Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis

BACKGROUNDGiven the poor synthetic function of cirrhotic liver, successful resection for patients with hepatocellular carcinoma (HCC) necessitates the ability to achieve resections with tumor free margins.AIMTo validate post hepatectomy liver failure score (PHLF), compare it to other established systems and to stratify risks in patients with cirrhosis who underwent curative liver resection for HCC. METHODSBetween December 2010 and January 2017, 120 patients underwent curative resection for HCC in patients with cirrhosis were included, the pre-operative, operative and post-operative factors were recorded to stratify patients'' risks of decompensation, survival, and PHLF.RESULTSThe preoperative model for end-stage liver disease (MELD) score [odds ratio (OR) = 2.7, 95%CI: 1.2-5.7, P = 0.013], tumor diameter (OR = 5.4, 95%CI: 2-14.8, P = 0.001) and duration of hospital stay (OR = 2.5, 95%CI: 1.5-4.2, P = 0.001) were significant independent predictors of hepatic decompensation after resection. While the preoperative MELD score [hazard ratio (HR) = 1.37, 95%CI: 1.16-1.62, P < 0.001] and different grades of PHLF (grade A: HR = 2.33, 95%CI: 0.59-9.24; Grade B: HR = 3.15, 95%CI: 1.11-8.95; Grade C: HR = 373.41, 95%CI: 66.23-2105.43; P < 0.001) and HCC recurrence (HR = 11.67, 95%CI: 4.19-32.52, P < 0.001) were significant independent predictors for survival.CONCLUSIONPreoperative MELD score and tumor diameter can independently predict hepatic decompensation. While, preoperative MELD score, different grades of PHLF and HCC recurrence can precisely predict survival.     

Does chronic kidney disease affect the complications and prognosis of patients after primary colorectal cancer surgery?

BACKGROUNDThe effect of chronic kidney disease (CKD) on the outcomes of colorectal cancer (CRC) patients after primary CRC surgery is controversial.AIMTo analyze whether CKD had specific effect on the outcomes after CRC surgery.METHODSWe searched the PubMed, Embase, Cochrane Library databases and CNKI, from inception to March 14, 2022. Newcastle-Ottawa Scale was used for the quality assessment in this meta-analysis, and we used RevMan 5.3 was used for data analysis.RESULTSA total of nine studies including 47771 patients were eligible for this meta-analysis. No significant difference was found in terms of overall postoperative complications [odds ratio (OR) = 1.78, 95%CI: 0.64-4.94, P = 0.27]. We analyzed the specific complications and found that the CKD group had higher rates of pulmonary infection (OR = 2.70, 95%CI: 1.82-4.00, P < 0.01), cardiovascular complications (OR = 3.39, 95%CI: 2.34-4.91, P < 0.01) and short-term death (OR = 3.01, 95%CI: 2.20-4.11, P < 0.01). After pooling the hazard ratio (HR), the CKD group had worse overall survival (OS) (HR = 1.51, 95%CI: 1.04-2.20, P = 0.03). We performed subgroup analyses of the dialysis and non-dialysis groups, and no significant difference was found in the non-dialysis group (HR = 1.20, 95%CI: 0.98-1.47, P = 0.08). The dialysis group had worse OS (HR = 3.36, 95%CI: 1.92-5.50, P < 0.01) than the non-dialysis group. The CKD group had worse disease-free survival (DFS) (HR = 1.41, 95%CI: 1.12-1.78, P < 0.01), and in the subgroup analysis of the dialysis and non-dialysis groups, no significant difference was found in the non-dialysis group (HR = 1.27, 95%CI: 0.97-1.66, P = 0.08). The dialysis group had worse OS (HR = 1.95, 95%CI: 1.23-3.10, P < 0.01) than the non-dialysis group.CONCLUSIONPreexisting CKD was associated with higher rates of pulmonary infection, higher rates of short-term death, and worse OS and poorer DFS following CRC surgery.     

Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy

BACKGROUNDA decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.AIMTo assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.METHODSWe retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary’s Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort.RESULTSWe included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response.CONCLUSIONIn advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.     

Laparoscopic vs. open surgery for gastrointestinal stromal tumors of esophagogastric junction: A multicenter,retrospective cohort analysis with propensity score weighting

Objective:Laparoscopic resection is increasingly performed for gastrointestinal stromal tumors(GISTs).However,the laparoscopic approach for GISTs located in the esophagogastric junction(EGJ-GIST)is surgically challenging.This study compares the efficacy of laparoscopic surgery and the open procedure for EGJ-GIST through the propensity score weighting(PSW)method.Methods:Between April 2006 and April 2018,1,824 surgical patients were diagnosed with primary gastric GIST at four medical centers in South China.Of these patients,228 were identified as EGJ-GISTs and retrospectively reviewed clinicopathological characteristics,operative information,and long-term outcomes.PSW was used to create the balanced cohorts.Results:PSW was carried out in laparoscopic and open-surgery cohorts according to year of surgery,sex,age,body mass index(BMI),tumor size,mitotic rates and recurrence risk.After PSW,438 patients consisting of 213 laparoscopic(L group)and 225 open surgery(O group)patients were enrolled.After PSW,the following measures in the L group were superior to those in the O group:median operative time[interquartile range(IQR)]:100.0(64.5-141.5)vs.149.0(104.0-197.5)min,P<0.001;median blood loss(IQR):30.0(10.0-50.0)vs.50.0(20.0-100.0)mL,P=0.002;median time to liquid intake(IQR):3.0(2.0-4.0)vs.4.0(3.0-5.0)d,P<0.001;median hospital stay(IQR):6.0(4.0-8.0)vs.7.0(5.0-12.0)d,P<0.001;and postoperative complications(10.3%vs.22.7%,P=0.001).The median follow-up was 55(range,2-153)months in the entire cohort.No significant differences were detected in either relapse-free survival(RFS)[hazard ratio(HR):0.372,95%confidence interval(95%CI):0.072-1.910,P=0.236]or overall survival(OS)(HR:0.400,95%CI:0.119-1.343,P=0.138)between the two groups.Conclusions:Laparoscopic surgery for EGJ-GIST is associated with the advantages of shorter operative time,reduced blood loss,shorter time to liquid intake,and shorter length of stay,all without compromising postoperative outcomes and long-term survival.     

Prognostic impact of at least 12 lymph nodes after neoadjuvant therapy in rectal cancer: A meta-analysis

BACKGROUNDThe number of dissected lymph nodes (LNs) in rectal cancer after neoadjuvant therapy has a controversial effect on the prognosis.AIMTo investigate the prognostic impact of the number of LN dissected in rectal cancer patients after neoadjuvant therapy.METHODSWe performed a systematic review and searched PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library from January 1, 2000 until January 1, 2020. Two reviewers examined all the publications independently and extracted the relevant data. Articles were eligible for inclusion if they compared the number of LNs in rectal cancer specimens resected after neoadjuvant treatment (LNs ≥ 12 vs LNs < 12). The primary endpoints were the overall survival (OS) and disease-free survival (DFS).RESULTSNine articles were included in the meta-analyses. Statistical analysis revealed a statistically significant difference in OS [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.66-0.88, I² = 12.2%, P = 0.336], DFS (HR = 0.76, 95%CI: 0.63-0.92, I² = 68.4%, P = 0.013), and distant recurrence (DR) (HR = 0.63, 95%CI: 0.48-0.93, I² = 30.5%, P = 0.237) between the LNs ≥ 12 and LNs < 12 groups, but local recurrence (HR = 0.67, 95%CI: 0.38-1.16, I² = 0%, P = 0.348) showed no statistical difference. Moreover, subgroup analysis of LN negative patients revealed a statistically significant difference in DFS (HR = 0.67, 95%CI: 0.52-0.88, I² = 0%, P = 0.565) between the LNs ≥ 12 and LNs < 12 groups.CONCLUSIONAlthough neoadjuvant therapy reduces LN production in rectal cancer, our data indicate that dissecting at least 12 LNs after neoadjuvant therapy may improve the patients’ OS, DFS, and DR.     

Comparison of portal and capsular microscopic vascular invasion in the outcomes of early HCC after curative resection

Microscopic vascular invasion (MVI) is a strong risk factor associated with tumor recurrence and poor overall survival (OS) among hepatocellular carcinoma (HCC) patients after resection. Two types of MVI are identified: portal vein and capsular vein invasion. However, little is known about the impact of different types of MVI on HCC recurrence. The present study aimed to compare HCC recurrence and OS between the portal vein and capsule vein MVI. Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection between January 2001 and June 2016 were consecutively recruited. Factors that influenced OS and recurrence-free survival (RFS) were analyzed using Cox proportional hazards models. Of the 857 eligible patients, 327 (38.2%) had MVI, and 530 (61.8%) were without MVI. Of the 327 patients with MVI, 85 (26.0%) were with portal vein, 178 (54.4%) with capsular vein, and 64 (19.6%) with both-MVI type. Patients with both-MVI type suffered from a higher proportion of BCLC stage A (P < 0.001), capsular invasion (P = 0.002), and satellite nodules (P < 0.001). Both-MVI type is an independent risk factor for HCC recurrence (hazard ratio [HR]: 1.69; 95% CI, 1.22-2.36, P = 0.002) and mortality (HR: 2.29; 95% CI, 1.59-3.29, P < 0.001) compared with non-MVI. We further found that both-MVI type was significantly associated with a higher risk of extrahepatic recurrence (EHR) (HR: 8.74; 95% CI, 2.38-32.03, P = 0.001). Among HCC patients after curative resection, concurrent portal and capsular MVI is a risk factor for HCC recurrence, especially for EHR, in comparison with non-MVI or only portal or capsular MVI alone.     

Nomogram for the prediction of lymph node metastasis and survival outcomes in rectal neuroendocrine tumour patients undergoing resection

BackgroundThe current study analysed rectal neuroendocrine tumour (RNET) patients undergoing resection to identify predictive factors and construct nomograms for lymph node metastasis, cancer-specific survival (CSS) and overall survival (OS).MethodsRNET patients registered in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Multivariable logistic regression analysis was used to investigate the relationships between clinicopathological factors and lymph node metastasis. A multivariate competing risk model was applied to investigate factors independently associated with CSS. Through the Cox regression model, a multivariable analysis of OS was performed. Nomograms were established based on independent predictive factors. Calibration plots, receiver operating characteristic (ROC) curves and Brier scores were used to evaluate the predictive accuracy of the nomograms.ResultsIn this study, 1,253 RNET patients were included for further analysis. Tumour size ≥12 mm (P<0.001), T3/T4 stage (P<0.001) and M1 stage (P=0.001) were independently associated with lymph node metastasis. The performance of the nomogram was acceptable for predicting lymph node metastasis, with an area under the ROC curve (AUC) of 0.937 [95% confidence interval (CI): 0.874–1.000]. Calibration curves and the Hosmer-Lemeshow test revealed desirable model calibration (P=0.99996). The multivariate competing risk model analysis showed that grade II (P=0.017), tumour size ≥12 mm (P=0.007), AJCC TNM stage II (P=0.002), stage III (P<0.001) and stage IV (P<0.001) were significantly associated with worse CSS. In the competing risk nomogram model, the time-dependent AUC revealed good discriminatory ability of the model (time from 1 to 107 months, AUC >0.900), and the Brier score showed good accuracy of the nomogram, which was greater than that of the AJCC TNM stage. Multivariate Cox analysis showed that age >60 years (P=0.002), median income ≥$65,000 (P=0.013), AJCC TNM stage III (P=0.038) and AJCC TNM stage IV (P<0.001) were independently associated with worse OS. In the nomogram for the prediction of OS, the C-statistic was 0.703 (95% CI: 0.615–0.792), which was significantly better than that of the AJCC TNM stage (0.703 vs. 0.607, P=0.009). A calibration plot for the probability of survival demonstrated good calibration.ConclusionsThe present study is the first to establish nomograms with great discrimination and accuracy for the prediction of lymph node metastases, CSS and OS in RNET patients, which can be used to guide treatment decision-making and surveillance.     

Impact of spontaneous rupture on the survival outcomes after liver resection for hepatocellular carcinoma: A propensity matched analysis comparing ruptured versus non-ruptured tumors

IntroductionSpontaneous rupture of HCC (srHCC) is a life-threatening sequela of HCC characterized by a high mortality. Liver resection (LR) is the ideal therapeutic strategy as it not only arrests hemorrhage but also remove the offending tumour. We sought to determine the impact of spontaneous rupture on the survival outcomes of patients after LR by performing a propensity score matched (PSM) analysis comparing patients who underwent LR for srHCC versus non-ruptured (nrHCC).MethodsFrom 2000 to 2015, a total of 67 patients who underwent LR for srHCC which met the study criteria were included. 1:2 PSM was performed comparing 49 of 67 patients with srHCC with 98 nrHCC selected from a cohort of 724 patients who underwent LR during the study period.ResultsMedian survival following LR for srHCC was 21.9 months, while 5-year overall survival (OS) and disease-free survival (DFS) was 43.1% and 19.4% respectively. After 1:2 PSM analysis, there was no significant difference between LR for srHCC (n = 49) versus nrHCC (n-98) in terms of OS [21.9 (interquartile range (IQR), 11.8–44.0 vs 27.4 (IQR, 6.9–57.8) months, HR 1.02, CI 0.63–1.66, p = 0.94], DFS [11.8 (IQR, 5.6–25.6) vs 13.77 (IQR,4.5–34.9) HR 0.74, CI 0.54–1.02, p = 0.06] and length of stay [8 (IQR, 7–11) vs 7 (IQR, 6–10) HR 0.93, CI 0.0.68–1.29), p = 0.68].ConclusionLR for clinically stable patients with srHCC provides survival and recurrence outcomes that are comparable to patients with nrHCC.     

The effect of the TP53 and RB1 mutations on the survival of hepatocellular carcinoma patients with different racial backgrounds

BackgroundRacial disparities in the survival of patients with hepatocellular carcinoma (HCC) exist. Gene mutations have a profound effect on carcinogenesis, are easily affected by environment and etiology factors, and may result in survival divergences among patients with different racial backgrounds. This report explores the effects of gene mutations on the survival of American Caucasians and Asian patients.MethodsThe sequencing and clinical data of 336 HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. The sequencing data was subject to gene mutation profiling, and an analysis of immune cell infiltration was conducted. A multivariate analysis was performed to assess the independent effects of gene mutations on patients’ overall survival (OS) and disease-free survival (DFS).ResultsAsian HCC patients had a significantly higher level of TP53 mutation frequency than Caucasian HCC patients (Asian vs. Caucasian, 39% vs. 23%; P=0.003). The TP53 mutation was associated with shorter OS [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.36–3.97; P=0.002] and DFS (HR, 2.2; 95% CI, 1.38–3.51; P<0.001) in Caucasian HCC patients, but had no effect on Asian HCC patients’ survival. Compared to Asian HCC patients, Caucasian HCC patients with the TP53 mutation had a decreased proportion of infiltrating M2 macrophages and activating natural killer (NK) cells, and an increased proportion of follicular helper T cells. The RB1 mutation was associated with shorter OS (HR, 3.37; 95% CI, 1.73–6.57; P<0.001) in Asian HCC patients, and shorter DFS (HR, 2.11; 95% CI, 1.15–3.88; P=0.017) in Caucasian HCC patients. Asian HCC patients with the RB1 mutation had a decreased proportion of infiltrating CD8 T cells.ConclusionsThe effects of the TP53 and RB1 mutations on survival differ among Asian and Caucasian HCC patients.     

Anatomical vs nonanatomical liver resection for solitary hepatocellular carcinoma: A systematic review and meta-analysis

BACKGROUNDThe long-term survival of patients with solitary hepatocellular carcinoma (HCC) following anatomical resection (AR) vs non-anatomical resection (NAR) is still controversial. It is necessary to investigate which approach is better for patients with solitary HCC.AIMTo compare perioperative and long-term survival outcomes of AR and NAR for solitary HCC.METHODSWe performed a comprehensive literature search of PubMed, Medline (Ovid), Embase (Ovid), and Cochrane Library. Participants of any age and sex, who underwent liver resection, were considered following the following criteria: (1) Studies reporting AR vs NAR liver resection; (2) Studies focused on primary HCC with a solitary tumor; (3) Studies reporting the long-term survival outcomes (> 5 years); and (4) Studies including patients without history of preoperative treatment. The main results were overall survival (OS) and disease-free survival (DFS). Perioperative outcomes were also compared.RESULTSA total of 14 studies, published between 2001 and 2020, were included in our meta-analysis, including 9444 patients who were mainly from China, Japan, and Korea. AR was performed on 4260 (44.8%) patients. The synthetic results showed that the 5-year OS [odds ratio (OR): 1.19; P < 0.001] and DFS (OR: 1.26; P < 0.001) were significantly better in the AR group than in the NAR group. AR was associated with longer operating time [mean difference (MD): 47.08; P < 0.001], more blood loss (MD: 169.29; P = 0.001), and wider surgical margin (MD = 1.35; P = 0.04) compared to NAR. There was no obvious difference in blood transfusion ratio (OR: 1.16; P = 0.65) or postoperative complications (OR: 1.24, P = 0.18).CONCLUSIONAR is superior to NAR in terms of long-term outcomes. Thus, AR can be recommended as a reasonable surgical option in patients with solitary HCC.     

Microwave ablation vs. surgical resection for treatment naïve hepatocellular carcinoma within the Milan criteria: a follow-up of at least 5 years

Objective:Thermal ablation poses challenges in the surgical resection (SR) of small hepatocellular carcinoma (HCC), and its therapeutic outcomes for larger lesions remain debated.Methods:This retrospective study evaluated 729 patients with HCC meeting the Milan criteria, who were treated with curative SR or microwave ablation (MWA) between 2008 and 2014. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and local tumor progression (LTP) were compared after propensity score matching (PSM). Co-variates associated with OS, CSS, LTP, and DFS were identified. The risk of death and tumor progression were compared.Results:During the median follow-up of 78.6 months, 253 patients were included in each group after PSM. For tumors ≤ 3.0 cm and 3.1–4.0 cm, MWA achieved comparable results in terms of OS, CSS, DFS, and LTP. For tumors 4.1–5.0 cm, MWA had lower OS, CSS, and DFS rates (all P < 0.05) than SR. Higher LTP rates were observed in the MWA group for tumors 4.1–5.0 cm, although the difference was not significant (P = 0.18). Complication rates (P = 0.41) were similar, but MWA led to less estimated blood loss (P < 0.01) and shorter postoperative hospitalization times (P < 0.01).Conclusions:MWA achieved comparable long-term oncologic outcomes with SR for ≤ 4 cm HCC, with lower complication rates and faster recovery.     

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

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

A novel, externally validated inflammation-based prognostic algorithm in hepatocellular carcinoma: the prognostic nutritional index (PNI)

Background:

There is increasing evidence that the presence of an ongoing systemic inflammatory response is a stage-independent predictor of poor outcome in patients with cancer. The aim of this study was to investigate whether an inflammation-based prognostic score, the prognostic nutritional index (PNI), is associated with overall survival (OS) in patients with hepatocellular carcinoma (HCC).

Methods:

All patients with a new diagnosis of HCC presenting to the Medical Oncology Department, Hammersmith Hospital between 1993 and 2011 (n=112) were included. Demographic and clinical data were collected. Patients in whom the combined albumin (g l⁻¹) × total lymphocyte count × 10⁹ l⁻¹ was ⩾45, at presentation, were allocated a PNI score of 0. Patients in whom this total score was <45 were allocated a score of 1. Univariate and multivariate analyses were performed to identify clinicopathological variables associated with OS. Independent predictors of survival identified on multivariate analysis were validated in an independent, stage-matched cohort of 68 patients.

Results:

Univariate analyses showed that PNI (P=0.003), intrahepatic spread (P<0.001), the presence of extrahepatic disease (P=0.006), portal vein thrombosis (P=0.02), tumour multifocality (P=0.003), alfa-fetoprotein >400 ng ml⁻¹ (P<0.001) and Barcelona Clinic Liver Cancer score (P<0.01) were all predictors of OS in the training set. Multivariate analysis revealed the PNI (P=0.05), presence of extrahepatic disease (P<0.001) and degree of intrahepatic spread (P<0.001) as independent predictors of worse OS in this population. The PNI retained independent prognostic value in the validation set (P<0.001).

Conclusion:

The presence of a systemic inflammatory response, as measured by the PNI, is an independent and externally validated predictor of poor OS in patients with HCC.     

Anatomic resection improved the long-term outcome of hepatocellular carcinoma patients with microvascular invasion: A prospective cohort study

BACKGROUNDThe long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types.AIMTo explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI.METHODSA total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group.RESULTSIn the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491). CONCLUSIONFor patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.     

Impact of concurrent splenectomy and esophagogastric devascularization on surgical outcomes of partial hepatectomy for hepatocellular carcinoma in patients with clinically significant portal hypertension: A multicenter propensity score matching analysis

PurposePortal hypertension due to cirrhosis is common among patients with hepatocellular carcinoma (HCC). This study aimed to compare the outcomes of partial hepatectomy in patients with HCC and clinically significant portal hypertension (CSPH) with or without concurrent splenectomy and esophagogastric devascularization (CSED).Patients and methodsFrom a multicenter database, patients with HCC and CSPH who underwent curative-intent hepatectomy were identified. Postoperative morbidity and mortality, and long-term overall survival (OS) were compared in patients with and without CSED before and after propensity score matching (PSM).ResultsOf the 358 enrolled patients, 86 patients underwent CSED. Before PSM, the postoperative 30-day morbidity and mortality rates were comparable between the CSED and non-CSED group (both P > 0.05). Using PSM, 81 pairs of patients were created. In the PSM cohort, the 5-year OS rate of the CSED group were significantly better than the non-CSED group (52.9% vs. 36.5%, P = 0.046). The former group had a significantly lower rate of variceal bleeding on follow-up (7.4% vs. 21.7%, P = 0.014). On multivariate analysis, CSED was associated with significantly better OS (HR: 0.39, P < 0.001).ConclusionHepatectomy and CSED can safely be performed in selected patients with HCC and CSPH, which could improve postoperative prognosis by preventing variceal bleeding, and prolonging long-term survival.     

College of American Pathologists Tumor Regression Grading System for Long-Term Outcome in Patients with Locally Advanced Rectal Cancer

BackgroundThe National Comprehensive Cancer Network''s Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of the AJCC/CAP TRG system has not been fully defined.Materials and MethodsThis was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed a validation set to verify the findings from discovery set. Overall survival (OS), disease‐free survival (DFS), local recurrence‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were assessed by Kaplan‐Meier analysis, log‐rank test, and Cox regression model.ResultsThe discovery set (940 cases) found, and the validation set (2,156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely /ccorrelated with unfavorable survival (OS, DFS, LRFS, and DMFS) and higher risk of disease progression (death, accumulative relapse, local recurrence, and distant metastasis) (all p < .05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pathological complete response) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS, and DMFS (all p > .05). For AJCC/CAP TRG1–3 cases, adjuvant chemotherapy treatment significantly improved 3‐year OS (90.2% vs. 84.6%, p < .001). Multivariate analysis demonstrated the AJCC/CAP TRG system was an independent prognostic surrogate.ConclusionAJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.Implications for PracticeThe National Comprehensive Cancer Network recommends the American Joint Committee of Cancer and College of American Pathologists (AJCC/CAP) tumor regression grading (TRG) four‐category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer; however, the clinical significance of the AJCC/CAP TRG system has not yet been clearly addressed. This study found, for the first time, that any two of four AJCC/CAP TRG categories had the distinguished long‐term survival outcome. Importantly, adjuvant chemotherapy may improve the 3‐year overall survival for AJCC/CAP TRG1–3 category patients but not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long‐term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.     

ALBI grade in dialysis patients with hepatocellular carcinoma: prognostic impact and staging strategy

BackgroundPatients with hepatocellular carcinoma (HCC) may develop end-stage renal disease and receive dialysis, but the impact of dialysis on the prognosis is unclear. This study aimed to evaluate the outcome of dialysis HCC patients and the prognostic role of albumin-bilirubin (ALBI) grade in these patients.MethodsAmong the consecutive 3,794 HCC patients between 2002–2017, 43 patients undergoing dialysis, and 129 age, sex-matched controls were analyzed. Multivariate Cox hazards model was used to identify independent prognostic predictors.ResultsDialysis patients had decreased overall survival when compared with non-dialysis patients (n=3,751) and matched controls (n=129; each P=0.004). Patients with ALBI grade 1 had the best survival in the pooled cohort of dialysis and matched controls (n=172). In the Cox model, total tumor volume >33 cm³ [hazard ratio (HR): 6.763, P<0.001], presence of ascites (HR: 6.168, P<0.001), dialysis duration less than 24 months (HR: 3.144, P=0.006), diabetes-related dialysis (HR: 9.366, P=0.001) and non-curative treatments (HR: 9.220, P<0.001) were poor prognosis factors associated with increase mortality among dialysis patients. Of the 9 currently-used HCC staging systems, the CLIP score was the optimal cancer staging for dialysis patients.ConclusionsPatients receiving dialysis had decreased overall survival compared with non-dialysis patients. Longer duration of dialysis, non-diabetes related dialysis, absence of ascites, and curative treatments were associated with improved survival in these patients. The ALBI grade is a feasible prognostic model to evaluate liver functional reserve, and the CLIP model is the best staging system for dialysis patients with HCC.     

Decreased albumin-to-alkaline phosphatase ratio predicted poor survival of resectable gastric cancer patients

BackgroundThe albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown.MethodsWe retrospectively reviewed 227 resectable GC patients in our center. The Kaplan–Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS predictionResultsThe AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ² for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system.ConclusionsThe AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.     

Therapeutic efficacy of combined BRAF and MEK inhibition in metastatic melanoma: a comprehensive network meta-analysis of randomized controlled trials

Background

Several recent randomized clinical trials have preliminarily demonstrated that initial targeted therapy with combined BRAF and MEK inhibition is more effective in metastatic melanoma (MM) than single agent. To guide therapeutic decisions, we did a comprehensive network meta-analysis to identify evidence to robustly support whether combined BRAF and MEK inhibition is the best initial targeted therapeutic strategy for patients with MM.

Methods

The databases of PubMed and trial registries were researched for randomized clinical trials of targeted therapy. Data of outcome were extracted on progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Network meta-analysis using a Bayesian statistical model was performed to evaluate relative hazard ratio (HR) for PFS and OS, odds ratio (OR) for ORR.

Results

Finally, 16 eligible trials comprising 5976 participants were included in this meta-analysis. PFS were significantly prolonged in patients who received combined BRAF-MEK inhibition compared with those who received BRAF inhibition (HR: 0.58, 95%CI: 0.51-0.67, P < 0.0001) or MEK inhibition alone (HR: 0.29, 95%CI: 0.22-0.37, P < 0.0001). Combined BRAF-MEK inhibition also improved the OS over BRAF inhibition (HR: 0.67, 95%CI: 0.56-0.81, P < 0.0001) or MEK inhibition alone (HR: 0.48, 95%CI: 0.36-0.65, P < 0.0001). The ORR was superior in combined BRAF and MEK inhibition comparing with BRAF inhibition (OR: 2.00, 95%CI: 1.66-2.44, P < 0.0001) or MEK inhibition alone (OR: 20.66, 95%CI: 12.22-35.47, P < 0.0001).

Conclusions

This study indicates that concurrent inhibition of BRAF and MEK improved the most effective therapeutic modality as compared as single BRAF or MEK inhibition for patients with MM.     

Adjuvant transarterial chemoembolization improves survival outcomes in hepatocellular carcinoma with microvascular invasion: A systematic review and meta-analysis

BackgroundThe benefits of adjuvant transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) remain controversial. We compared the efficacy and safety of adjuvant TACE and hepatic resection (HR) alone for HCC patients with MVI.MethodsThe PubMed, EMBASE, Cochrane Library, VIP, Wan Fang, and Sino Med databases were systematically searched to compare adjuvant TACE and HR alone for the treatment of HCC with MVI from inception to January 1, 2019. The study outcomes, including overall survival (OS) and disease-free survival (DFS), were extracted independently by two authors.Results12 trials involving 2190 patients were evaluated. A meta-analysis of 11 studies suggested that the 1-, 3-, and 5-year overall survival (OS) rates (OR = 0.33, P < 0.001; OR = 0.49, P < 0.001; and OR = 0.59, P < 0.01; respectively), favored adjuvant TACE over HR alone. 11 studies were included in the meta-analysis of DFS, and adjuvant TACE showed better 1-, 3-, and 5-DFS (OR = 0.45, P < 0.001; OR = 0.50, P < 0.001; and OR = 0.58, P < 0.001; respectively) compared to HR alone. Subgroup analysis demonstrated that adjuvant TACE could benefit HCC patients with MVI with tumor diameter >5 cm or multinodular tumors.ConclusionAdjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI. However, these results need to be validated through further high-quality clinical studies.Lay summaryThe benefits of adjuvant TACE in HCC patients with microvascular invasion remain controversial. Twelve studies involving 2190 patients were include in our meta-analysis. Adjuvant TACE may improve OS and DFS for HCC patients with MVI compared to HR alone and should be recommended for selected HCC patients with MVI.