Liver resection versus liver transplantation for hepatocellular carcinoma within Milan criteria: a meta-analysis of 18,421 patients

BackgroundOutcomes after liver resection (LR) and liver transplantation (LT) for hepatocellular carcinoma (HCC) are heterogenous and may vary by region, over time periods and disease burden. We aimed to compare overall survival (OS) and disease-free survival (DFS) between LT versus LR for HCC within the Milan criteria.MethodsTwo authors independently searched Medline and Embase databases for studies comparing survival after LT and LR for patients with HCC meeting the Milan criteria. Meta-analyses and metaregression were conducted using random-effects models.ResultsWe screened 2,278 studies and included 35 studies with 18,421 patients. LR was associated with poorer OS [hazard ratio (HR) =1.44; 95% confidence interval (CI): 1.14–1.81; P<0.01] and DFS (HR =2.71; 95% CI: 2.23–3.28; P<0.01) compared to LT, with similar findings among intention-to-treat (ITT) studies. In uninodular disease, OS in LR was comparable to LT (P=0.13) but DFS remained poorer (HR =2.95; 95% CI: 2.30–3.79; P<0.01). By region, LR had poorer OS versus LT in North America and Europe (P≤0.01), but not Asia (P=0.25). LR had inferior survival versus LT in studies completed before 2010 (P=0.01), but not after 2010 (P=0.12). Cohorts that underwent enhanced surveillance had comparable OS after LT and LR (P=0.33), but cohorts undergoing usual surveillance had worse OS after LR (HR =1.95; 95% CI: 1.24–3.07; P<0.01).ConclusionsMortality after LR for HCC is nearly 50% higher compared to LT. Survival between LR and LT were similar in uninodular disease. The risk of recurrence after LR is threefold that of LT.     

Characteristics and outcomes of hepatocellular carcinoma patients with macrovascular invasion following surgical resection: a meta-analysis of 40 studies and 8,218 patients

BackgroundGuidelines recommend that hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) and/or hepatic vein tumor thrombosis (HVTT) should undergo systemic therapy. However, recent data suggest that surgical resection may be beneficial in selected cases, but outcomes are heterogenous. We aimed to estimate pooled overall survival (OS), recurrence free survival (RFS) and complication rates in HCC patients with macrovascular invasion (MVI) following surgical resection.MethodsIn this systematic review and meta-analysis, two investigators independently searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020, without language restrictions, for studies reporting outcomes of adult HCC patients with MVI who underwent liver resection with curative intent.ResultsWe screened 8,598 articles and included 40 studies involving 8,218 patients. Among all patients with MVI, the pooled median OS was 14.39 months [95% confidence interval (CI): 10.99–18.84], 1-year OS was 54.47% (95% CI: 46.12–62.58%) and 3-year OS was 23.20% (95% CI: 16.61–31.42%). Overall, 1- and 3-year RFS were 27.70% (95% CI: 21.00–35.57%) and 10.06% (95% CI: 6.62–15.01%), respectively. Among patients with PVTT, median OS was 20.41 months in those with segmental/2nd order involvement compared to 12.91 months if 1st order branch was involved and 6.41 months if the main trunk was involved. The pooled rate of major complications was 6.17% (95% CI: 3.53–10.56%).ConclusionsOverall median survival was 14.39 months for HCC patients with MVI following resection. Median survival was higher in PVTT with segmental/2nd order involvement at 20.41 versus 6.41 months if the main trunk was involved.     

Associating liver partition and portal vein ligation for staged hepatectomy versus sequential transarterial chemoembolization and portal vein embolization in staged hepatectomy for HBV-related hepatocellular carcinoma: a randomized comparative study

BackgroundBoth portal vein embolization (PVE) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) have merits and demerits when used in patients with unresectable liver cancers due to insufficient volumes in future liver remnant (FLR).MethodsThis study was a single-center, prospective randomized comparative study. Patients with the diagnosis of hepatitis B related hepatocellular carcinoma (HCC) were randomly assigned in a 1:1 ratio to the 2 groups. The primary endpoints were tumor resection and three-year overall survival (OS) rates.ResultsBetween November 2014 to June 2016, 76 patients with unresectable HBV-related HCC due to inadequate volume of FLR were randomly assigned to ALPPS groups (n=38) and TACE + PVE groups (n=38). Thirty-seven patients (97.4%) in the ALPPS group compared with 25 patients (65.8%) in the TACE + PVE group were able to undergo staged hepatectomy (risk ratio 1.48, 95% CI: 1.17–1.87, P<0.001). The three-year OS rate of the ALPPS group (65.8%) (95% CI: 50.7–80.9) was significantly better than the TACE + PVE group (42.1%) (95% CI: 26.4–57.8) (HR 0.50, 95% CI: 0.26–0.98, two-sided P=0.036). However, no significant difference in the OS rates between patients who underwent tumor resection in the 2 groups of patients was found (HR 0.80, 95% CI: 0.35–1.83, two-sided P=0.595). Major postoperative complications rates after the stage-2 hepatectomy were 54.1% in the ALPPS group and 20.0% in the TACE + PVE group (risk ratio 2.70, 95% CI: 1.17–6.25, P=0.007).ConclusionsALPPS resulted in significantly better intermediate-term OS outcomes, at the expenses of a significantly higher perioperative morbidity rate compared with TACE + PVE in patients who had initially unresectable HBV-related HCC.     

A Propensity-Matched Analysis of Outcomes of Patients with Clinical Stage I Non–Small Cell Lung Cancer Treated surgically or with stereotactic radiotherapy: A Meta-Analysis

Objective: The aim of this study was to compare the efficacy between SBRT and surgery based on the Propensity-Matched Analysis. Methods: Publications on comparison SBRT and Surgery for early stage non- small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Propensity score matching was used to achieve comparable treatment hazard ratios of the overall survival (OS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), distant control survival (DC), disease-free survival (DFS), and progression-free survival (PFS) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. Result: Eleven studies met our inclusion criteria. The LC, L-R C, DC, DFS and PFS rates of patients with early-stage lung cancer who were treated with SBRT are equal to surgical results. While, patients with surgery achieved superior OS compared with SBRT. Conclusion: In this study we carried out a meta-analysis, which controls the acceptable level of the efficacy in the propensity score to match patients. The surgery had obvious OS advantages in this meta-analysis. However, these conclusions would be proven by further studies incorporating comorbidity data, and outcomes from randomized control study. The final decision for the optimal treatment of a patient with early-stage NSCLC can be substantiated by a personalized treatment model.     

Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients

BackgroundHepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.MethodsA total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27–78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.ResultsA total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0–28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A, and FGF19. SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III–IV and microvascular invasion was significantly higher in TP53 mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in TERT mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in CTNNB1 mutated patients (P<0.05). CTNNB1 mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of TP53 was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III–IV (P=0.008, OR =2.613). The mutation of TERT was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of CTNNB1 was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).ConclusionsThe most frequently mutated genes of HCC patients in China were TP53, TERT, and CTNNB1, which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III–IV grade in TP53 mutated patients and more patients with hepatic capsule invasion in TERT mutated patients, while in CTNNB1 mutated patients, there were more patients with Edmondson I–II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in CTNNB1 mutated patients than in wild type patients.     

A new staging system for hepatocellular carcinoma associated with portal vein tumor thrombus

BackgroundA new staging system for patients with hepatocellular carcinoma (HCC) associated with portal vein tumor thrombus (PVTT) was developed by incorporating the good points of the BCLC classification of HCC, and by improving on the currently existing classifications of HCC associated with PVTT.MethodsUnivariate and multivariate analysis with Wald χ² test were used to determinate the clinical prognostic factors for overall survival (OS) in patients with HCC and PVTT in the training cohort. Then the conditional inference trees analysis was applied to establish a new staging system.ResultsA training cohort of 2,179 patients from the Eastern Hepatobiliary Surgery Hospital and a validation cohort of 1,550 patients from four major liver centers in China were enrolled into establishing and validating a new staging system. The system was established by incorporating liver function, general health status, tumor resectability, extrahepatic metastasis and extent of PVTT. This staging system had a good discriminatory ability to separate patients into different stages and substages. The median OS for the two cohorts were 57.1 (37.2–76.9), 12.1 (11.0–13.2), 5.7 (5.1–6.2), 4.0 (3.3–4.6) and 2.5 (1.7–3.3) months for the stages 0 to IV, respectively (P<0.001) in the training cohort. The corresponding figures for the validation cohort were 6.4 (4.9–7.9), 2.8 (1.3–4.4), 10.8 (9.3–12.4), and 1.5 (1.3–1.7) months for the stages II to IV, respectively (P<0.001). The mean survival for stage 0 to 1 were 37.6 (35.9–39.2) and 30.4 (27.4–33.4), respectively (P<0.001).ConclusionsA new staging system was established which provided a good discriminatory ability to separate patients into different stages and substages after treatment. It can be used to supplement the other HCC staging systems.     

Extreme body mass index is associated with poor survival outcomes after radical cystectomy: a retrospective cohort study in a Chinese population

BackgroundBody mass index (BMI) has been evidenced to be a significant prognostic factor in multiple cancers. This retrospective study aimed to investigate the association between BMI and survival outcomes after radical cystectomy (RC) in patients with bladder cancer (BCa).MethodsClinical and pathological parameters of patients who were diagnosed with BCa and received RC between 2010 and 2018 were collected. The associations between BMI at surgery and clinicopathological features were examined. The prognostic value of BCa for overall survival (OS) and cancer-specific survival (CSS) was examined using the Kaplan-Meier method and Cox regression models.ResultsAmong the 217 patients enrolled in this study, 13 (6.0%), 121 (55.8%), 60 (27.6%), and 23 (10.6%) had a BMI value of <18.5 kg/m² (underweight), 18.5–23.9 kg/m² (normal), 24–27.9 kg/m² (overweight), and ≥28 kg/m² (obese), respectively. Underweight and obese patients tended to have poorer survival after RC than normal and overweight patients (P<0.05). Multivariable Cox regression revealed that extreme BMI was an independent predictor of both OS (BMI <18.5 vs. 18.5–27.9 kg/m², OR =2.675, 95% CI: 1.131–6.327, P=0.025; BMI ≥28 vs. 18.5–27.9 kg/m², OR =3.693, 95% CI: 1.589–8.583, P=0.002) and CSS (BMI <18.5 vs. 18.5–27.9 kg/m², OR =3.012, 95% CI: 1.180–7.687, P=0.021; BMI ≥28 vs. 18.5–27.9 kg/m², OR =3.801, 95% CI: 1.526–9.469, P=0.004), along with tumor stage and urinary diversion type.ConclusionsBeing underweight or obese is associated with a poor prognosis in patients with BCa undergoing RC. For patients who are preparing to undergo RC for BCa, controlling the BMI index through diet or exercise before surgery may contribute to the surgical curative effect and an improved prognosis.     

Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis

ABSTRACT

Objective: Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. Methods: Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. Result: A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. Conclusion: In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.     

Smoking status and pathological response to neoadjuvant chemotherapy among patients with bladder cancer: a pooled analysis

BackgroundSmoking status has been confirmed as an independent prognostic factor for bladder cancer. However, for patients who received neoadjuvant chemotherapy (NAC), the influence of smoking status on the pathological response and prognosis remains unclear. This pooled analysis aimed to investigate whether smoking status is an independent risk factor for pathological response, recurrence, and prognosis in patients with bladder cancer who undergo NAC.MethodsWe searched PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar for related studies published between 1990 and 2017. In total, 10 studies comprising 1,382 patients with muscle-invasive bladder cancer were included. The odds ratio (OR) and 95% confidence interval (CI) of complete pathological response, partial pathological response, overall survive (OS), recurrence, and cancer-specific mortality (CSM) were chosen as outcome measures. Analyses were performed using Review Manager (version 5.3, The Cochrane Collaboration, UK) and Stata statistical software (version 15, Stata Corp., USA).ResultsCompared to nonsmokers, smokers were less likely to have a complete pathologic response (OR =0.55, 95% CI: 0.35–0.87) and partial pathological response (OR =0.57, 95% CI: 0.37–0.88). However, we found no significant association between smoking status and overall survival (OR =0.71, 95% CI: 0.28–1.80), recurrence (OR =1.35, 95% CI: 0.97–1.88), and cancer-specific mortality (OR =0.90, 95% CI: 0.62–1.32).ConclusionsSmoking reduces both complete and partial pathological response rate to NAC in patients with bladder cancer. Thus, smoking status should be given more importance when developing treatment plans and evaluating efficacy, particularly of NAC, among bladder cancer patients.     

Prognostic effect of preoperative serum albumin to globulin ratio in patients treated with cytoreductive nephrectomy for metastatic renal cell carcinoma

BackgroundAccurate identification of ideal candidates for cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is an unmet need. We tested the association between preoperative value of systemic albumin to globulin ratio (AGR) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN.MethodsmRCC patients treated with CN were included. The overall population was therefore divided into two AGR groups using cut-off of 1.43 (low, <1.43 vs. high, ≥1.43). Univariable and multivariable Cox regression analyses tested the association between AGR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel’s concordance index (C-index). The clinical value of the AGR was evaluated with decision curve analysis (DCA).ResultsAmong 613 mRCC patients, 159 (26%) patients had an AGR <1.43. Median follow-up was 31 (IQR: 16–58) months. On univariable analysis, low preoperative serum AGR was significantly associated with both OS (HR: 1.55, 95% CI: 1.26–1.89, P<0.001) and CSS (HR: 1.55, 95% CI: 1.27–1.90, P<0.001). On multivariable analysis, AGR <1.43 was associated with worse OS (HR: 1.51, 95% CI: 1.23–1.85, P<0.001) and CSS (HR: 1.52, 95% CI: 1.24–1.86, P<0.001). The addition of AGR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index=0.640 vs. C-index=0.629). On DCA, the inclusion of AGR marginally improved the net benefit of the prognostic model. Low AGR remained independently associated with OS and CSS in the IMDC intermediate risk group (HR: 1.52, 95% CI: 1.16–1.99, P=0.002).ConclusionsIn our study, low AGR before CN was associated with worse OS and CSS, particularly in intermediate risk patients.     

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis

BackgroundTo study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients.MethodsBetween 2013 to 2015, consecutive HCC patients who underwent liver resection with “curative” intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM).ResultsOf 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60–90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082–0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561–0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004–11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095–1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.ConclusionsThis study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences     

ALP bouncing and LDH normalization in bone metastatic castration-resistant prostate cancer patients under therapy with Enzalutamide: an exploratory analysis

BackgroundIn bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.MethodsEighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.ResultsIn Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2–9.8] vs. 3 (2.3–3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1–8) vs. 2 (1.2–2.8) for LDH-normalization (P<0.01) and 8 (0–16.3) vs. 3 (1.9–4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7–22.3) vs. 12 (7.0–17.1) months for PSA (P=0.35), 17 (13.2–20.8) vs. 7 (5.8–8.2) for LDH-normalization (P<0.01) and 19 (7.9–30.1) vs. 12 (7.7–16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3–1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3–0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2–0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2–0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2–1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2–21.8) vs. 4 (0–8.6); P=0.01] and OS [20 (17.7–22.3) vs. 8 (0.3–15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1–0.7); P<0.01] and OS [HR: 0.3 (0.1–0.8); P=0.02].ConclusionsALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.     

Positive association between preoperative lymphocyte-to-monocyte ratio and risk of the status of positive surgical margins by prostate cancer: results in 497 consecutive patients treated only by radical prostatectomy

BackgroundPositive surgical margins (PSM) is one of the most important factors affecting the prognosis of prostate cancer (PCa) patients after radical prostatectomy (RP). Although some studies have found the preoperative systematic inflammation-based scores the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR) can predict the incidence and prognosis of PCa, few studies have explored the predictive value of preoperative systematic inflammation-based scores on the PSMs for PCa patients after RP.MethodsFrom June 2014 to September 2020 a total of 497 patients underwent RP at our institution. Blood samples from all patients were collected within one week before surgery. Preoperative clinical characteristics including age, body mass index (BMI), prostate-specific antigen (PSA), and biopsy Gleason sum (BGS) were assessed. Postoperatively pathological specimens were assessed for pathological Gleason sum (PGS), pathological stage, and margin status.ResultsIn the multivariable analysis including preoperative variables, PSA and LMR were the independent predictive factors for PSM (OR: 2.817; 95% CI, 1.836–4.320, P<0.001; OR: 1.124; 95% CI, 1.018–1.240, P=0.021. Considering pre-, intra-, and postoperative variables, BGS, perineural invasion, seminal vesicle invasion (SVI), pathologic Gleason sum (PGS) combined, were associated with increased risk of PSM in the univariable analysis (P<0.001 for all variables). However, in the multivariable analysis, perineural invasion (OR: 2.672; 95% CI, 1.649–4.330; P<0.001), PGS (OR: 2.52; 95% CI, 1.556–4.082; P<0.001) were independent predictive factors for the incidence of PSM. Finally, LMR was shown to be an independent predictive factor (OR: 0.881; 95% CI, 0.779–0.996; P=0.043) for apical PSMs, with increasing LMR predicting the lower incidence of apex location. And we also found that LMR was an independent factor that predicts multifocal positive margins (OR: 1.179; 95% CI, 1.023–1.358; P=0.023).ConclusionsPreoperative LMR could be used as an independent predictor to predict the incidence of PSMs after RP. And Considering pre-, intra-, and postoperative variables, we also found that preoperative LMR could predict the occurrence of apical and multifocal PSMs.     

Radiofrequency Ablation for Subcapsular Hepatocellular Carcinoma

Background: Limited data from recent studies suggested an increased risk of bleeding complications, needle-track seeding, and local recurrence after radiofrequency ablation (RFA) of subcapsular hepatocellular carcinoma (HCC).Methods: Between May 2001 and October 2002, 80 patients underwent RFA of 104 HCC nodules. Forty-eight patients had subcapsular HCC (group I), whereas the other 32 patients did not have subcapsular HCC (group II). RFA was performed via celiotomy, laparoscopy, or a percutaneous approach. Subcapsular HCCs were ablated by indirect puncture through nontumorous liver, and the needle track was thermocoagulated.Results: There were no significant differences between groups in treatment morbidity (14.6% vs. 15.6%; P = .898), mortality (2.1% vs. 0%; P = 1.000), complete ablation rate after a single session (89.4% vs. 96.9%; P = .392), local recurrence rate (4.3% vs. 12.5%; P = .216), recurrence-free survival (1 year: 60.9% vs. 49.2%; P = .258), or overall survival (1 year: 88.3% vs. 79.4%; P = .441). After a median follow-up of 13 months, no needle-track seeding or intraperitoneal metastasis was observed.Conclusions: This study shows that the results of RFA for subcapsular HCCs are comparable to those of RFA for nonsubcapsular HCCs. Subcapsular HCC should not be considered a contraindication for RFA treatment.     

Neoadjuvant radiotherapy for resectable hepatocellular carcinoma with portal vein tumor thrombus: a systematic review

BackgroundThe prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The clinical outcome of preoperative radiotherapy (RT) is still controversial. This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.MethodsComprehensive database searches were performed in PubMed, the Cochrane Library, EMBASE, and the Web of Science to retrieve studies published from the database creation to July 1, 2020. Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included. The characteristics of the included studies and patients were extracted, and the included data are presented as relative ratio (RR) estimates with 95% confidence intervals (CIs) for all outcomes. The RRs of each study were pooled using a fixed or random effects model with Review Manager (the Cochrane Collaboration, Oxford, UK) version 5.3. The response rate to RT and the overall survival (OS) rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.ResultsOne randomized and two non-randomized controlled trials with 302 patients were included. Most patients were classified as Child-Pugh A, and Type II and III PVTT were the most common types. After RT, 29 (22.8%) patients were evaluated as partial response (PR) and had a positive RT response, but nine (7.1%) had progressive disease (PD). Neoadjuvant RT followed by hepatectomy was received by 127 (42.1%) patients after excluding 15 (5.0%) patients with severe complications or PD after RT, and 160 (53.0%) patients received hepatectomy alone. In the randomized controlled trial (RCT), the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2% and 43.1%, respectively (P<0.001). In the two non-randomized studies, a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up (RR =2.02; 95% CI: 1.45–2.80; P<0.0001).ConclusionsThis systematic review showed that neoadjuvant RT followed by hepatectomy in patients with resectable HCC and PVTT was associated with a longer OS than patients who received hepatectomy alone.     

Comparative effectiveness of medical treatment vs. metabolic surgery for histologically proven non-alcoholic steatohepatitis and fibrosis: a matched network meta-analysis

BackgroundNon-alcoholic steatohepatitis (NASH) comprises a major healthcare problem affecting up to 30% of patients with obesity and the associated risk for cardiovascular and liver-related mortality. Several new drugs for NASH-treatment are currently investigated. No study thus far directly compared surgical and non-surgical therapies for NASH. This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.MethodsThe study was conducted according to the PRISMA guidelines for network meta-analysis. PubMed, CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy. Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected. Patients with liver cirrhosis were excluded. Risk of bias was assessed with ROB-2 and ROBINS-I-tools. A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied. Main outcomes were NASH-resolution and improvement of fibrosis.ResultsOut of 7,913 studies, twelve randomized non-surgical studies and twelve non-randomized surgical trials were included. NASH-resolution after non-surgical intervention was 29% [95% confidence interval (CI): 23–40%] and 79% (95% CI: 72–88%) after surgery. The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication [odds ratio (OR) =2.68; 95% CI: 1.44–4.97] while drug treatment was superior to placebo (OR =2.24; 95% CI: 1.55–3.24). Surgery (OR =2.18; 95% CI: 1.34–3.56) and medication (OR =1.79; 95% CI: 1.39–2.31) were equally effective to treat fibrosis compared to placebo without difference between them. The results did not change when only new drugs specifically developed for the treatment of NASH were included.ConclusionsMetabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis. Trials directly comparing surgery with medication must be urgently conducted. Patients with NASH should be informed about surgical treatment options.     

Cytoreductive stereotactic body radiotherapy (SBRT) and combination SBRT with immune checkpoint inhibitors in metastatic renal cell carcinoma

IntroductionPreclinical evidence demonstrates the immunogenic potential of stereotactic body radiotherapy (SBRT). There is growing interest in investigating this interplay with the immune system in metastatic renal cell carcinoma (mRCC). Cytoreduction with SBRT and combination therapy with SBRT and checkpoint inhibitor immuno-oncology agents (IO) are two potential therapeutic strategies in mRCC. In this review, we summarize the current clinical evidence for the use of cytoreductive SBRT to primary kidney and combination SBRT with IO.MethodsA literature review for articles and abstracts published between January 2000 and March 2020 was conducted through the PubMed, the American Society of Clinical Oncology (ASCO), and the American Society of Radiation Oncology (ASTRO) databases. Evaluation of studies followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) criteria.ResultsA total of three articles for cytoreductive SBRT and one article and three abstracts for combination SBRT and IO in mRCC met inclusion criteria for this review. Evidence for SBRT to primary kidney is limited by small series and pilot studies. Outcomes vary widely due to small patient numbers and study heterogeneity. Local control ranges from 85–100% and one- and two-year overall survival ranges from 38–71% and 19–53%, respectively. Combination SBRT and IO are tolerable for patients with early data, suggesting grade 3–4 adverse event rates of 0–24%. Long-term survival data is not yet available.ConclusionsCytoreductive SBRT and combination SBRT with IO therapy represent promising treatment strategies in mRCC. The evidence for clinical benefit is currently limited and requires further study with well-designed, randomized controlled trials.     

Intrahepatic bile duct recurrence of hepatocellular carcinoma without a detectable liver tumor

INTRODUCTIONInvasion of the portal and hepatic veins by hepatocellular carcinoma (HCC) is common, but macroscopic bile duct invasion is rare. Once a tumor thrombus completely obstructs the main bile duct, it causes obstructive jaundice. This type of HCC, known as icteric-type HCC (IHCC), has a poor prognosis.PRESENTATION OF CASEA 72-year-old woman had been treated for chronic hepatitis C since 1997. In 2002, percutaneous ethanol injection therapy was performed for HCC in segment 8. HCC recurrence occurred in 2004, and she underwent transarterial embolization (TAE) and radiofrequency ablation (RFA). In 2006, an S8 segmentectomy was performed for re-recurrence of HCC. Three years after surgery, computed tomography (CT) revealed a tumor occupying the right anterior intrahepatic bile duct and extending into its right main branch. With a preoperative diagnosis of HCC recurrence in the bile duct, we performed a right hepatectomy and thrombectomy. Histological examination showed moderately to poorly differentiated HCC. No tumor tissue other than the intrahepatic bile duct tumor was detected in the resected liver specimen.DISCUSSIONHCC with biliary tumor thrombus is associated with a poor prognosis. In general, IHCC is difficult to diagnose and treat in the early stages. A characteristic radiological finding for this type of IHCC is the hypervascularity of the tumor thrombus.CONCLUSIONTo the best of our knowledge, this is a rare case of IHCC recurrence as a tumor thrombus without recurrence in the resected liver specimen.     

Prognostic indicators for survival in renal cell carcinoma with venous thrombus and development of predictive nomograms

BackgroundPrevious predictive models of prognosis of patients with renal cell carcinoma (RCC) and venous tumour thrombus (VTT) didn’t included patients have not undergoing radical nephrectomy (RN). We analysed both patients receive RN or not to investigate the prognostic factors of survival for patients with RCC and VTT comprehensively.MethodsThe clinical data of patients with RCC and VTT diagnosed from 2000–2018 in the Surveillance Epidemiology and End Results (SEER) database were downloaded and compared with the clinical data of patients with VTT admitted to the Department of Urology of the Tongji Hospital (TJH) from 2004–2020. The matched cases were divided into a training set and a validation set. The training set was used to establish nomograms based on key prognostic factors. The reliability of the nomograms for predicting the survival of patients in the training set, those in the validation set and TJH patients and was evaluated by C-indexes, ROC curves and calibration curves.ResultsMultivariate Cox regression analysis identified nine prognostic factors for overall survival (OS): age, tumour size, histologic classification, nuclear grade, location of VTT, N stage, M stage, surgery, and systemic treatments (P<0.001). Nomograms for OS and cancer specific survival (CSS) were established based on key prognostic factors obtained from the multivariate analysis. The C-indexes of the nomogram for predicting OS in the training set, validation set, TJH cohort were 0.762 (95% CI: 0.746–0.778), 0.718 (95% CI: 0.687–0.749), and 0.819 (95% CI: 0.745–0.893), respectively. The calibration curves are all close to a straight line with a slope of 1. Based on the ROC curves, the nomograms had greater areas under the curve (AUCs) than the tumor, node and metastasis (TNM) staging system in predicting the 3-year OS and CSS. All three validations showed that the nomograms established based on key prognostic factors have reliable accuracy in predicting the survival of both TJH and SEER patients who developed RCCs with VTT.ConclusionsBeside the location of VTT, the tumour size can also predict the survival of patients with RCC and VTT. Nomograms based on key prognostic factors can predict the survival of patients from both America and central China with reliable accuracy.     

Efficacy and safety of immunological checkpoint inhibitors combined with anti-angiogenic drugs in first-line treatment of metastatic renal cell carcinoma: a systematic review and meta-analysis

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising results for the second-line treatment of metastatic renal cell carcinoma (mRCC). Several randomized controlled trials have so far also evaluated the efficacy of ICIs for first-line treatment of mRCC. In this study, we conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of ICIs combined with anti-angiogenic drugs for the treatment of mRCC.MethodsWe searched the PubMed, Embase, and Cochrane libraries for RCT trials of ICIs combined with anti-angiogenic drugs for first-line treatment of mRCC published before November 20, 2019. A meta-analysis was conducted based on methodological recommendations by the Cochrane Collaboration.ResultsFour articles with a total of 2,967 patients met the inclusion criteria. Our meta-analysis revealed that progression-free survival (PFS) and objective response rate (ORR) were significantly improved in the experimental group while there was no significant difference in overall survival (OS) (HR 0.75, 95% CI: 0.67–0.84; HR 1.43, 95% CI: 1.07–1.91; HR 0.74, 95% CI: 0.53–1.03). After stratification for PD-L1 expression, OS, PFS, and ORR of PD-L1 positive patients were significantly increased in the experimental group (HR 0.74, 95% CI: 0.56–0.96; HR 1.66, 95% CI: 1.11–2.49; HR 0.65, 95% CI: 0.57–0.75).ConclusionsImmunological checkpoint inhibitors combined with anti-angiogenic drugs as a first-line treatment for mRCC improve PFS and ORR. This effect is more pronounced in PD-L1 positive patients, where ICIs also improve OS. ICIs do not increase the incidence of adverse events.