surgery are needed for improving 5-year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound-targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti-PD-L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface-coated with platelet membrane (PM) to achieve surgical site targeting in a self-amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti-PD-L1 antibody on the PM surface. The resulting nano-formulation, abbreviated as a-PM-S-MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a-PM-S-MSNP generate potent anti-HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti-HCC immunity and anti-angiogenesis effect at tumor sites. More importantly, microscopic inspection of a-PM-S-MSNP treated mice shows that 2 out 6 are histologically tumor-free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a-PM-S-MSNP can efficiently inhibit post-surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus is the key to robot-assisted thrombectomy for Mayo III/IV tumor thrombus.

BACKGROUND: The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. METHOD: A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. RESULTS: All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. CONCLUSIONS: The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.