Outcomes of Salvage Surgery for Initially Unresectable Hepatocellular Carcinoma Converted by Transcatheter Arterial Chemoembolization Combined with Lenvatinib plus Anti-PD-1 Antibodies: A Multicenter Retrospective Study.

Introduction: The actual rate of conversion surgery and its prognostic advantages remain unclear. This study aimed to assess the outcomes of salvage surgery after conversion therapy with triple therapy (transcatheter arterial chemoembolization [TACE] combined with lenvatinib plus anti-PD-1 antibodies) in patients with initially unresectable hepatocellular carcinoma (uHCC). Methods: Patients with initially uHCC who received at least one cycle of first-line triple therapy and salvage surgery at five major cancer centers in China were included. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS) rates after salvage surgery. The secondary endpoints were perioperative complications, 90-day mortality, and pathological tumor response. Results: Between June 2018 and December 2021, 70 patients diagnosed with uHCC who underwent triple therapy and salvage surgery were analyzed: 39 with Barcelona Clinic Liver Cancer (BCLC) stage C, 22 with BCLC stage B, and 9 with BCLC stage A disease. The median interval between the start of triple therapy and salvage surgery was 4.3 months (range, 1.7-14.2 months). Pathological complete response and major pathological response were observed in 29 (41.4%) and 59 (84.3%) patients, respectively. There were 2 cases of perioperative mortality (4.3%) and 5 cases of severe perioperative complications (7.1%). With a median follow-up of 12.9 months after surgery (range, 0.3-36.8 months), the median OS and RFS were not reached. The 1- and 2-year OS rates were 97.1% and 94.4%, respectively, and the corresponding RFS rates were 68.9% and 54.4%, respectively. Conclusion: First-line combination of TACE, lenvatinib, and anti-PD-1 antibodies provides a better chance of conversion therapy in patients with initially uHCC. Furthermore, salvage surgery after conversion therapy is effective and safe and has the potential to provide excellent long-term survival benefits.

A novel Laennec's capsule tunnel approach for pure laparoscopic left hemihepatectomy: a propensity score matching study.

Background: With the development of laparoscopic hepatectomy, there are different surgical approaches and pedicle anatomical methods for laparoscopic left hepatectomy. Combined with our practical experience, we proposed a method of transhepatic Laennec membrane tunnel for laparoscopic left hemihepatectomy (LT-LLH) and investigated the feasibility by comparison with the extrahepatic Glissonian approach for laparoscopic left hemihepatectomy (GA-LLH). Patients and methods: The data of patients who underwent laparoscopic left hepatectomy in the Department of Hepatobiliary Pancreatic surgery of Fujian Provincial Hospital from December 2019 to March 2022 were analyzed retrospectively. Among them, 45 cases underwent laparoscopic left hemihepatectomy with an extrahepatic Glissonian approach, and 38 cases underwent laparoscopic left hemihepatectomy via transhepatic Laennec membrane tunnel approach. A 1:1 propensity score matching (PSM) method was performed to compare the perioperative indexes and long-term tumor prognosis between the two groups. Results: After 1:1 PSM, 33 patients in each group were selected for further analysis. Compared with the GA-LLH group, the operation time of the LT-LLH group was shorter. There was no significant difference in the incidence of total complications between the two groups. Moreover, no statistical differences were found in disease-free survival and overall survival between the two groups. Conclusion: It is safe, faster, and convenient for selective appropriate cases to carry out laparoscopic left hemihepatectomy through the hepatic Laennec membrane tunnel, which is suitable for clinical promotion.

Long-term outcomes of anatomic vs. non-anatomic resection in intrahepatic cholangiocarcinoma with hepatolithiasis: A multicenter retrospective study.

Background: The benefits of anatomic resection (AR) vs. non-anatomic resection (NAR) in patients with primary intrahepatic cholangiocarcinoma (ICC) with hepatolithiasis (HICC) are unclear. This study aimed to compare the long-term outcomes of AR vs. NAR in patients with HICC. Methods: A total of 147 consecutive patients with HICC who underwent R0 hepatectomy were included. Overall survival (OS) and recurrence-free survival (RFS) following AR vs. NARs were compared using a 1:1 propensity score matching (PSM) analysis. A subgroup analysis was also conducted according to whether there are lymph node metastases (LNM). Results: In a multivariate analysis, CA 19-9 (>39 U/L), microvascular invasion, LNM, and NAR were independent risk factors for poor RFS and OS rates, whereas multiple tumors were independent risk factors for OS. AR had better 1-, 3-, and 5-year RFS and OS rates than NAR (OS: 78.7, 58.9, and 28.5%, respectively, vs. 61.2, 25.4, and 8.8%, respectively; RFS: 59.5, 36.5, and 20.5%, respectively, vs. 38.2, 12.1, and 6.9%, respectively). After PSM, 100 patients were enrolled. The NAR group also had significantly poorer OS and RFS (OS: 0.016; RFS: p = 0.010) than the AR group. The subgroup analysis demonstrated that in HICC without LNM, OS and RFS were significantly poorer in the NAR group than the AR group, while no significant differences were observed in HICC with LNM before or after PSM. Conclusion: Anatomic resection was associated with better long-term survival outcomes than NAR in patients with HICC, except for patients with LNM.

miR-24-3p Regulates Epithelial-Mesenchymal Transition and the Malignant Phenotype of Pancreatic Adenocarcinoma by Regulating ASF1B Expression.

Anti-silencing function protein 1 homolog B (ASF1B) has been implicated in the occurrence and development of cancers. The present work explored the functional role and the expression regulation of ASF1B in pancreatic ductal adenocarcinoma (PDAC). Based on the real-time quantitative PCR (qRT-PCR) and immunohistochemistry (IHC), ASF1B was significantly upregulated in PDAC tissues. High expression of ASF1B was associated with a poor overall survival (OS) and recurrence-free survival (DFS) in the PDAC patients. ASF1B also showed a relatively higher expression in PDAC cells (AsPC-1, PANC-1) when compared with human pancreatic ductal epithelial cells (HPDFe-6). CCK8 and clone formation assay demonstrated that silencing ASF1B impaired the proliferation in PANC-1 and AsPC-1 cells, and Annexin V-PI staining showed an increased level of apoptosis upon ASF1B silencing. ASF1B silencing also suppressed the migration and invasion in PDAC cells, as revealed by Transwell assays. We further showed that miR-24-3p was downregulated in PDAC tissues and cells, which functionally interacted with ASF1B by dual-luciferase reporter assay. miR-24-3p negatively regulated ASF1B expression to modulate the malignant phenotype of PDAC cells. ASF1B shows high expression in PDAC, which promotes the malignancy and EMT process of PDAC cells. miR-24-3p is a negative regulator of ASF1B and is downregulated in PDAC cells. Our data suggest that targeting ASF1B/miR-24-3p axis may serve as an intervention strategy for the management of PDAC.

Textbook outcomes of hepatocellular carcinoma patients with sarcopenia: A multicenter analysis.

BACKGROUND: The impact of sarcopenia on textbook outcome (TO) after hepatectomy in hepatocellular carcinoma (HCC) patients remains unclear. This study aimed to investigate the association between sarcopenia and TO, to clarify its long and short-term prognostic value, and to develop a nomogram model based on sarcopenia and TO for survival prediction. METHODS: Patients who underwent HCC resection between January 2012 and March 2017 in three large hospitals in Fujian were retrospectively recruited and divided into sarcopenia and non-sarcopenia groups based on skeletal muscle index (SMI) values. TO was defined as no 30-day morality, no 30-day readmission, negative margins, no prolonged hospital stay, and no major complications. Multivariate regression was used to screen for clinical factors associated with TO. Nomograms of overall survival (OS) and recurrence-free survival (RFS) after hepatectomy for HCC were developed. RESULTS: A total of 1172 patients were included in the study. The TO rates were 28.74% (121/421 patients) in the sarcopenia group and 43.4% (326/751 patients) in the non-sarcopenia group. The results showed that sarcopenia was an independent predictor of TO (p < 0.001), TO was an independent predictor of perioperative treatment-related sarcopenia (PTRS)(p = 0.002), and TO was an independent predictor of OS and RFS (p < 0.001). Nomogram models based on sarcopenia and TO were generated and accurately predicted OS and RFS at 1, 3, and 5 years. CONCLUSION: Both sarcopenia and TO are independent predictors of OS and RFS after HCC resection. Sarcopenia was an independent predictor of TO. Sarcopenia influenced long-term survival by affecting short-term postoperative outcomes.

Optimization of a laparoscopic procedure for advanced intrahepatic cholangiocarcinoma based on the concept of "waiting time": a preliminary report.

INTRODUCTION: Clinicians increasingly perform laparoscopic surgery for intrahepatic cholangiocarcinoma (ICC). However, this surgery can be difficult in patients with advanced-stage ICC because of the complicated procedures and difficulty in achieving high-quality results. We compared the effects of a three-step optimized procedure with a traditional procedure for patients with advanced-stage ICC. METHODS: Forty-two patients with advanced-stage ICC who received optimized laparoscopic hemihepatectomy with lymph node dissection (LND, optimized group) and 84 propensity score-matched patients who received traditional laparoscopic hemihepatectomy plus LND (traditional group) were analyzed. Surgical quality, disease-free survival (DFS), and overall survival (OS) were compared. RESULTS: The optimized group had a lower surgical bleeding score (P = 0.038) and a higher surgeon satisfaction score (P = 0.001). Blood loss during hepatectomy was less in the optimized group (190 vs. 295 mL, P < 0.001). The optimized group had more harvested LNs (12.0 vs. 8.0, P < 0.001) and more positive LNs (8.0 vs. 5.0, P < 0.001), and a similar rate of adequate LND (88.1% vs. 77.4%, P = 0.149). The optimized group had longer median DFS (9.0 vs. 7.0 months, P = 0.018) and median OS (15.0 vs. 13.0 months, P = 0.046). In addition, the optimized group also had a shorter total operation time (P = 0.001), shorter liver resection time (P = 0.001), shorter LND time (P < 0.001), shorter hospital stay (P < 0.001), and lower incidence of total morbidities (14.3% vs. 36.9%, P = 0.009). CONCLUSIONS: Our optimization of a three-step laparoscopic procedure for advanced ICC was feasible, improved the quality of liver resection and LND, prolonged survival, and led to better intraoperative and postoperative outcomes.

Perioperative management of intrahepatic cholangiocarcinoma patients with hereditary coagulation factor V deficiency: a case report and literature review.

Background: Coagulation factor V (FV) is an essential factor to regulate and participate in the initial coagulation reaction, and it is the most important prothrombin activator in vivo. FV congenital deficiency is a rare hereditary disease, it exposes patients to hemorrhagic risk, with high morbi-mortality. Clinically, laparoscopic major hepatectomy has its own risk of intraoperative hemorrhage, and moreover, coupled with the lack of FV will increase the risk of bleeding even life-threatening. However, several studies have reported the cases of patients with FV deficiency undergoing surgery, there is no report of laparoscopic major hepatectomy in patients with FV deficiency so far. Case Description: Here, we reported one case with no abdominal pain, nausea, vomiting, fever and other discomfort who was diagnosed with intrahepatic cholangiocarcinoma (IHC) complicated with hereditary FV deficiency and then received laparoscopic left hemihepatectomy after conversion therapy. After preoperative sufficient infusion of fresh frozen plasma (FFP) to improve coagulation function, careful intraoperative operation, and strict postoperative monitoring, no obvious complications occurred in the perioperative period. At present, the patient has an overall survival time of 18 months and is still followed up. Conclusions: It is suggested that laparoscopic major hepatectomy is safe and feasible for patients with hereditary FV deficiency under careful perioperative management.

Lenvatinib combined with anti-PD-1 antibodies plus transcatheter arterial chemoembolization for neoadjuvant treatment of resectable hepatocellular carcinoma with high risk of recurrence: A multicenter retrospective study.

Background: Early recurrence is common after surgical resection (SR) for hepatocellular carcinoma (HCC) with high risk of recurrence and is associated with poor prognosis. The combinations of lenvatinib (LEN), anti-PD-1 antibodies (PD-1) and transcatheter arterial chemoembolization (TACE) (triple therapy) has shown better trend in tumor response and survival outcomes on unresectable HCC. It is unknown whether triple therapy for neoadjuvant treatment of resectable HCC with high risk of recurrence is effective. This article aimed to compare the outcomes of surgery alone and neoadjuvant combination treatment with triple therapy before SR in patients with HCC with high risk of recurrence. Methods: A retrospective study was conducted on patients diagnosed with HCC with high risk of recurrence who received treatment with or without triple therapy. The records of 24 patients in the triple therapy group and 76 patients in the surgery-alone group were analyzed. Propensity score matching (PSM) was performed to minimize the influence of potential confounders. Results: One hundred patients were enrolled. In the triple therapy group, 8 (33.3%) and 12 (50.0%) patients had complete and partial responses, respectively, as assessed by an investigator. Before PSM, the overall survival (OS) rates for the triple therapy group at 6, 12, 18, and 24 months were 100.0%, 100.0%, 100.0%, and 85.7%, respectively, compared with corresponding 92.1%, 73.7%, 53.9%, and 48.7% for the surgery-alone group (P<0.001). The disease-free survival (DFS) rates were 82.2%, 66.95%, 48.8%, and 48.8% for the triple therapy and 41.92%, 28.34%, 27.05%, and 22.99% for the surgery-alone group (P=0.003). After PSM, DFS and OS were significantly longer in the triple therapy group than in the surgery-alone group (DFS, p=0.019; OS, p=0.003). Conclusions: Neoadjuvant combination treatment before SR had a high rate of tumor response and provided significantly better postoperative survival outcomes than surgery alone in patients with HCC with high risk of recurrence.

Impact of sarcopenia on the surgical outcomes in patients with hepatolithiasis: A multicenter 10-year experience.

BACKGROUND: The impact of sarcopenia on the surgical outcomes of hepatectomy for hepatolithiasis has not been investigated. The present study elucidated the effect of sarcopenia on short-term outcomes after hemihepatectomy for hepatolithiasis and investigated the benefit of different surgical approaches to hepatectomy in patients with sarcopenia. METHODS: Patients who underwent hemihepatectomy for hepatolithiasis at Fujian Provincial Hospital and 5 other medical centers from 2010 to 2020 were enrolled. The sarcopenic obesity subgroup had sarcopenia coexisting with obesity, and the sarcopenic nonobesity subgroup had sarcopenia without obesity. We analyzed the postoperative outcomes of the sarcopenia group, sarcopenic obesity subgroup and sarcopenic nonobesity subgroup and the corresponding benefits of different surgical approaches. RESULTS: Patients with sarcopenia (n = 481) had worse surgical outcomes than nonsarcopenia, such as longer postoperative hospital duration of stay, longer time to oral intake, longer time to bowel movement, and longer time to off-bed activities. In postoperative short-term outcomes, we also found that sarcopenia had higher rates of major complications, bile leakage, and intensive care unit occupancy than the nonsarcopenic group. Subgroup analysis showed that sarcopenic obesity subgroup (n = 182) had the worst results in intraoperative outcomes and postoperative short-term outcomes. Multivariate analysis identified sarcopenic obesity as a significant risk factor for postoperative hospital duration of stay (hazard ratio = 2.994, P < .001). Furthermore, the sarcopenic obesity and sarcopenic nonobesity (n = 299) subgroups benefited from laparoscopic surgery compared with open surgery, including postoperative recovery and major complications (all P < .05). However, sarcopenic nonobesity subgroup had more significant benefits of laparoscopy than the sarcopenic obesity subgroup. The learning curve for laparoscopic hemihepatectomy for the sarcopenic obesity subgroup had a plateau, and the surgical outcomes of the sarcopenic obesity subgroup were closer to the sarcopenic nonobesity subgroup after the plateau. CONCLUSION: Sarcopenia is associated with more adverse events after hepatectomy and patients with sarcopenic obesity have a higher incidence of adverse events. Patients with sarcopenia could benefit from laparoscopy. Compared with the sarcopenic obesity patients, the sarcopenic nonobesity patients benefited more from laparoscopy. Although the sarcopenic obesity patients had more complications and slower postoperative recovery than the sarcopenic nonobesity patients, laparoscopic also could improve their short-term outcomes, but a longer learning curve was required.

Laparoscopic segment 4b+5 liver resection for stage T3 gallbladder cancer.

BACKGROUND: There is still controversy over whether to perform laparoscopic surgery for T3 stage gallbladder cancer. In addition, the necessity of segment 4b+5 liver resection for stage T3 gallbladder has not been reported. This article aims to explore the safety, effectiveness, and short-term prognosis of laparoscopic segment 4b+5 liver resection for T3 stage gallbladder cancer. METHODS: This is a retrospective multicenter propensity score-matched study. Disease-free survival, perioperative complications, and intraoperative safety were analyzed to evaluate safety and effectiveness. RESULTS: There was no significant difference in the incidence of intraoperative bleeding, number of lymph nodes obtained, postoperative complications, or disease-free survival (DFS) between the open group (OG) and laparoscopic group (LG) (P > 0.05). The DFS time of the S4b+5 resection group (S4b5) was longer than that of the wedge group (P = 0.016). Cox regression showed that positive margins (HR, 5.32; 95% CI 1.03-27.63; P = 0.047), lymph node metastasis (HR, 2.70; 95% CI 1.31-5.53; P = 0.007), and liver S4b+5 resection (HR, 0.30; 95% CI 0.14-0.66; P = 0.003) were independent risk factors for DFS. The operative time of indocyanine green (ICG) fluorescence-guided liver S4b5 segment resection was shorter than that of traditional laparoscopic S4b+5 resection guided by hepatic veins (P ≤ 0.001). CONCLUSION: Laparoscopic liver S4b+5 resection for T3 stage gallbladder cancer is safe and feasible and can prolong DFS. ICG fluorescence-guided negative staining may reduce the difficulty of the operation.

Multiple endocrine neoplasia type 1 involving both the liver and lung: a case report.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant tumor syndrome with a high degree of heterogeneity in clinical phenotypes, generally involving the parathyroid, anterior pituitary, and enteropancreas. In recent years, several new insights into the clinical features of MEN1 have been reported in the literature. However, it is not clear whether MEN1-associated primary tumors can occur in the liver. CASE PRESENTATION: We report the case of a 52-year-old man with multiple endocrine neoplasia type 1 diagnosed by genetic sequencing. After uniportal thoracoscopic right middle lobectomy, laparoscopic radical resection of the liver tumors, and radiofrequency ablation of the parathyroid space, the parathyroid hormone level decreased from 177 pg/ml to a normal level (20 pg/ml). No local tumor recurrence was observed during a follow-up of 5 months. CONCLUSION: We report the first case of MEN1 with simultaneous liver and lung involvement in which the patient underwent radical resection of the tumors, and we propose the possibility that the liver and other nonendocrine organs may also develop diseases associated with MEN1; although, this view needs further verification. Gene detection has crucial clinical significance for guiding diagnosis and treatment.

Integration of IgG and IgA autoantibodies for early diagnosis of hepatocellular carcinoma.

BACKGROUND: Autoantibodes against tumor-associated antigens (TAAs) have been recommended for the early diagnosis of malignancies. In this study, we intend to comprehensively evaluate the performances of four autoantibodies including anti-p53, CTAG1A, TIF1γ-IgG and anti-TIF1γ-IgA for the early diagnosis of hepatocellular carcinoma (HCC), and then determine an optimal panel of autoantibodies for early HCC diagnosis. METHODS: The performances of four autoantibodies were evaluated by enzyme-linked immunosorbent assay (ELISA) for the early diagnosis of HCC with 380 retrospective serum samples. A training set comprised of 92 patients with early HCC, 72 patients with hepatic benign lesions (HBL), and 86 healthy controls (HC) was used to develop the predictive model for early HCC. And then, data obtained from an independent validation set was applied to evaluate and validate the predictive model to distinguish the early HCC from the controls (HBL + HC). RESULTS: The results of the training set showed the levels and positive rates of four autoantibodies in early HCC group were significantly higher than that in HBL group/HC group (P < 0.01), of which anti-p53-IgG exhibited the highest AUC of 0.679, with 33.7% sensitivity at 93.7% specificity; the panel comprised of four autoantibodies showed the highest AUC for the patients with early HCC, up to 0.814 (95%CI 0.760-0.860), with 72.8% sensitivity at 84.2% specificity among all possible combinations of four autoantibodies. Additionally, this four-autoantibody panel showed the AUC of 0.824, 70.8% sensitivity at 84.2% specificity in the validation set. CONCLUSIONS: Serum IgG autoantibodies against p53, CTAG1A and TIF1γ, and IgA autoantibody against TIF1γ present the diagnostic value for early HCC, of which anti-p53-IgG is a preferable biomarker. The panel comprised of four autoantibodies might contribute to early HCC diagnosis.

Lenvatinib Combined with Anti-PD-1 Antibodies Plus Transcatheter Arterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Multicenter Retrospective Study.

BACKGROUND: Lenvatinib (LEN) combined with anti-PD-1 antibodies (PD-1) exerted promising effects on unresectable hepatocellular carcinoma (uHCC). We assessed the safety and clinical efficacy of triple therapy [LEN+PD-1+transcatheter arterial chemoembolization (TACE)] in uHCC. METHODS: uHCC patients with an ECOG PS score of 0-1 and Child-Pugh class A who underwent triple therapy were included. The primary endpoint was objective response rate (ORR) based on mRECIST. Secondary endpoints were conversion rate to liver resection and treatment-related adverse events. RESULTS: Between November 2018 and December 2020, 62 uHCC patients who underwent triple therapy at four major cancer centers in China were analyzed, including 35 in BCLC-C, 21 in BCLC-B, and 6 in BCLC-A. With a median follow-up of 12.2 months (range, 7.6-33.3 months), the investigator and blinded independent central review-assessed ORR were 80.6% and 77.4%, respectively. A total of 33 patients (53.2%) reached the standard of conversion to resectable HCC and 29 patients underwent resection. The median interval between start of triple therapy and resection was 123 days (range, 55-372 days). Pathological complete response and major pathological response were observed in 16 and 24 patients, respectively. Median overall survival and progression-free survival were not reached. Treatment-related adverse events occurred in 74.2% of the patients (grade ≥3, 14.5%; grade ≥4, 4.8%). CONCLUSION: Combination of LEN, PD-1 and TACE showed a high rate of tumor response and convert resection in uHCC patients, with manageable toxicity.

Inhibition of ceramide de novo synthesis ameliorates meibomian gland dysfunction induced by SCD1 deficiency.

High expression of stearoyl-CoA desaturase-1 (SCD1) in meibomian glands produces monounsaturated fatty acids that allow the biosynthesis of glycerolipids and other wax-esters but only the low production of sphingolipids. Here, we found that SCD1 deficiency in mice induces the spill of free fatty acids into a parallel pathway for ceramide biosynthesis, resulting in severe meibomian gland dysfunction associated with meibum accumulation in duct lumen and orifices and subsequent atrophy and loss of acinar cells. Genetic and pharmacological inhibition of SCD1 in mice resulted in meibomian gland pathological phenotypes, including local lipid microenvironment alterations, reduced normal cellular differentiation, increased keratinization, inflammatory cell infiltration, cell apoptosis, and mitochondrial dysfunction. However, inhibition of serine palmitoyltransferase, the initial enzyme in ceramide biosynthesis, improved meibomian gland metabolism and morphology in SCD1-deficient mice, resulting in normal cell differentiation and reduced inflammation infiltration, cell apoptosis, and keratinization. These results indicate that elevated levels of endogenous ceramides are a sign of MGD and suggest that inhibition of ceramide de novo biosynthesis could be a new clinical approach to treating MGD.

Prognostic value and association of sarcopenic obesity and systemic inflammatory indexes in patients with hepatocellular carcinoma following hepatectomy and the establishment of novel predictive nomograms.

BACKGROUND: The specific impacts of sarcopenic obesity (SO) on hepatocellular carcinoma (HCC) and the association between SO and systemic inflammation remain unclear. This study aimed to investigate the prognostic value and association of SO and systemic inflammation with outcomes after hepatectomy for HCC and develop novel nomograms based on SO and inflammatory indexes for survival prediction. METHODS: We retrospectively enrolled 452 patients with HCC who underwent radical hepatectomy between January 2012 and March 2015 in Fujian Provincial Hospital as the training cohort. In addition, 275 patients during the same period were enrolled as the external validation cohort. Patients were classified into different groups according to the presence of sarcopenia and obesity. Different inflammation indexes were evaluated to select the best predictor of overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate logistic regression were performed to investigate the associations between inflammatory indexes and SO. The inflammatory indexes with the highest predictive values and SO were selected for subgroup analyses to establish a novel classification system: the SOLMR grade. SOLMR grades identified in the multivariate Cox analysis were selected to construct novel nomograms for OS and RFS. RESULTS: SO (P<0.001) was an independent risk factor for OS and RFS. The lymphocyte-monocyte ratio (LMR) had the highest areas under the receiver operating characteristic (ROC) curves (AUCs) for OS (P<0.001) and RFS (P<0.001) and was identified as an independent factor of SO (P=0.001). SO and the LMR were selected to establish the SOLMR grade. Multivariate Cox analysis revealed that SOLMR grade was a significant independent predictor of OS (P<0.001) and RFS (P<0.001). Nomograms based on SOLMR grades were generated and accurately predicted 1-, 3- and 5-year OS and RFS in HCC patients. The C-index of the novel nomograms was higher than those of the other conventional staging systems (P<0.001). CONCLUSIONS: Both SO and the LMR were independent risk factors for OS and RFS in HCC patients after hepatectomy. The LMR was an independent factor of SO. The novel nomograms developed from the SOLMR grading system combining SO with the LMR provide good prognostic estimates of the outcomes of HCC patients.

NF-κB pathway play a role in SCD1 deficiency-induced ceramide de novo synthesis.

Stearoyl-CoA-desaturase 1 (SCD1) deficiency mediates apoptosis in colorectal cancer cells by promoting ceramide de novo synthesis. The mechanisms underlying the cross-talk between SCD1 and ceramide synthesis have not been explored. We treated colorectal cancer cells with an SCD1 inhibitor and examined the effects on gene expression, cell growth, and cellular lipid contents. The main effect of SCD1 inhibition on the fatty acid contents of colorectal cancer cells was a decrease in monounsaturated fatty acids (MUFAs). RNA sequencing (RNA-seq) showed that the most intense alteration of gene expression after SCD1 inhibition occurred in the NF-κB signaling pathway. Further experiments revealed that SCD1 inhibition resulted in increased levels of phosphorylated NF-κB p65 and increased nuclear translocation of NF-κB p65. Treatment with an NF-κB inhibitor eliminated several effects of SCD1 inhibition, mainly including overexpression of serine palmitoyltransferase1 (SPT1), elevation of dihydroceramide contents, and suppression of cell growth. Furthermore, treatment with supplemental oleate counteracted the SCD1-induced NF-κB activation and downstream effects. In summary, our data demonstrate that the NF-κB pathway plays a role in SCD1 deficiency-induced ceramide de novo synthesis in colorectal cancer cells, and that reduced MUFA levels contribute to the course.

A new strategy of laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein combined with transhepatic duct lithotomy for complex hemihepatolithiasis: A propensity score matching study.

BACKGROUND: There have been no studies on laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein combined with transhepatic duct lithotripsy for the treatment of complex hemihepatolithiasis. This study aimed to investigate the safety and efficacy of laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein combined with transhepatic duct lithotomy to treat complex hemihepatolithiasis. METHODS: The clinical data for patients who underwent laparoscopic anatomical hemihepatectomy for complex intrahepatic bile duct stones with or without common bile duct stones from January 2016 to June 2020 were prospectively collected. Patients were divided into 2 groups according to surgical approach: laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein (middle hepatic vein group) or laparoscopic anatomical hemihepatectomy not guided by the middle hepatic vein (nonmiddle hepatic vein group). The safety and short-term and long-term efficacy outcomes of the 2 groups were compared with 1:1 propensity score matching. RESULTS: With only a slightly longer operative time (P = .006), the initial and final stone residual rates in the middle hepatic vein group (n = 70) were significantly lower than those in the nonmiddle hepatic vein group (n = 70) (P = .002, P = .009). The bile leakage rate and stone recurrence rate were also significantly lower (P = .001, P = .001). CONCLUSION: Laparoscopic anatomical hemihepatectomy guided by the middle hepatic vein is safe and effective for treating intrahepatic bile duct stones and can decrease the stone residual rate, reduce the bile leakage rate and stone recurrence rate, and accelerate early recovery. However, owing to the complicated technical requirements for surgeons and anesthesiologists, use of the procedure is limited to large and experienced medical centers.

LncRNA STXBP5-AS1 suppresses stem cell-like properties of pancreatic cancer by epigenetically inhibiting neighboring androglobin gene expression.

Previous studies suggest the tumor suppressor role of long non-coding RNA (lncRNA) STXBP5-AS1 in cervical and gastric cancer, but its expression pattern and functional mechanism are still elusive in pancreatic cancer (PC). Relative expression of STXBP5-AS1 in PC both in vivo and in vitro was analyzed by real-time PCR. IC50 of Gemcitabine was determined by the MTT assay. Cell proliferation in response to drug treatment was investigated by colony formation assay. Cell apoptosis was measured by both caspase-3 activity and Annexin V/PI staining. Cell invasion capacity was scored by the transwell assay in vitro, and lung metastasis was examined with the tail vein injection assay. Cell stemness was determined in vitro by sphere formation and marker profiling, respectively, and in vivo by limited dilution of xenograft tumor incidence. Subcellular localization of STXBP5-AS1 was analyzed with fractionation PCR. Association between STXBP5-AS1 and EZH2 was investigated by RNA-immunoprecipitation. The binding of EZH2 on ADGB promoter was analyzed by chromatin immunoprecipitation. The methylation was quantified by bisulfite sequencing. We showed downregulation of STXBP5-AS1 in PC associated with poor prognosis. Ectopic STXBP5-AS1 inhibited chemoresistance and metastasis of PC cells. In addition, STXBP5-AS1 compromised stemness of PC cells. Mechanistically, STXBP5-AS1 potently recruited EZH2 and epigenetically regulated neighboring ADGB transcription, which predominantly mediated the inhibitory effects of STXBP5-AS1 on stem cell-like properties of PC cells. Our study highlights the importance of the STXBP5-EZH2-ADGB axis in chemoresistance and stem cell-like properties of PC.

The effectiveness, risks and improvement of laparoscopic pancreaticoduodenectomy during the learning curve: a propensity score-matched analysis.

BACKGROUND: Propensity score-matched analyses comparing the safety and efficacy of laparoscopic pancreaticoduodenectomy (LPD) to open pancreaticoduodenectomy (OPD) that consider the effect of the learning curve for LPD are lacking. We use Propensity score-matched to compare the safety and efficacy of LPD during the learning curve to OPD. METHODS: The medical records of 296 consecutive patients who had undergone LPD or OPD between September 2016 and August 2019 at Fujian Provincial Hospital were retrospectively reviewed. Patients treated with LPD were matched 1:1 to those treated with OPD. Calculation of propensity scores considered age, gender, body mass index (BMI), tumor location, pathology, incidence of obstructive jaundice, incidence of biliary drainage, pancreatic texture, pancreatic duct diameter, previous abdominal surgery, comorbidities, and case distribution of the surgical team. RESULTS: After propensity score matching, 196 patients were divided into two groups: 98 patients in the LPD group and 98 patients in the OPD group. LPD performed during the learning curve was associated with a longer median operative time (OT) (432 vs. 328 min, P<0.001), a higher incidence of major surgery-associated complications (32.7% vs. 14.3%, P=0.002), a higher incidence of clinically relevant pancreatic fistula (27.6% vs. 13.3%, P=0.013), and prolonged LOS (21.06 d vs. 16.94 d, P=0.033), but lower median intraoperative blood loss (200 vs. 300 mL, P<0.001) compared to OPD. Mean OT and LOS were significantly shorter in the late phase of the learning curve for LPD (P<0.001), and were similar to that for OPD. Age >60 years and a non-dilated MPD were significant predictors of clinically relevant pancreatic fistula, major surgery-associated complications, prolonged LOS and postoperative mortality at 90 days (all P<0.05). CONCLUSIONS: OT, incidence of major surgery-associated complications, and LOS were significantly increased in patients that underwent LPD, but were significantly improved during the learning curve. Elderly patients and patients with a non-dialated MPD should not be treated with LPD performed by inexperienced surgeons.

Nomogram for Predicting Long-Term Survival after Synchronous Resection for Hepatocellular Carcinoma and Inferior Vena Cava Tumor Thrombosis: A Multicenter Retrospective Study.

BACKGROUND: Although surgery for hepatocellular carcinoma (HCC) complicated with inferior vena cava tumor thrombus (IVCTT) may improve survival for some patients, prognostic markers remain elusive because of its rarity. We constructed a prognostic nomogram which predicts individualized survival benefit of curative-intent surgery for HCC patients with IVCTT. METHODS: According to abdominothoracic anatomy of inferior vena cava (IVC), IVCTT can be divided into 3 types: inferior diaphragmic (ID), superior diaphragmic (SD), and intracardiac type (IC). Data of 64 HCC patients with IVCTT who underwent curative-intent surgery between 2008 and 2015 in four centers in China were analyzed retrospectively. Univariate and multivariate Cox regression analyses were conducted to select variables for the construction of a prognostic nomogram. Predictive accuracy and discriminative ability were examined by concordance index (C-index) and calibration curve. RESULTS: Of 64 patients in the IVCTT classification, 37 (57.8%) were classified as ID type, 15 (23.4%) as SD type, and 12 (18.8%) as IC type. The 1-, 2-, 3-, and 5-year disease-specific survival (DSS) rates for patients in ID, SD, and IC groups were 94.4%, 55.6%, 71.4%, and 30.0%; 27.8%, 21.4%, 7.1%, and 0%; and 8.3%, 0%, 0%, and 0%, respectively. Independent factors included in the nomogram were ECOG performance status, AFP level ≥ 400 µg/L, tumor size ≥ 10 cm, portal vein tumor thrombosis, and IVCTT classification. The C-index of the nomogram was 0.812 (95% CI 0.761-0.873). The calibration plot for DSS probability showed excellent agreement between the prediction by nomogram and actual observation. CONCLUSIONS: Curative-intent surgery should be carefully evaluated and suggested according to our novel IVCTT classification. We have developed a visual web-based nomogram model to predict oncological prognosis of curative-intent surgery for HCC patients with IVCTT.