Showing papers by "Feng Shen published in 2021"

Number and Station of Lymph Node Metastasis After Curative-intent Resection of Intrahepatic Cholangiocarcinoma Impact Prognosis.

Abstract: OBJECTIVES To determine the prognostic implication of the number and station of LNM, and the minimal number of LNs needed for evaluation to accurately stage patients with intrahepatic cholangiocarcinoma (ICC). BACKGROUND Impact of the number and station of LNM on long-term survival, and the minimal number of LNs needed for accurate staging of ICC patients remain poorly defined. METHODS Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide. External validation was performed using the SEER registry. Primary outcomes included overall (OS), disease-specific, and recurrence-free survival. RESULTS Among 603 patients who underwent curative-intent resection, median and 5-year OS were 30.6 months and 30.4%. Patients with 1 or 2 LNM had comparable worse OS versus patients with no nodal disease (median OS, 1 LNM 18.0, 2 LNM 20.0 vs no LNM 45.0 months, both P < 0.001), yet better OS versus patients with 3 or more LNM (median OS, 1-2 LNM 19.8 vs ≥3 LNM 16.0 months, P < 0.01). On multivariable analysis, a proposed new nodal staging with N1 (1-2 LNM) (Ref. N0, HR 2.40, P < 0.001) and N2 (≥3 LNM) [Ref. N0, hazard ratio (HR) 3.85, P < 0.001] categories were independently associated with incrementally worse OS. Patients with no nodal metastasis, 1-2 LNM and ≥3 LNM also had an increasingly worse disease-specific survival, and recurrence-free survival (both P < 0.05). Total number of LNs examined ≥6 had the greatest discriminatory power relative to OS among patients with 1-2 LNM, and patients with ≥3 LNM in both the multi-institutional (area under the curve 0.780) and SEER database (area under the curve 0.820) (n = 1036). Among patients who underwent an adequate regional lymphadenectomy (total number of LNs examined ≥6), LNM beyond the HDL was associated with worse OS versus LNM within the HDL only (median OS, 14.0 vs 24.0 months, HR 2.41, P = 0.003). CONCLUSION Standard lymphadenectomy of at least 6 LNs is strongly recommended and should include examination beyond station 12 to have the greatest chance of accurate staging. The proposed new nodal staging of N0, N1, and N2 should be considered to stratify outcomes among patients after curative-intent resection of ICC.

Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy?

Abstract: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally. Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14–1.71; high TB: HR = 1.89, 95% CI 1.46–2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33–1.96; high TB: HR = 2.03, 95% CI 1.56–2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02). Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.

Nanotechnology for Hepatocellular Carcinoma: From Surveillance, Diagnosis to Management.

Abstract: Hepatocellular carcinoma (HCC) remains the fourth leading cause of cancer-related death worldwide. However, the clinical diagnosis and treatment modalities are still relatively limited, which urgently require the development of new effective technologies. Recently, nanotechnology has gained extensive attention in HCC surveillance, imaging and pathological diagnosis, and therapeutic strategies. Typically, nanomedicines have been focused on early HCC diagnosis and precise treatment of advanced HCC, which has developed and improved a variety of new technologies and agents for future clinical practice. Furthermore, strategies of facilitating drug release and delivery in current treatment processes such as ablation, systematic therapy, transcatheter arterial chemoembolization, molecular targeted therapy, and immune-modulating therapy have also been studied widely. This review summarizes the recent advances in this area according to current clinical HCC guidelines: 1) Nanoparticle-based HCC surveillance; 2) Nanotechnology for HCC diagnosis; 3) Therapeutic advances for HCC Management; 4) Limitations of applications in nanotechnology for HCC; 5) Conclusions and perspectives. Although there are still many limitations and difficulties to overcome, the investigations of nanomedicines are believed to show potential applications in clinical practice.

The Landscape of Cell-Free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

Abstract: Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful noninvasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. Patients with HCC (n = 481) and liver cirrhosis (LC; n = 517) were recruited in the study. Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was first generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR > 1) was identified as a potential HCC-related mutational hot zone. Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of noninvasive detection of virus insertion/mutation.

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

Abstract: Background: 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. Methods: In this work, HCC-derived extracellular vesicles (EVs) were applied as surface nanocarrier for sequential nanocatalysts GOD-ESIONs@EVs (GE@EVs) 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. Results: Through glucose consumption as catalyzed by the loaded glucose oxidase (GOD) to overproduce hydrogen peroxide (H2O2), 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 GE@EVs into HCC, achieving highly efficient tumor suppression both in vitro and in vivo. 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. Conclusion: This application of surface-engineering EVs not only proves the high-performance catalytic therapeutic modality of GE@EVs for HCC, but also broadens the versatile bio-applications of EVs.

Association between preoperative prealbumin level and postoperative mortality and morbidity after hepatic resection for hepatocellular carcinoma: A multicenter study from a HBV-endemic area.

Abstract: Background Prealbumin is a more sensitive serum biomarker in reflecting liver function and nutritional status than albumin, because of its shorter half-life and its characteristics that could hardly be affected by supplemental venous infusion of albumin or blood transfusion. This study aimed to identify whether preoperative prealbumin level was associated with postoperative mortality and morbidity after hepatic resection for patients with hepatocellular carcinoma (HCC). Methods From a Chinese multicenter database, patients who underwent hepatic resection for HCC were divided into the low and normal prealbumin groups by using 17 mg/dL as the cut-off level for serum prealbumin taken within a week before surgery. Using univariable and multivariable logistic regression analyses, independent predictors associated with postoperative 30-day and 90-day mortality, 30-day overall and major morbidity, and postoperative hepatic insufficiency were identified. Results Among 1356 patients, 409 (30.2%) had a low preoperative prealbumin level. Postoperative 30-day and 90-day mortality, and 30-day overall and major morbidity in the low prealbumin group were significantly higher than the normal prealbumin group (2.9% vs. 0.5%, 5.1% vs. 1.5%, 35.7% vs. 18.4%, and 14.4% vs. 6.5%, respectively, all P Conclusions Preoperative prealbumin level could be used to predict postoperative morbidity and mortality for patients treated with hepatic resection for HCC.

Development and validation of a novel online calculator for estimating survival benefit of adjuvant transcatheter arterial chemoembolization in patients undergoing surgery for hepatocellular carcinoma.

Abstract: BACKGROUND AND AIMS Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. METHODS From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. RESULTS A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child-Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. CONCLUSIONS Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Abstract: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide. The prognosis of patients with HCC remains poor largely due to the late diagnosis and lack of effective treatments. Despite being widely used, alpha-fetoprotein serology and ultrasonography have limited diagnostic performance for early-stage HCC. The emergence of omics strategies has contributed to significant advances in the development of non-invasive biomarkers for the early diagnosis of HCC including proteins, metabolites, circulating tumor deoxyribonucleic acid, and circulating non-coding ribonucleic acid. Early diagnosis is beneficial to patients as it increases the proportion who can be treated with curative treatment, thus prolonging survival outcomes. Currently, multiple clinical trials involving locoregional, systemic therapies, and combinations of these modalities are changing therapeutic strategies for different stage HCC. Success in several preclinical trials that involve immunotherapeutic innovations has created the potential to complement and enforce other treatment strategies in the future. This review summarizes the most recent advances in non-invasive early molecular detection, current therapy strategies, and potential immunotherapeutic innovations of HCC.

Postoperative adjuvant transarterial chemoembolization for intrahepatic cholangiocarcinoma patients with microvascular invasion: a propensity score analysis

Abstract: Background Microvascular invasion (MVI) is an independent risk factor associated with tumor recurrence and poor survival in patients with intrahepatic cholangiocarcinoma (ICC) after partial hepatectomy (PH). The potential impact of adjuvant TACE on the prognosis of patients with ICC involving MVI (ICC-MVI) remains uncertain. Our aim was to investigate the effectiveness of postoperative adjuvant transarterial chemoembolization (TACE) on ICC involving MVI. Methods Multicentric data consisted of 223 patients who underwent curative-intent PH for ICC-MVI from 2002-2015 were retrospectively analyzed. The impact of adjuvant TACE was evaluated using inverse probability of treatment weighting (IPTW) and propensity-score matched (PSM) analyses. Results No association between the TACE and the overall survival (OS) and recurrence rates was observed among the overall ICC-MVI patients. However, subgroup analyses revealed that adjuvant TACE favored OS (HR, 0.62; 95% CI, 0.39-0.99; P=0.047) and time to recurrence (TTR) (HR, 0.59; 95% CI, 0.36-0.97; P=0.037) among patients with elevated CA19-9 and those without lymphadenectomy (HR, 0.53; 95% CI, 0.30-0.93; P=0.027 for OS, and HR, 0.49; 95% CI, 0.28-0.87; P=0.015 for TTR, respectively). In the CA19-9 ≥39 U/L subgroup and Nx subgroup, adjuvant TACE was associated with higher 1-, 3-, and 5-year OS rates (P=0.033 and P=0.034, respectively) and lower corresponding recurrence rates (P=0.024 and P=0.023, respectively). Conclusions Among the ICC-MVI patients undergoing curative-intent PH, only those have elevated CA19-9 or who did not undergo lymphadenectomy might be suitable for adjuvant TACE.

Association of Postoperative Biomarker Response with Recurrence and Survival in Patients with Hepatocellular Carcinoma and High Alpha-Fetoprotein Expressions (>400 ng/ml).

Abstract: Background High alpha-fetoprotein (AFP) expressions (>400 ng/mL) are associated with poor oncological characteristics for hepatocellular carcinoma (HCC). However, prognosis after liver resection for high-AFP HCC is poorly studied. To investigate long-term recurrence and survival after hepatectomy for high-AFP HCC, and to identify the predictive value of postoperative incomplete biomarker response (IBR) on overall survival (OS) and recurrence-free survival (RFS). Methods Patients undergoing curative resection for high-AFP HCC were analyzed. According to the decline magnitude of serum AFP as measured at first follow-up (4~6 weeks after surgery), all patients were divided into the complete biomarker response (CBR) and IBR groups. Characteristics, recurrence, and survival rates were compared. Univariate and Multivariate Cox-regression analyses were performed to identify independent predictors associated with poorer OS and RFS after liver resection for high-AFP HCC. Results Among 549 patients, the overall and early recurrence rates in patients with IBR were significantly higher than patients with CBR (97.8%vs.56.4%, and 92.5%vs.33.3%, both P<0.001). On multivariate analysis, postoperative IBR was the strongest risk factor with the highest hazard ratio in predicting poor OS (HR 2.97; 95% CI 2.49~3.45; P<0.001) and RFS (HR 4.29; 95% CI 3.31~5.55; P<0.001). Conclusion Postoperative biomarker response of serum AFP can be used in predicting recurrence and survival for high-AFP HCC patients. Once postoperative IBR was identified at first follow-up, subsequent enhanced recurrence surveillance and available treatments against recurrence should actively be considered.

Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma.

Abstract: Background To improve the prognostic accuracy of the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC) with establishment and validation of a modified TNM (mTNM) staging system. Methods Data on patients who underwent curative-intent resection for ICC was collected from 15 high-volume centers worldwide (n = 643). An external validation dataset was obtained from the SEER registry (n = 797). The mTNM staging system was proposed by redefining T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1–2 LNM) and N2 (≥3 LNM). Results The 8th AJCC TNM staging system failed to stratify overall survival (OS) of stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV among all patients from the two databases, as well as stage I versus II, and stage III versus III among patients who had ≥6 LNs examined. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (Median OS, stage I 69.8 vs. II 37.1 vs. III 18.9 vs. IV 16.4 months, all p Conclusion The modified TNM staging system for ICC using the new T and N definitions provided an improved means to stratify patients relative to long-term OS versus the 8th AJCC staging.

Preoperative Estimated Risk of Microvascular Invasion is Associated with Prognostic Differences Following Liver Resection Versus Radiofrequency Ablation for Early Hepatitis B Virus-Related Hepatocellular Carcinoma.

Abstract: The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma (HCC) based on preoperative predicted microvascular invasion (MVI) risk. Data on consecutive patients who underwent LR (n = 1344) or PRFA (n = 853) for hepatitis B virus-related HCC within the Milan criteria (MC) were analyzed. A preoperative nomogram was used to estimate MVI risk. Overall survival (OS), time to recurrence, and patterns of recurrence were compared using propensity score matching. The concordance indices of the nomogram to predict MVI were 0.813 and 0.781 among LR patients with HCC within the MC or ≤ 3 cm, respectively. LR and PRFA resulted in similar 5-year recurrence and OS for patients with nomogram-predicted low-risk of MVI. LR provided better 5-year recurrence and OS versus PRFA for patients with high-risk of MVI (71.6% vs. 80.7%, p = 0.013; 47.9% vs. 34.0%, p = 0.002, for HCC within the MC; 62.3% vs. 78.8%, p = 0.020; 63.6% vs. 38.3%, p = 0.015, for HCC ≤ 3 cm). Among high-risk patients, LR was associated with lower recurrence and improved OS compared with PRFA, on multivariate analysis [hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.63–0.97, and HR 0.68, 95% CI 0.52–0.88, for HCC within the MC; HR 0.51, 95% CI 0.32–0.81, and HR 0.47, 95% CI 0.26–0.84, for HCC ≤ 3 cm], and resulted in less early and local recurrence than PRFA (42.4% vs. 54.8%, p = 0.007, and 31.2% vs. 46.1%, p = 0.007, for HCC within the MC; 27.9% vs. 50.8%, p = 0.016, and 15.6% vs. 39.5%, p = 0.046, for HCC ≤ 3 cm). LR was oncologically superior over PRFA for early HCC patients with predicted high-risk of MVI. LR was associated with better local disease control than PRFA in these patients.

Biomarkers for hepatocellular carcinoma based on body fluids and feces.

Abstract: Novel non-/minimally-invasive and effective approaches are urgently needed to supplement and improve current strategies for diagnosis and management of hepatocellular carcinoma (HCC). Overwhelming evidence from published studies on HCC has documented that multiple molecular biomarkers detected in body fluids and feces can be utilized in early-diagnosis, predicting responses to specific therapies, evaluating prognosis before or after therapy, as well as serving as novel therapeutic targets. Detection and analysis of proteins, metabolites, circulating nucleic acids, circulating tumor cells, and extracellular vesicles in body fluids (e.g., blood and urine) and gut microbiota (e.g., in feces) have excellent capabilities to improve different aspects of management of HCC. Numerous studies have been devoted in identifying more promising candidate biomarkers and therapeutic targets for diagnosis, treatment, and monitoring responses of HCC to conventional therapies, most of which may improve diagnosis and management of HCC in the future. This review aimed to summarize recent advances in utilizing these biomarkers in HCC and discuss their clinical significance.

A combined Cox and logistic model provides accurate predictive performance in estimation of time-dependent probabilities for recurrence of intrahepatic cholangiocarcinoma after resection

Abstract: Background Intrahepatic cholangiocarcinoma has heterogeneous outcomes after resection. There remains a need for broadly applicable recurrence-specific tool offering precise evaluation on curativeness of resection. Methods A four hospital-based clinical cohort involving 1,655 patients with intrahepatic cholangiocarcinoma who received surgical resection were studied. Cox and logistic models were networked into one system containing risk categories with distinctive probabilities of recurrence. Prediction of time-to-recurrence was performed by formulizing time-dependent risk probabilities. The model was validated in three clinical cohorts (n=332). Results From the training cohort, 10 and 11 covariates, including diabetes, cholelithiasis, albumin, platelet count, alpha fetoprotein, carbohydrate antigen 19-9, carcinoembryonic antigen, hepatitis B virus infection, tumor size and number, resection type, and lymph node metastasis, from Cox and logistic models were identified significant for recurrence-free survival (RFS). The combined Cox & logistic ranking system (CCLRS)-adjusted time-dependent probabilities were categorized into seven ranks (5-yr RFS for lowest and highest ranks were 75% vs. 0%; hazard ratio 18.5, 95% CI: 14.7-24.9, P<0.0001). The CCLRS was validated with a minimum area under curve value of 0.8086. Prediction of time-to-recurrence was validated to be excellent (Pearson r, 0.8204; P<0.0001). Conclusions The CCLRS allows precise estimation on risk of recurrence for intrahepatic cholangiocarcinoma after resection. It could be applicative when estimating time-dependent disease status and stratifying individuals who sole resection of the tumor would not be curative.

Prognostic factors of resectable perihilar cholangiocarcinoma: a systematic review and meta-analysis of high-quality studies:

Abstract: Data on prognostic factors associated with outcome following resection of perihilar cholangiocarcinoma vary. We sought to define and characterize current available evidence on prognostic factors as...

Long-Term Surgical Outcomes of Liver Resection for Hepatocellular Carcinoma in Patients With HBV and HCV Co-Infection: A Multicenter Observational Study.

Abstract: Background Hepatocellular carcinoma (HCC) is one of the most serious consequences of chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. This study sought to investigate long-term outcomes after liver resection for HCC among patients with HBV/HCV co-infection (HBV/HCV-HCC) compared with patients with HBV infection (HBV-HCC). Methods Patients who underwent curative-intent liver resection for HCC were identified from a multicenter Chinese database. Using propensity score matching (PSM), patients with HBV/HCV-HCC were matched one-to-one to patients with HBV-HCC. Overall survival (OS) and recurrence-free survival (RFS) were compared between the two groups before and after PSM. Results Among 2,467 patients identified, 93 (3.8%) and 2,374 (96.2%) patients had HBV/HCV-HCC and HBV-HCC, respectively. Compared with patients with HBV-HCC, patients with HBV/HCV-HCC were older, have poorer liver-related characteristics but better tumor-related characteristics. PSM created 88 pairs of patients with comparable liver- and tumor-related characteristics (all P > 0.2). In the PSM cohort, the 3- and 5-year RFS rates in patients with HBV/HCV-HCC were 48.3% and 38.9%, which were significantly poorer than patients with HBV-HCC (61.8% and 49.2%, P = 0.037). Meanwhile, the 3- and 5-year OS rates in patients with HBV/HCV-HCC were also poorer than patients with HBV-HCC (65.4% and 51.1% vs. 73.7% and 63.0%), with a difference close to be significant between them (P = 0.081). Conclusion Comparing to patients with HBV-HCC, liver resection resulted in relatively poorer long-term surgical outcomes in patients with HBV/HCV-HCC.

Distinct Impacts of Pre-Operative Antiviral Treatment on Post-Operative Outcomes of HBV-related Hepatocellular Carcinoma: A Landmark Analysis.

Abstract: Background: The effect of anti-viral treatment (AVT) initiated before surgery (pre-operative AVT) on HBV-related hepatocellular carcinoma (HCC) has been controversial. This study aimed to elucidate the prognostic significance of pre-operative AVT for HCC patients who received hepatectomy. Materials and Methods: A large-scale retrospective study was conducted based on a cohort consisting of 1937 HBV-related HCC patients who underwent R0 liver resection between January 2011 and December 2012. Propensity score matching (PSM) method was adopted to balance covariates and landmark survival analyses were performed to visualize effects in different phases after surgery. Results: After PSM, a total of matched 744 patients (372 in each group) were recruited. The patients in the pre-operative AVT group had lower HBV-DNA loading levels and better recurrence-free survival (RFS) than those in the non-AVT group. The 1, 3, 5-year RFS rates of two groups were 67.3%, 49.0%, and 43.1% vs. 66.7%, 41.1% and 18.5%, respectively (P 5cm), esophageal and gastric varices, lymph node metastasis were independent risk factors of RFS, and larger tumor (>5cm) and ascites were independent risk factors of OS. Conclusions: Pre-operative AVT could significantly improve the RFS, and could not improve short-term OS (< 36 months) but could better long-term survival of the patients with HBV-HCC after surgery.

Nomogram for predicting pathologic complete response after transarterial chemoembolization in patients with hepatocellular carcinoma.

Abstract: Background The pathologic responses to transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) are heterogeneous and result in disparate outcomes. The study aimed to establish and validate an effective nomogram for predicting pathologic complete response (PCR) after TACE. Methods We analyzed the clinicopathologic characteristics of HCC patients undergoing hepatectomy following TACE. Variables with statistical significance in a multivariate logistic regression analysis were incorporated in the nomogram. Results We detected PCR in 64 (50.4%) patients in the training cohort and 18 (37.5%) patients in the validation cohort. Univariable and multivariable logistic regression revealed that hepatitis B virus (HBV) DNA load (P=0.031), α-fetoprotein (AFP, P=0.040), maximum tumor diameter (P=0.003), preoperative TACE session (P=0.026), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) complete response (P=0.030) were identified as significant predictors of PCR. Incorporating these 5 factors, a nomogram was developed which attained concordance indexes of 0.80 [95% confidence interval (CI): 0.72-0.87] and 0.82 (95% CI: 0.68-0.95) for predicting PCR in the training and validation cohorts, respectively. Conclusions The easy-to-use nomogram achieved a good post-TACE prediction of PCR in HCC patients. Using the model, patients who would benefit most from TACE could be identified, and the subsequent appropriate procedures could be guided accordingly.

Postoperative morbidity adversely impacts long-term oncologic prognosis following hepatectomy for hepatocellular carcinoma: A multicenter observational study.

Abstract: Background & aims Postoperative morbidity following hepatectomy for hepatocellular carcinoma (HCC) is common and its impact on long-term oncological outcome remains unclear. This study aimed to investigate if postoperative morbidity impacts long-term survival and recurrence following hepatectomy for HCC. Methods The data from a multicenter Chinese database of curative-intent hepatectomy for HCC were analyzed, and independent risks of postoperative 30-day morbidity were identified. After excluding patients with postoperative early deaths (≤90 days), early (≤2 years) and late (>2 years) recurrence rates, overall survival (OS), and time-to-recurrence (TTR) were compared between patients with and without postoperative morbidity. Results Among 2,161 patients eligible for the study, 758 (35.1%) had postoperative 30-day morbidity. Multivariable logistic regression analysis showed that diabetes mellitus, obesity, Child-Pugh grade B, cirrhosis, and intraoperative blood transfusion were independent risks of postoperative morbidity. The rates of early and late recurrence among patients with postoperative morbidity were higher than those without (50.7% vs. 38.8%, P Conclusion This large multicenter study provides strong evidence that postoperative morbidity adversely impacts long-term oncologic prognosis after hepatectomy for HCC. The prevention and management of postoperative morbidity may be oncologically important.

Long-term oncologic outcomes of liver resection for hepatocellular carcinoma in adolescents and young adults: A multicenter study from a hepatitis B virus-endemic area.

Abstract: Background Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection. Methods From a Chinese multicenter database, patients were categorized as AYA (aged 13–39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR. Results Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age ( Conclusions Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

Chinese expert recommendations on management of hepatocellular carcinoma during COVID-19 pandemic: a nationwide multicenter survey.

Abstract: Background This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic. Methods A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic. Results 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the “face-to-face” visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC. Discussion During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery.

Mesoporous Silica Nanoparticles for Potential Immunotherapy of Hepatocellular Carcinoma.

Abstract: Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related death worldwide, which lacks effective inhibition of progression and metastasis in the advanced clinical stage. Mesoporous silica nanoparticle (MSN)-based cytotoxic or immunoregulatory drug-loading strategies have attracted widespread attention in the recent years. As a representative of mesoporous biomaterials, MSNs have good biological characteristics and immune activation potential and can cooperate with adjuvants against HCC. This review summarizes the possible future development of the field from the perspective of tumor immunity and aims to stimulate the exploration of the immune mechanism of MSN-based therapy. Through this point of view, we hope to develop new clinical immune drugs that can be applied to HCC clinical management in the future.

The value of lymphadenectomy in surgical resection of perihilar cholangiocarcinoma: a systematic review and meta-analysis.

Abstract: Surgical resection is the only potentially curative treatment for patients with resectable perihilar cholangiocarcinoma (PHC). There is still no consensus on the value of lymphadenectomy despite evidence indicating lymph node (LN) status is an important prognostic indicator for postoperative long-term survival. We sought to perform a meta-analysis to summarize the current evidence on the value of lymphadenectomy among patients undergoing surgery for PHC. The PubMed (OvidSP), Embase and Cochrane Library were systematically searched for studies published before July 2020 that reported on lymphadenectomy at the time of surgery for PHC after curative surgery. 7748 patients from 28 studies were included in the meta-analysis. No survival benefit was identified with increased number of LN resected (all P > 0.05). Meanwhile, overall LN status was an important prognostic factor. Patients with lymph node metastasis had a pooled estimate hazard ratio of death that was over two-fold higher than patients without lymph node metastasis (HR 2.07, 95% CI 1.65–2.59, P < 0.001). The examination of 5 LNs on histology was associated with better staging of lymph node status and stratification of patients into positive or negative LN groups. While the extent of LN dissection was not associated with a survival benefit, examination of more than 5 LNs better staged patients into positive or negative LN groups with a lower risk of nodal understaging.

Development and validation of an individualized prediction calculator of postoperative mortality within 6 months after surgical resection for hepatocellular carcinoma: an international multicenter study

Abstract: Evidence-based decision-making is critical to optimize the benefits and mitigate futility associated with surgery for patients with malignancies. Untreated hepatocellular carcinoma (HCC) has a median survival of only 6 months. The objective was to develop and validate an individualized patient-specific tool to predict preoperatively the benefit of surgery to provide a survival benefit of at least 6 months following resection. Using an international multicenter database, patients who underwent curative-intent liver resection for HCC from 2008 to 2017 were identified. Using random assignment, two-thirds of patients were assigned to a training cohort with the remaining one-third assigned to the validation cohort. Independent predictors of postoperative death within 6 months after surgery for HCC were identified and used to construct a nomogram model with a corresponding online calculator. The predictive accuracy of the calculator was assessed using C-index and calibration curves. Independent factors associated with death within 6 months of surgery included age, Child–Pugh grading, portal hypertension, alpha-fetoprotein level, tumor rupture, tumor size, tumor number and gross vascular invasion. A nomogram that incorporated these factors demonstrated excellent calibration and good performance in both the training and validation cohorts (C-indexes: 0.802 and 0.798). The nomogram also performed better than four other commonly-used HCC staging systems (C-indexes: 0.800 vs. 0.542–0.748). An easy-to-use online prediction calculator was able to identify patients at highest risk of death within 6 months of surgery for HCC. The proposed online calculator may help guide surgical decision-making to avoid futile surgery for patients with HCC.