Publications by authors named "Meng-Chao Wu"

368 Publications

AXL Overexpression in Tumor-Derived Endothelial Cells Promotes Vessel Metastasis in Patients With Hepatocellular Carcinoma.

Front Oncol 2021 27;11:650963. Epub 2021 May 27.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Portal vein tumor thrombus (PVTT) is one of the most serious forms of hepatocellular carcinoma (HCC) vessel metastasis and has a poor survival rate. However, the molecular mechanism of PVTT has not yet been elucidated. In this study, the molecular mechanism of AXL expressed in tumor-derived endothelial cells (TECs) in vessel metastasis was investigated. High AXL expression was observed in TECs, but not in the tumor cells of HCC patients with PVTT and this was associated with poor overall survival (OS) and disease-free survival (DFS). AXL overexpression was positively associated with CD 31 expression both and . AXL promoted the cell proliferation, tube formation, and migration of both TECs and normal endothelial cells (NECs). High expression of AXL in TECs promoted the cell migration, but not the proliferation of HCC cells. Further studies demonstrated that AXL promoted cell migration and tube formation through activation of the PI3K/AKT/SOX2/DKK-1 axis. AXL overexpression in HUVECs promoted tumor growth and liver or vessel metastasis of HCC in xenograft nude mice, which could be counteracted by treatment with R428, an AXL inhibitor. R428 reduced tumor growth and CD 31 expression in HCC in PDX xenograft nude mice. Therefore, AXL over-expression in TECs promotes vessel metastasis of HCC, which indicates that AXL in TECs could be a potential therapeutic target in HCC patients with PVTT.
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http://dx.doi.org/10.3389/fonc.2021.650963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191462PMC
May 2021

Actual long-term survival in hepatocellular carcinoma patients with microvascular invasion: a multicenter study from China.

Hepatol Int 2021 Apr 5. Epub 2021 Apr 5.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, 225 Changhai Road, Shanghai, 200433, China.

Background: Microvascular invasion (MVI) is a risk factor for postoperative survival outcomes for hepatocellular carcinoma (HCC) after liver resection (LR). This study aims to investigate the actual long-term survival and its associated prognostic factors after LR for HCC patients with MVI.

Methods: This study was conducted on HCC patients with MVI who underwent LR from January 2009 to December 2012 at five major hospitals in China. The patients were divided into the 'long-term survivor group' and the 'short-term survivor group'. The clinicopathologic characteristics, perioperative data and survival outcomes were compared between these two groups. Univariate and multivariate regression analyses were performed to identify predictive factors associated with long-term survival outcomes.

Results: The study included 1517 patients with an actual 5-year survival rate of 33.3%. Multivariate regression analysis revealed that HBV DNA > 10 IU/mL, alanine aminotransferase > 44 U/L, alpha-fetoprotein > 400 ng/ml, anatomical hepatectomy, varices, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor number, satellite nodules, tumor encapsulation, wide resection margin and adjuvant transarterial chemoembolization (TACE) were independent prognostic factors associated with actual long-term survival.

Conclusions: One-third of HCC patients with MVI reached the long-term survival milestone of 5 years after resection. Anatomical hepatectomy, controlling intraoperative blood loss, a wide resection margin, and postoperative adjuvant TACE should be considered for patients to achieve better long-term survival outcomes.
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http://dx.doi.org/10.1007/s12072-021-10174-xDOI Listing
April 2021

Impact of splenomegaly and splenectomy on prognosis in hepatocellular carcinoma with portal vein tumor thrombus treated with hepatectomy.

Ann Transl Med 2021 Feb;9(3):247

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Hepatocellular carcinoma (HCC) commonly occurs in patients with splenomegaly. This study aimed to investigate the impact of splenomegaly with or without splenectomy on long-term survival of HCC patients with portal vein tumor thrombus (PVTT) treated with liver resection (LR).

Methods: HCC patients with PVTT who underwent LR from 2005 to 2012 from 6 hospitals were retrospectively studied. The long-term overall survival (OS) and recurrence-free survival (RFS) were compared between patients with or without splenomegaly, and between patients who did or did not undergo splenectomy for splenomegaly. Propensity score matching (PSM) analysis was performed to match patients in a 1:1 ratio.

Results: Of 716 HCC patients with PVTT who underwent LR, 140 patients had splenomegaly (SM group) and 576 patients had no splenomegaly (non-SM group). The SM group was further subdivided into 49 patients who underwent splenectomy (SPT group), and 91 patients who did not received splenectomy (non-SPT group). PSM matched 140 patients in the SM group, and 49 patients in the SPT group. Splenomegaly was an independent risk factor of poor RFS and OS. The OS and RFS rates were significantly better for patients in the non-SM group than the SM group (OS: P<0.001; RFS: P<0.001), and for patients in the SPT group than the non-SPT group (OS: P<0.001; RFS: P<0.001).

Conclusions: Patients who had splenomegaly had significantly worse survival in HCC patients with PVTT. Splenectomy for splenomegaly significantly improved long-term survival in these patients.
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http://dx.doi.org/10.21037/atm-20-2229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940905PMC
February 2021

Postoperative adjuvant transcatheter arterial chemoembolization improves the prognosis of patients with huge hepatocellular carcinoma.

Hepatobiliary Pancreat Dis Int 2021 Jan 5. Epub 2021 Jan 5.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Yangpu, Shanghai 200438, China. Electronic address:

Background: Surgical resection of huge hepatocellular carcinoma (HCC, ≥10 cm) is potentially curative. More adjuvant treatments are needed to reduce relapses in these patients. We evaluated the influence of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) on the prognosis of huge HCC.

Methods: Data from consecutive patients who underwent curative resection for huge HCC in our center were retrospectively collected. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients who did and did not undergo PA-TACE. Propensity score matching (PSM) was used.

Results: Among the 255 enrolled patients, 93 underwent PA-TACE. The clinical outcomes were significantly better in the PA-TACE group than those in the non PA-TACE group (5-year RFS rate: 33.5% vs. 18.0%; 5-year OS rate: 47.0% vs. 28.0%, all P<0.001). After PSM, similar results were obtained (5-year RFS rate: 28.8% vs. 17.6%, P<0.001; 5-year OS rate: 42.5% vs. 25.0%, P=0.004). PA-TACE decreased the possibility of early recurrence (<2 years, crude cohort: P<0.001, PSM cohort: P<0.001) but not late recurrence (≥2 years, crude cohort: P=0.692, PSM cohort: P=0.325). Multivariable Cox regression analysis suggested that PA-TACE was an independent protective factor prolonging early RFS, RFS and OS.

Conclusion: PA-TACE is a safe intervention for huge HCC patients after liver resection and improves outcomes.
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http://dx.doi.org/10.1016/j.hbpd.2020.12.018DOI Listing
January 2021

Extracellular-vesicles delivered tumor-specific sequential nanocatalysts can be used for MRI-informed nanocatalytic Therapy of hepatocellular carcinoma.

Theranostics 2021 1;11(1):64-78. Epub 2021 Jan 1.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, P. R. China.

Conventional therapeutic strategies for advanced hepatocellular carcinoma (HCC) remains a great challenge, therefore the alternative therapeutic modality for specific and efficient HCC suppression is urgently needed. In this work, HCC-derived extracellular vesicles (EVs) were applied as surface nanocarrier for sequential nanocatalysts [email protected] ([email protected]) of tumor-specific and cascade nanocatalytic therapy against HCC. By enhancing the intracellular endocytosis through arginine-glycine-aspartic acid (RGD)-targeting effect and membrane fusion, sequential nanocatalysts led to more efficient treatment in the HCC tumor region in a shorter period of time. Through glucose consumption as catalyzed by the loaded glucose oxidase (GOD) to overproduce hydrogen peroxide (HO), highly toxic hydroxyl radicals were generated by Fenton-like reaction as catalyzed by ESIONs, which was achieved under the mildly acidic tumor microenvironment, enabling the stimuli of the apoptosis and necrosis of HCC cells. This strategy demonstrated the high active-targeting capability of [email protected] into HCC, achieving highly efficient tumor suppression both and . In addition, the as-synthesized nanoreactor could act as a desirable nanoscale contrast agent for magnetic resonance imaging, which exhibited desirable imaging capability during the sequential nanocatalytic treatment. This application of surface-engineering EVs not only proves the high-performance catalytic therapeutic modality of [email protected] for HCC, but also broadens the versatile bio-applications of EVs.
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http://dx.doi.org/10.7150/thno.46124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681081PMC
January 2021

A new classification for hepatocellular carcinoma with hepatic vein tumor thrombus.

Hepatobiliary Surg Nutr 2020 Dec;9(6):717-728

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Hepatic vein tumor thrombus (HVTT) is a significant poor risk factor for survival outcomes in hepatocellular carcinoma (HCC) patients. Currently, the widely used international staging systems for HCC are not refined enough to evaluate prognosis for these patients. A new classification for macroscopic HVTT was established, aiming to better predict prognosis.

Methods: This study included 437 consecutive HCC patients with HVTT who underwent different treatments. Overall survival (OS) and time-dependent receiver operating characteristic (ROC) curve area analysis were used to determine the prognostic capacities of the new classification when compared with the different currently used staging systems.

Results: The new HVTT classification was defined as: type I, tumor thrombosis involving hepatic vein (HV), including microvascular invasion; type II, tumor thrombosis involving the retrohepatic segment of inferior vena cava; and type III, tumor thrombosis involving the supradiaphragmatic segment of inferior vena cava. The numbers (percentages) of patients with types I, II, and III HVTT in the new classification were 146 (33.4%), 143 (32.7%), and 148 (33.9%), respectively. The 1-, 2-, and 3-year OS rates for types I to III HVTT were 79.5%, 58.6%, and 29.1%; 54.8%, 23.3%, and 13.8%; and 24.0%, 10.0%, and 2.1%, respectively. The time-dependent-ROC curve area analysis demonstrated that the predicting capacity of the new HVTT classification was significantly better than any other staging systems.

Conclusions: A new HVTT classification was established to predict prognosis of HCC patients with HVTT who underwent different treatments. This classification was superior to, and it may serve as a supplement to, the commonly used staging systems.
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http://dx.doi.org/10.21037/hbsn.2019.10.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720043PMC
December 2020

A novel role of Krüppel-like factor 8 as an apoptosis repressor in hepatocellular carcinoma.

Cancer Cell Int 2020 28;20:422. Epub 2020 Aug 28.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438 China.

Background: Krüppel-like factor 8 (KLF8), a cancer-promoting factor that regulates critical gene transcription and cellular cancer-related events, has been implicated in tumor development and progression. However, the functional role of KLF8 in the pathogenesis of hepatocellular carcinoma (HCC) remains largely unknown.

Methods: The gene expression patterns and genome-wide regulatory profiles of HCC cells after KLF8 knockout were analyzed by using RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) of histone H3 lysine 27 acetylation (H3K27ac) combined with bioinformatics analysis. Transcription factor-binding motifs that recognized by KLF8 were evaluated by motif analysis. For the predicted target genes, transcriptional changes were examined by ChIP, and loss of function experiments were conducted by siRNA transfection.

Results: KLF8 functioned as a transcription repressor in HCC and mainly regulated apoptotic-related genes directly. A total of 1,816 differentially expressed genes after KLF8 knockout were identified and significantly corresponded to global changes in H3K27ac status. Furthermore, two predicted target genes, high-mobility group AT-hook 2 (HMGA2) and matrix metalloproteinase 7 (MMP7), were identified as important participants in KLF8-mediated anti-apoptotic effect in HCC. Knockout of KLF8 enhanced cell apoptosis process and caused increase in the associated H3K27ac, whereas suppression HMGA2 or MMP7 attenuated these biological effects.

Conclusions: Our work suggests a novel role and mechanism for KLF8 in the regulation of cell apoptosis in HCC and facilitates the discovery of potential therapeutic targets for HCC treatment.
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http://dx.doi.org/10.1186/s12935-020-01513-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456055PMC
August 2020

Major Hepatectomy in Elderly Patients with Large Hepatocellular Carcinoma: A Multicenter Retrospective Observational Study.

Cancer Manag Res 2020 9;12:5607-5618. Epub 2020 Jul 9.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Harbin Medical University, Heilongjiang, People's Republic of China.

Background: With an increase in life expectancy and improvement of surgical safety, more elderly patients with hepatocellular carcinoma (HCC), even with large tumors, are now considered for hepatectomy. This study aimed to clarify the impact of age on short- and long-term outcomes after major hepatectomy (≥3 segments) for large HCC (≥5 cm).

Patients And Methods: Using a multicenter database, patients who underwent curative-intent major hepatectomy for large HCC between 2006 and 2016 were identified. Postoperative morbidity and mortality, overall survival (OS) and recurrence-free survival (RFS) were compared between the elderly (≥65 years) and younger (<65 years) patients. Univariable and multivariable Cox-regression analyses were performed to identify the risk factors of OS and RFS in the entire and elderly cohorts, respectively.

Results: Of 830 patients, 92 (11.1%) and 738 (88.9%) were elderly and younger patients, respectively. There were no significant differences in postoperative 30-day mortality and morbidity between the two groups (5.4% vs 2.6% and 43.5% vs 38.3%, both P>0.05). The 5-year OS and RFS rates in elderly patients were also comparable to younger patients (35.0% vs 33.2% and 20.0% vs 20.8%, both P>0.05). In the entire cohort, multivariable Cox-regression analyses identified that old age was not independently associated with OS and RFS. However, in the elderly cohort, preoperative alpha-fetoprotein level >400 μg/L, multiple tumors, macrovascular invasion and microvascular invasion were independently associated with decreased OS and RFS.

Conclusion: Carefully selected elderly patients benefited from major hepatectomy for large HCC as much as younger patients, and their long-term prognosis was determined by preoperative alpha-fetoprotein level, tumor number and presence of macro- or micro-vascular invasion.
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http://dx.doi.org/10.2147/CMAR.S258150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7358072PMC
July 2020

Impact of Surgical Margin on the Prognosis of Early Hepatocellular Carcinoma (≤5 cm): A Propensity Score Matching Analysis.

Front Med (Lausanne) 2020 7;7:139. Epub 2020 May 7.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.

The influence of surgical margin on the prognosis of patients with early solitary hepatocellular carcinoma (HCC) (≤5 cm) is undetermined. The data of 904 patients with early solitary HCC who underwent liver resection were collected for recurrence-free survival (RFS) and overall survival (OS). Propensity score matching (PSM) was performed to balance the potential bias. Log-rank tests showed that 2 mm was the best cutoff value to discriminate the prognosis of early HCC. Liver resection with a >2 mm surgical margin distance (wide-margin group) led to better 5-year RFS and OS rate compared with liver resection with a ≤2 mm surgical margin distance (narrow-margin group) among patients both before (RFS: 59.1% vs. 39.6%, < 0.001; OS: 85.3% vs. 73.7%, < 0.001) and after PSM (RFS: 56.3% vs. 41.0%, < 0.001; OS: 83.0% vs. 75.0%, = 0.010). Subgroup analysis showed that a wide-margin resection significantly improved the prognosis of patients with microvascular invasion (RFS: < 0.001; OS: = 0.001) and patients without liver cirrhosis (RFS: < 0.001; OS: = 0.001) after PSM. Multivariable Cox regression analysis revealed that narrow-margin resection is associated with poorer RFS [hazard ratio (HR) = 1.781, < 0.001), OS (HR = 1.935, < 0.001], and early recurrence (HR = 1.925, < 0.001). A wide-margin resection resulted in better clinical outcomes than a narrow-margin resection among patients with early solitary HCC, especially for those with microvascular invasion and without cirrhosis. An individual strategy of surgical margin should be formulated preoperation according to both tumor factors and background liver factors.
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http://dx.doi.org/10.3389/fmed.2020.00139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232563PMC
May 2020

Early and Late Recurrence of Hepatitis B Virus-Associated Hepatocellular Carcinoma.

Oncologist 2020 10 9;25(10):e1541-e1551. Epub 2020 Jun 9.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China.

Background: Survival after liver resection of hepatocellular carcinoma (HCC) remains poor because of a high incidence of recurrence. We sought to investigate risk factors, patterns, and long-term prognosis among patients with early and late recurrence after liver resection for hepatitis B virus (HBV)-associated HCC.

Methods: Data of consecutive patients undergoing curative resection for HBV-associated HCC were analyzed. According to the time to recurrence after surgery, recurrence was divided into early (≤2 years) and late recurrence (>2 years). Characteristics, patterns of initial recurrence, and postrecurrence survival (PRS) were compared between patients with early and late recurrence. Risk factors of early and late recurrence and predictors of PRS were identified by univariable and multivariable Cox regression analyses.

Results: Among 894 patients, 322 (36.0%) and 282 (31.5%) developed early and late recurrence, respectively. On multivariable analyses, preoperative HBV-DNA >10 copies/mL was associated with both early and late recurrence, whereas postoperative no/irregular antiviral therapy was associated with late recurrence. Compared with patients with late recurrence, patients with early recurrence had a lower proportion of intrahepatic-only recurrence (72.0% vs. 91.1%, p < .001), as well as a lower chance of receiving potentially curative treatments for recurrence (33.9% vs. 50.7%, p < .001) and a worse median PRS (19.1 vs. 37.5 months, p < .001). Multivariable analysis demonstrated that early recurrence was independently associated with worse PRS (hazard ratio, 1.361; 95% confidence interval, 1.094-1.692; p = .006).

Conclusion: Although risk factors associated with early recurrence and late recurrence were different, a high preoperative HBV-DNA load was an independent hepatitis-related risk for both early and late recurrence. Early recurrence was associated with worse postrecurrence survival among patients with recurrence.

Implications For Practice: Liver resection is the main curative treatment for hepatocellular carcinoma (HCC), but postoperative survival remains poor because of high recurrence rates. This study investigated the risk factors and patterns of early and late recurrence and found that a high preoperative hepatitis B virus (HBV) DNA load was an independent hepatitis-related risk factor for both. Early recurrence was also independently associated with worse postrecurrence survival. These data may provide insights into different biological origin and behavior of early versus late recurrence after resection for HBV-associated HCC, which could be helpful to make individualized treatment decision for recurrent HCC, as well as strategies for surveillance recurrence after resection.
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http://dx.doi.org/10.1634/theoncologist.2019-0944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543359PMC
October 2020

A novel online calculator to predict perioperative blood transfusion in patients undergoing liver resection for hepatocellular carcinoma: an international multicenter study.

HPB (Oxford) 2020 12 25;22(12):1711-1721. Epub 2020 Apr 25.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Naval Medical University), Shanghai, China. Electronic address:

Background: To develop an easy-to-use model to predict the probability of perioperative blood transfusion (PBT) in patients undergoing liver resection for hepatocellular carcinoma (HCC).

Method: 878 patients from Eastern Hepatobiliary Surgery Hospital of Shanghai were enrolled in the training cohort, while 691 patients from Tongji Hospital of Wuhan and 364 patients from two hospitals from Europe and America served as the Eastern and Western external validation cohorts, respectively. Independent predictors of PBT were identified and used for the nomogram construction. The predictive performance of the model was assessed using the concordance index (C-index) and calibration plot, and externally validated using the two independent cohorts. This model was compared with four currently available prediction risk scores.

Results: Eight preoperative variables were identified as independent predictors of PBT, which were incorporated into the new nomogram model, with a C-index of 0.833 and a well-fitted calibration plot. The nomogram performed well on the externally Eastern and Western validation cohorts (C-indexes: 0.786 and 0.777). The discriminatory ability of the nomogram was superior to the four currently available prediction scores (C-indexes: 0.833 vs. 0.671-0.770). The nomogram was programmed into an online calculator, which is available at http://www.asapcalculate.top/Cal3_en.html.

Conclusion: A nomogram model, using an easy-to-access website, can be used to calculate the PBT risk and identify which patients undergoing HCC resection are at high risks of PBT and can benefit most by using blood conservation techniques.
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http://dx.doi.org/10.1016/j.hpb.2020.03.018DOI Listing
December 2020

Impact of iatrogenic biliary injury during laparoscopic cholecystectomy on surgeon's mental distress: a nationwide survey from China.

HPB (Oxford) 2020 12 10;22(12):1722-1731. Epub 2020 Apr 10.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai. Electronic address:

Background: Iatrogenic biliary injury (IBI) following laparoscopic cholecystectomy (LC) is the most serious iatrogenic complications. Little is known whether LC-IBI would lead to surgeon's severe mental distress (SMD).

Methods: A cross-sectional survey in the form of electronic questionnaire was conducted among Chinese general surgeons who have caused LC-IBI. The six collected clinical features relating to mental distress included: 1) feeling burnout, anxiety, or depression, 2) avoiding performing LC, 3) having physical reactions when recalling the incidence, 4) having the urge to quit surgery, 5) taking psychiatric medications, and 6) seeking professional psychological counseling. Univariable and multivariable analyses were performed to identify risk factors of SMD, which was defined as meeting ≥3 of the above-mentioned clinical features.

Results: Among 1466 surveyed surgeons, 1236 (84.3%) experienced mental distress following LC-IBI, and nearly half (49.7%, 614/1236) had SMD. Multivariable analyses demonstrated that surgeons from non-university affiliated hospitals (OR:1.873), patients who required multiple repair operations (OR:4.075), patients who required hepaticojejunostomy/partial hepatectomy (OR:1.859), existing lawsuit litigation (OR:10.491), existing violent doctor-patient conflicts (OR:4.995), needing surgeons' personal compensation (OR:2.531), and additional administrative punishment by hospitals (OR:2.324) were independent risk factors of surgeon's SMD.

Conclusion: Four out of five surgeons experienced mental distress following LC-IBI, and nearly half had SMD. Several independent risk factors of SMD were identified, which could help to make strategies to improve surgeons' mental well-being.
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http://dx.doi.org/10.1016/j.hpb.2020.03.019DOI Listing
December 2020

Multicenter analysis of long-term oncologic outcomes of hepatectomy for elderly patients with hepatocellular carcinoma.

HPB (Oxford) 2020 09 21;22(9):1314-1323. Epub 2020 Jan 21.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: Aging of the population and prolonged life expectancy have significantly increased the number of elderly patients undergoing hepatectomy for hepatocellular carcinoma (HCC). However, potential benefits, especially long-term oncologic outcomes of hepatectomy for elderly patients with HCC remain unclear.

Method: Patients treated with curative-intent hepatectomy for HCC in 8 Chinese hospitals were enrolled. Patients were divided into the elderly (≥70 years old) and younger (<70 years old) groups. Overall survival (OS), cancer-specific survival (CSS), and time-to-recurrence (TTR) were compared. Risk factors of CSS and TTR were evaluated by univariable and multivariable competing-risk regression analyses.

Results: Of 2134 patients, 259 (12.1%) and 1875 (87.9%) were elderly and younger aged, respectively. Postoperative 30-day and 90-day mortality was comparable among elderly and younger patients. Compared with younger patients, the elderly had a worse 5-year OS (49.4% vs. 55.3%, P = 0.032), yet a better 5-year CCS (74.5% vs. 61.0%, P = 0.005) and a lower 5-year TTR (33.7% vs. 44.9%, P < 0.001), respectively. Multivariable analyses identified that elder age was independently associated with more favorable CSS (HR 0.74, 95%CI 0.58-0.90, P = 0.011) and TTR (0.69, 0.53-0.88, P < 0.001) but was not associated with OS (P = 0.136).

Conclusions: Age by itself is not a contraindication to surgery, and selected elderly patients with HCC can benefit from hepatectomy. Compared with younger patients, elderly patients have noninferior oncologic outcomes following hepatectomy for HCC.
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http://dx.doi.org/10.1016/j.hpb.2019.12.006DOI Listing
September 2020

Repeat hepatectomy for patients with early and late recurrence of hepatocellular carcinoma: A multicenter propensity score matching analysis.

Surgery 2021 04 23;169(4):911-920. Epub 2019 Dec 23.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China. Electronic address:

Background: Repeat hepatectomy is a feasible treatment modality for intrahepatic recurrence after hepatectomy of hepatocellular carcinoma, yet the survival benefit remains ill-defined. The objective of the current study was to define long-term, oncologic outcomes after repeat hepatectomy among patients with early and late recurrence.

Methods: Patients undergoing curative-intent repeat hepatectomy for recurrent hepatocellular carcinoma were identified using a multi-intuitional database. Early and late recurrence was defined by setting 1 year after initial hepatectomy as the cutoff value. Patient clinical characteristics, overall survival, and disease-free survival were compared among patients with early and late recurrence before and after propensity score matching.

Results: Among all the patients, 81 had early recurrence and 129 had late recurrence from which 74 matched pairs were included in the propensity score matching analytic cohort. Before propensity score matching, 5-year overall survival and disease-free survival after resection of an early recurrence were 41.7% and 17.9%, respectively, which were worse compared with patients who had resection of a late recurrence (57.0% and 39.4%, both P < .01). After propensity score matching, 5-year overall survival and disease-free survival among patients with early recurrence were worse compared with patients with late recurrence (41.0% and 19.2% vs 64.3% and 43.2%, both P < .01). After adjustment for other confounding factors on multivariable Cox-regression analysis, early recurrence remained independently associated with decreased overall survival and disease-free survival (hazard ratio 2.22, 95% confidence interval 1.35-3.34, P = .001; hazard ratio 1.86, 95% confidence 1.26-2.74, P = .002).

Conclusion: Repeat hepatectomy for early recurrence was associated with worse overall survival and disease-free survival compared with late recurrence. These data may help inform patients and selection of patients being considered for repeat hepatectomy of recurrent hepatocellular carcinoma.
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http://dx.doi.org/10.1016/j.surg.2019.11.005DOI Listing
April 2021

Liver Resection Is Justified in Patients with BCLC Intermediate Stage Hepatocellular Carcinoma without Microvascular Invasion.

J Gastrointest Surg 2020 12 25;24(12):2737-2747. Epub 2019 Nov 25.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, China.

Background: Large, multinodular (> 3 nodules and/or > 3 cm) hepatocellular carcinoma (HCC) is not an indication for liver resection based on the Barcelona Clinic Liver Cancer (BCLC) staging classification. We hypothesize that microvascular invasion (MVI) is a strong indication for surgery in these patients.

Methods: Between December 2009 and December 2010, a retrospective cohort of the patients with BCLC intermediate stage HCC undergoing surgical resection at Eastern Hepatobiliary Surgery Hospital was analyzed. Propensity score matching (PSM) was conducted to balance the patients with regard to their baseline characteristics. Survival analysis was performed according to the Kaplan-Meier method. Logistic regression was conducted to identify the predictors of MVI. Risk factors were evaluated using the Cox proportional hazards model.

Results: Among 323 patients, the MVI-negative group (26.0%) had a more favorable prognosis than did the MVI-positive group (5-year recurrence-free survival: 25.2% vs. 7.8%; 5-year overall survival: 49.5% vs. 24.0%). Similar results were identified after PSM. Compared with MVI-negative patients, MVI-positive patients experienced more early recurrence (< 2 years, P = 0.006), multinodular recurrence (P = 0.004), and extrahepatic recurrence (P = 0.026). Total bilirubin levels > 17.1 μmol/L, alpha fetal protein levels > 400 ng/mL, the presence of > 2 nodules, and the lack of a capsule were independent predictors of MVI.

Conclusions: In BCLC intermediate stage HCC, MVI predicted an adverse recurrence pattern and poor prognosis and has the potential to be used as a reference index when deciding whether to operate. Factors predictive of MVI could assist in choosing preoperative treatment and postoperative surveillance.
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http://dx.doi.org/10.1007/s11605-019-04251-8DOI Listing
December 2020

The impact of portal vein tumor thrombus on long-term survival after liver resection for primary hepatic malignancy.

HPB (Oxford) 2020 07 13;22(7):1025-1033. Epub 2019 Nov 13.

The Medical College of Soochow University, Jiangsu, China; Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: The aim of this study was to evaluate the effect of portal vein tumor thrombus (PVTT) on the prognosis of patients undergoing liver resection (LR) for primary liver malignancies (PLC).

Methods: The recurrence-free survival (RFS) and overall survival (OS) for patients undergoing LR with and without PVTT for three primary liver malignancies, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepato-cholangio carcinoma (CHC) were compared using the Kaplan-Meier method and Cox regression analysis.

Results: In total, 3775 patients with PLC who underwent LR were included in this study. The incidence of PVTT in patients undergoing LR with HCC, IHC and CHC were 46%, 20%, and 17%, respectively. The median RFS and OS were significantly better for patients with HCC as compared to ICC or CHC (16 vs 11 vs 13 months; 21 vs 16 vs 18 months, respectively; P < 0.001). However, the presence of PVTT resulted in similarly poor RFS and OS in these 3 subgroups of patients (9 vs 8 vs 8 months, P = 0.062; 14 vs 13 vs 12 months, respectively, P = 0.052).

Conclusion: Although the prognosis of patients with PLC varied by histological subtype, once PVTT occurred, survival outcomes after LR were similarly poor across all three subgroups.
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http://dx.doi.org/10.1016/j.hpb.2019.10.2439DOI Listing
July 2020

Does microvascular invasion in Barcelona Clinic Liver Cancer stage A multinodular hepatocellular carcinoma indicate early-stage behavior?

Ann Transl Med 2019 Sep;7(18):428

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai 200438, China.

Background: To identify the impact of tumor number on Barcelona Clinic Liver Cancer (BCLC) early-stage hepatocellular carcinoma (HCC) and the impact of microvascular invasion (MVI) on multinodular HCC (MHCC).

Methods: We retrospectively analyzed 1,548 patients who had early-stage HCC [solitary HCC (SHCC, n=1,481) and MHCC (n=67)], according to the BCLC classification, after curative resection. Recurrence-free survival (RFS) and overall survival (OS) were compared. Propensity score matching (PSM) was used to balance potential confounding factors.

Results: Both before and after PSM, significant differences were noted between the MHCC group and the SHCC group in RFS but not in OS. For the PSM cohort, the 5-year RFS rates were 7.5% and 41.2% for the MVI-positive MHCC group and the SHCC group, respectively (P<0.001). The 5-year OS rates were 48.9% and 75.2% for the MVI-positive MHCC group and the SHCC group, respectively (P=0.017). The RFS and OS were not significantly different between the MVI-negative MHCC group and the SHCC group. MVI (P=0.029) and multiple nodules (P=0.029) were associated with early recurrence.

Conclusions: The presence of MVI in BCLC early-stage MHCC was highly suggestive of a poor prognosis and should not be classified as early-stage biological behavior.
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http://dx.doi.org/10.21037/atm.2019.08.114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6803243PMC
September 2019

Defining and predicting early recurrence after liver resection of hepatocellular carcinoma: a multi-institutional study.

HPB (Oxford) 2020 05 10;22(5):677-689. Epub 2019 Oct 10.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: A clear definition of "early recurrence" after hepatocellular carcinoma (HCC) resection is still lacking. This study aimed to determine the optimal cutoff between early and late HCC recurrence, and develop nomograms for pre- and postoperative prediction of early recurrence.

Methods: Patients undergoing HCC resection were identified from a multi-institutional Chinese database. Minimum P-value approach was adopted to calculate optimal cut-off to define early recurrence. Pre- and postoperative risk factors for early recurrence were identified and further used for nomogram construction. The results were externally validated by a Western cohort.

Results: Among 1501 patients identified, 539 (35.9%) were recurrence-free. The optimal length to distinguish between early (n = 340, 35.3%) and late recurrence (n = 622, 64.7%) was 8 months. Multivariable logistic regression analyses identified 5 preoperative and 8 postoperative factors for early recurrence, which were further incorporated into preoperative and postoperative nomograms (C-index: 0.785 and 0.834). The calibration plots for the probability of early recurrence fitted well. The nomogram performance was maintained using the validation dataset (C-index: 0.777 for preoperative prediction and 0.842 for postoperative prediction).

Conclusions: An interval of 8 months was the optimal threshold for defining early HCC recurrence. The two web-based nomograms have been published to allow accurate pre- and postoperative prediction of early recurrence. These may offer useful guidance for individual treatment or follow up for patients with resectable HCC.
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http://dx.doi.org/10.1016/j.hpb.2019.09.006DOI Listing
May 2020

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study.

Eur J Surg Oncol 2019 Dec 12;45(12):2360-2368. Epub 2019 Sep 12.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: The Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.

Methods: 1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.

Results: Overall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111-1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034-1.358, P = 0.007).

Conclusions: Patients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.
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http://dx.doi.org/10.1016/j.ejso.2019.09.009DOI Listing
December 2019

Preoperative transcatheter arterial chemoembolization for surgical resection of huge hepatocellular carcinoma (≥ 10 cm): a multicenter propensity matching analysis.

Hepatol Int 2019 Nov 5;13(6):736-747. Epub 2019 Sep 5.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), No. 225, Changhai Road, Shanghai, 200438, China.

Background And Aims: Surgical resection for hepatocellular carcinoma (HCC) is potentially curative, but long-term survival remains unsatisfactory. There is currently no effective neoadjuvant or adjuvant therapy for HCC. We sought to evaluate the impact of preoperative transcatheter arterial chemoembolization (TACE) on long-term prognosis after surgical resection of huge HCCs (≥ 10 cm).

Methods: Using a multicenter database, consecutive patients who underwent curative-intent resection for huge HCC without macrovascular invasion between 2004 and 2014 were identified. The association between preoperative TACE with perioperative outcomes, long-term overall survival (OS), and recurrence-free survival (RFS) was assessed before and after propensity score matching (PSM).

Results: Among the 377 enrolled patients, 88 patients (23.3%) received preoperative TACE. The incidence of perioperative mortality and morbidity was comparable among patients who did and did not undergo preoperative TACE (3.4% vs. 2.4%, p= 0.704, and 33.0% vs. 31.1%, p= 0.749, respectively). PSM analysis created 84 matched pairs of patients. In examining the entire cohort as well as the PSM cohort, median OS (overall cohort: 32.8 vs. 22.3 months, p= 0.035, and PSM only: 32.8 vs. 18.1 months, p= 0.023, respectively) and RFS (12.9 vs. 6.4 months, p= 0.016, and 12.9 vs. 4.1 months, p= 0.009, respectively) were better among patients who underwent preoperative TACE vs. patients who did not. After adjustment for other confounding factors on multivariable analyses, preoperative TACE remained independently associated with a favorable OS and RFS after the resection of huge HCC.

Conclusion: Preoperative TACE did not increase perioperative morbidity or mortality, yet was associated with an improved OS and RFS after liver resection of huge HCC (≥ 10 cm).
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http://dx.doi.org/10.1007/s12072-019-09981-0DOI Listing
November 2019

Association between body mass index and postoperative morbidity after liver resection of hepatocellular carcinoma: A multicenter study of 1,324 patients.

HPB (Oxford) 2020 02 9;22(2):289-297. Epub 2019 Aug 9.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. Electronic address:

Background: Morbidity remains a common problem following hepatic resection. The aim of this study was to investigate the association between preoperative body mass index (BMI) and morbidity in patients undergoing liver resection for hepatocellular carcinoma (HCC).

Methods: Patients were divided into three groups according to preoperative BMI: low-BMI (≤18.4 kg/m), normal-BMI (18.5-24.9 kg/m) and high-BMI (≥25.0 kg/m). Baseline characteristics, operative variables, postoperative 30-day mortality and morbidity were compared. Univariable and multivariable analyses were performed to identify independent risk factors associated with postoperative morbidity.

Results: Among 1324 patients, 108 (8.2%), 733 (55.4%), and 483 (36.5%) were low-BMI, normal-BMI, and high-BMI, respectively. There were no differences in postoperative 30-day mortality among patients based on BMI (P = 0.199). Postoperative 30-day morbidity was, however, higher in low-BMI and high-BMI patients versus patients with a normal-BMI (33.3% and 32.1% vs. 22.9%, P = 0.018 and P < 0.001, respectively). Following multivariable analysis low-BMI and high-BMI remained independently associated with an increased risk of postoperative morbidity (OR: 1.701, 95%CI: 1.060-2.729, P = 0.028, and OR: 1.491, 95%CI: 1.131-1.966, P = 0.005, respectively). Similar results were noted in the incidence of postoperative 30-day surgical site infection (SSI).

Conclusion: Compared with normal-BMI patients, low-BMI and high-BMI patients had higher postoperative morbidity, including a higher incidence of SSI after liver resection for HCC.
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http://dx.doi.org/10.1016/j.hpb.2019.06.021DOI Listing
February 2020

Impact of Surveillance in Chronic Hepatitis B Patients on Long-Term Outcomes After Curative Liver Resection for Hepatocellular Carcinoma.

J Gastrointest Surg 2020 09 6;24(9):1987-1995. Epub 2019 Aug 6.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, No 225, Changhai Road, Shanghai, 200438, China.

Background: Clinical guidelines recommend surveillance in high-risk population to early detect hepatocellular carcinoma (HCC), when curative treatment such as liver resection can be applied. However, it is largely unknown whether surveillance would provide long-term survival benefits to these high-risk patients who have received curative liver resection for HCC.

Methods: A prospectively maintained database on patients with chronic hepatitis B infection who underwent curative liver resection for HCC from 2003 to 2014 was reviewed. Patients' overall survival and recurrence were compared between the groups of patients whose HCCs were diagnosed by surveillance or non-surveillance, as well as between the groups of patients operated in the first (2003-2008) and second (2009-2014) 6-year periods.

Results: Of 1075 chronic hepatitis B patients with HCC, 452 (42.0%) patients were diagnosed by preoperative surveillance. Compared with the non-surveillance group, the OS and RFS rates were significantly better in the surveillance group (both P < 0.001). Surveillance was associated with a 55% decrease in the overall survival risk and a 48% decrease in the recurrence risk (HR 0.45, 95% CI 0.38-0.53, and HR 0.52, 95% CI 0.44-0.61). Compared with the first period, a significant reduction of 12% and 19% in the overall death and recurrence risks, respectively, was observed in the second period (HR 0.88, 95% CI 0.78-0.97, and HR 0.81, 95% CI 0.70-0.95).

Conclusion: Surveillance for HCC was associated with favorable long-term overall and recurrence-free survival rates after curative liver resection of HCC in patients with chronic hepatitis B.
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http://dx.doi.org/10.1007/s11605-019-04295-wDOI Listing
September 2020

Tissue and serum metabolomic phenotyping for diagnosis and prognosis of hepatocellular carcinoma.

Int J Cancer 2020 03 13;146(6):1741-1753. Epub 2019 Aug 13.

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

More than two-thirds of patients with hepatocellular carcinoma (HCC) cannot receive curative therapy and have poor survival due to late diagnosis and few prognostic directions. In our study, nontargeted and targeted metabolomics analyses were conducted by liquid chromatography-mass spectrometry to characterize metabolic features of HCC and identify diagnostic and prognostic biomarker candidate incorporating liver tissue and serum metabolites. A total of 552 subjects, including 432 with liver tissue and 120 with serum specimens, were recruited in China. In the discovery cohort, a series of 138 metabolites were identified to discriminate HCC tissues from matched nontumor tissues. Retinol presented with the highest area under the curve (AUC) of 0.991 and associated with Edmondson grade. In the validation cohort, all metabolites in retinol metabolism pathway were examined and the levels of retinol and retinal in tumor tissue and serum decreased in the order of normal to cirrhosis to HCC of Edmondson Grades I to IV. Retinol and retinal levels could also differentiate between HCC and cirrhosis, with AUCs of 0.996 and 0.994, respectively, in tissue and 0.812 and 0.744, respectively, in serum. The AUC of the combined retinol and retinal panel in serum was 0.852. Univariate and multivariate Cox regression identified this panel as an independent predictor for HCC and showed that low expression of retinol and retinal correlated with decreased survival time. In conclusion, the retinol metabolic signature had considerable diagnostic and prognostic value for identifying HCC patients who would benefit from prompt therapy and optimal prognostic direction.
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http://dx.doi.org/10.1002/ijc.32599DOI Listing
March 2020

Association of Preoperative Hypercoagulability with Poor Prognosis in Hepatocellular Carcinoma Patients with Microvascular Invasion After Liver Resection: A Multicenter Study.

Ann Surg Oncol 2019 Nov 18;26(12):4117-4125. Epub 2019 Jul 18.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Microvascular invasion (MVI) predicts poor prognosis in patients with hepatocellular carcinoma (HCC). HCC patients with hypercoagulability are prone to develop thrombosis; however, the relationship between preoperative coagulability state, as reflected by the international normalized ratio (INR) level, and MVI remains unclear.

Methods: From January 2009 to December 2012, HCC patients who underwent R0 liver resection (LR) from four cancer centers entered into this study. The overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method and Cox regression analysis.

Results: Of the 2509 HCC patients who were included into this study, 1104 were found to have MVI in the resected specimens. These patients were divided into the low (n = 151), normal (n = 796), and high (n = 157) INR subgroups based on the preoperative INR levels. The low INR subgroup had a significantly higher incidence of MVI than the normal or high INR subgroups (61.6% vs. 41.6% vs. 44.6%; p < 0.001). HCC patients with MVI were significantly more likely to have a low preoperative INR level (p < 0.001); the INR level (p < 0.001) was an independent risk factor of OS and RFS. HCC patients with MVI in the low INR subgroup had significantly worse RFS and OS than the normal or high INR subgroups (median RFS 13.5 vs. 20.2 vs. 21.6 months, p < 0.001; median OS 35.5 vs. 59.5 vs. 57.0 months, p < 0.001).

Conclusions: Preoperative hypercoagulability was associated with poor long-term prognosis in HCC patients with MVI after R0 LR.
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http://dx.doi.org/10.1245/s10434-019-07504-7DOI Listing
November 2019

An Eastern Hepatobiliary Surgery Hospital Microvascular Invasion Scoring System in Predicting Prognosis of Patients with Hepatocellular Carcinoma and Microvascular Invasion After R0 Liver Resection: A Large-Scale, Multicenter Study.

Oncologist 2019 12 28;24(12):e1476-e1488. Epub 2019 May 28.

Departments of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China

Background: Microvascular invasion (MVI) is associated with poor postoperative survival outcomes in patients with hepatocellular carcinoma (HCC). An Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis in patients with HCC with MVI after R0 liver resection (LR) and to supplement the most commonly used classification systems.

Materials And Methods: Patients with HCC with MVI who underwent R0 LR as an initial therapy were included. The EHBH-MVI score was developed from a retrospective cohort from 2003 to 2009 to form the training cohort. The variables associated with overall survival (OS) on univariate analysis were subsequently investigated using the log-rank test, and the EHBH-MVI score was developed using the Cox regression model. It was validated using an internal prospective cohort from 2011 to 2013 as well as three independent external validation cohorts.

Results: There were 1,033 patients in the training cohort; 322 patients in the prospective internal validation cohort; and 493, 282, and 149 patients in the three external validation cohorts, respectively. The score was developed using the following factors: α-fetoprotein level, tumor encapsulation, tumor diameter, hepatitis B e antigen positivity, hepatitis B virus DNA load, tumor number, and gastric fundal/esophageal varicosity. The score differentiated two groups of patients (≤4, >4 points) with distinct long-term prognoses outcomes (median OS, 55.8 vs. 19.6 months; < .001). The predictive accuracy of the score was greater than the other four commonly used staging systems for HCC.

Conclusion: The EHBH-MVI scoring system was more accurate in predicting prognosis in patients with HCC with MVI after R0 LR than the other four commonly used staging systems. The score can be used to supplement these systems.

Implications For Practice: Microvascular invasion (MVI) is a major determinant of survival outcomes after curative liver resection for patients with hepatocellular carcinoma (HCC). Currently, there is no scoring system aiming to predict prognosis of patients with HCC and MVI after R0 liver resection (LR). Most of the widely used staging systems for HCC do not use MVI as an independent risk factor, and they cannot be used to predict the prognosis of patients with HCC and MVI after surgery. In this study, a new Eastern Hepatobiliary Surgery Hospital (EHBH) MVI scoring system was established to predict prognosis of patients with HCC and MVI after R0 LR. Based on the results of this study, postoperative adjuvant therapy may be recommended for patients with HCC and MVI with an EHBH-MVI score >4. This score can be used to supplement the currently used HCC classifications to predict postoperative survival outcomes in patients with HCC and MVI.
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http://dx.doi.org/10.1634/theoncologist.2018-0868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6975940PMC
December 2019

Long-Term Survival Outcomes After Liver Resection for Binodular Hepatocellular Carcinoma: A Multicenter Cohort Study.

Oncologist 2019 08 24;24(8):e730-e739. Epub 2019 May 24.

The 1st Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People's Republic of China

Background: The long-term prognosis after liver resection for multinodular (≥3 nodules) hepatocellular carcinoma (HCC) is generally considered to be unfavorable. However, the role of liver resection for binodular HCC is less investigated.

Subjects, Materials, And Methods: From a multicenter database, consecutive patients who underwent curative-intent liver resection for binodular HCC and without macrovascular invasion between 2003 and 2015 were retrospectively reviewed. Patients' clinical variables as well as perioperative and long-term survival outcomes were analyzed. Univariable and multivariable analyses were performed to identify the risk factors associated with overall survival (OS) and recurrence-free survival (RFS) after curative resection.

Results: Of 263 enrolled patients, the perioperative 30-day mortality and morbidity rates were 1.5% and 28.5%. The 1-, 3-, and 5-year OS and RFS rates were 81.5%, 52.4%, and 39.1% and 57.1%, 35.8%, and 26.6%, respectively. Multivariable Cox-regression analyses identified preoperative alpha-fetoprotein level >400 μg/L, tumor size with a sum of two nodules >8 cm, tumor size ratio of large/small nodule >1.5 (asymmetrical proportion), unilateral hemiliver distribution of two nodules, distance of ≤3 cm between two nodules, and microvascular invasion in any nodule as independent risk factors associated with decreased OS and RFS.

Conclusion: Liver resection was safe and feasible in patients with binodular HCC, with acceptable perioperative and long-term outcomes. Sum of two tumor sizes, size ratio and distribution, and distance between two nodules were independent risk factors associated with long-term survival outcomes after surgery. These results may guide clinicians to make individualized surgical decisions and estimate long-term prognosis for these patients.

Implications For Practice: Liver resection was safe and feasible in patients with binodular hepatocellular carcinoma, with acceptable perioperative and long-term outcomes. The sum of two tumor sizes, the size ratio and distribution of the two nodules, and the distance between two nodules were independent risk factors associated with long-term overall survival and recurrence-free survival after liver resection. The results of this study may guide clinicians to make individualized surgical decisions, estimate long-term prognosis, and plan recurrence surveillance and adjuvant therapy for these patients.
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http://dx.doi.org/10.1634/theoncologist.2018-0898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693721PMC
August 2019

Association of family history with long-term prognosis in patients undergoing liver resection of HBV-related hepatocellular carcinoma.

Hepatobiliary Surg Nutr 2019 Apr;8(2):88-100

Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.

Background: Family history is a risk factor for the development of hepatocellular carcinoma (HCC). The aim of the current study was to investigate the association between family history of HCC and long-term oncologic prognosis among patients undergoing curative liver resection for hepatitis B virus (HBV)-related HCC.

Methods: Patients who underwent curative liver resection of HBV-related HCC between 2003 and 2013 were consecutively enrolled. Family history was defined as a self-reported history of HCC in a first-degree relative. Propensity score matching (PSM) and multivariable Cox-regression analyses were performed to compare overall survival (OS) and recurrence-free survival (RFS) among patients with and without a family history.

Results: Among 1,112 patients, 183 (16.5%) patients had a family history of HCC. Using PSM, 179 pairs of patients with and without a family history were created that had no differences in the baseline characteristics and operative variables. On matched analysis, family history was associated with decreased OS and RFS after curative-intent resection of HBV-related HCC in the propensity matching cohort (P=0.042 and 0.006, respectively). On multivariable Cox-regression analyses, a family history of HCC was associated with decreased OS (HR: 1.574; 95% CI: 1.171-2.116; P=0.003) and RFS (HR: 1.534; 95% CI: 1.176-2.002; P=0.002) after adjusting for other prognostic risk factors.

Conclusions: Family history was associated with decreased OS and RFS rates among patients undergoing curative liver resection of HBV-related HCC.
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http://dx.doi.org/10.21037/hbsn.2018.11.20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503234PMC
April 2019

Overexpression of MTHFD1 in hepatocellular carcinoma predicts poorer survival and recurrence.

Future Oncol 2019 May 18;15(15):1771-1780. Epub 2019 Apr 18.

Department of Pathology, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, PR China.

MTHFD1 was the enzyme providing one-carbon derivatives of tetrahydrofolate. We sought to investigate the impact of MTHFD1 on hepatocellular carcinoma (HCC). Bioinformatic analysis, western blot and immunohistochemistry were conducted to detect MTHFD1 expression in HCC. The relationships between MTHFD1 and prognosis of 172 HCCs were analyzed by Kaplan-Meier method and Cox proportional hazards model. High MTHFD1 expression in HCC represented poor prognosis (overall survival p = 0.025; time to recurrence p = 0.044). Combining MTHFD1 with serum AFP, survival analysis demonstrated the prognosis of the MTHFD1 low expression and AFP ≤20 ng/ml group was better than that of the MTHFD1 high expression or AFP >20 ng/ml group and the MTHFD1 high expression and AFP >20 ng/ml group (overall survival p < 0.0001; time to recurrence p < 0.0001). High MTHFD1 expression in HCC indicated poorer prognosis. Combining MTHFD1 with serum AFP improved the accuracy of prognostic prediction.
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http://dx.doi.org/10.2217/fon-2018-0606DOI Listing
May 2019

A nomogram to predict early postoperative recurrence of hepatocellular carcinoma with portal vein tumour thrombus after R0 liver resection: A large-scale, multicenter study.

Eur J Surg Oncol 2019 Sep 3;45(9):1644-1651. Epub 2019 Apr 3.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University Shanghai, China. Electronic address:

Background: Portal vein tumour thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first-order branch or above of the main portal vein (MPV) could benefit from R0 liver resection (LR). A nomogram is needed to predict early postoperative recurrence (ER) in HCC patients with PVTT and to guide selection of these patients for adjuvant therapy to reduce postoperative recurrence risks.

Methods: HCC patients with PVTT limited to a first-order branch or above of the MPV after R0 LR as an initial therapy were included. A nomogram using data from a retrospective training cohort was developed with the Cox regression model. The model was tested in a prospective internal validation cohort and three external validation cohorts.

Results: Of 979 patients, 657 developed postoperative ER (67.1%). ER occurred in 165 of 264 patients (62.5%) in the training cohort, 146 of 218 patients (70.0%) in the internal validation cohort, and 204 of 284 patients (71.8%), 77 of 113 patients (68.1%), and 65 of 100 patients (65%) in the three external validation cohorts, respectively. The nomogram included the following variables: hepatitis B surface antigen (HBsAg), PVTT, HBV DNA, satellite nodules, α-fetoprotein, and tumour diameter. The ROC were 0.836, 0.763, 0.802, 0.837, and 0.846 in predicting ER in the five respective cohorts.

Conclusion: A nomogram was developed and validated to predict postoperative ER in patients with HCC with PVTT after R0 LR. This nomogram could select appropriate patients with high ER risks for postoperative adjuvant therapy.
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http://dx.doi.org/10.1016/j.ejso.2019.03.043DOI Listing
September 2019

Postoperative Adjuvant Transarterial Chemoembolization Improves Outcomes of Hepatocellular Carcinoma Associated with Hepatic Vein Invasion: A Propensity Score Matching Analysis.

Ann Surg Oncol 2019 May 14;26(5):1465-1473. Epub 2019 Feb 14.

Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.

Background: Vascular invasion is a major determinant of survival outcomes after curative resection for hepatocellular carcinoma (HCC) patients. This study was designed to investigate the efficacy of postoperative adjuvant transarterial chemoembolization (PA-TACE) in patients with HCC with hepatic vein tumor thrombus (HVTT).

Methods: Data from patients who underwent LR for HCC with HVTT at the Eastern Hepatobiliary Surgery Hospital were retrospectively analyzed. The survival outcomes for patients who underwent PA-TACE after LR were compared with those who underwent LR alone. Propensity score matching (PSM) analysis was performed to match patients in a ratio of 1:1.

Results: All included 319 patients who underwent LR for HCC with HVTT, 134 underwent LR alone (the LR group), and 185 patients underwent in adjuvant TACE (the PA-TACE group). PSM matched 107 patients in two groups. The overall survival (OS) and recurrence-free survival (RFS) were significantly better for patients in the PA-TACE group than the LR group (for OS: before PSM, P < 0.001; after PSM, P = 0.004; for RFS: before PSM, P < 0.001; after PSM, P = 0.013), respectively. On subgroup analysis, equivalent acceptable results were obtained in patients with peripheral HVTT (pHVTT) and major HVTT (mHVTT). However, PA-TACE resulted in no survival benefits for patients when the HVTT had extended to the inferior vena cava (IVCTT).

Conclusions: PA-TACE was associated with significantly better survival outcomes than LR alone for patients with HCC and HVTT (pHVTT and mHVTT). There was no survival benefits in patients whose HVTT had extended to form IVCTT.
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http://dx.doi.org/10.1245/s10434-019-07223-zDOI Listing
May 2019