Risk Factor For Poor Survival Research Articles

High-Intensity Focused Ultrasound Ablation for Unresectable Primary and Metastatic Liver Cancer: Real-World Research in a Chinese Tertiary Center With 275 Cases.

This retrospective analysis was conducted to evaluate the feasibility and safety of high-intensity focused ultrasound ablation for primary liver cancer and metastatic liver cancer. Patients with liver cancer who received high-intensity focused ultrasound were included in this analysis, including a primary liver cancer cohort (n=80) and a metastatic liver cancer cohort (n=195). The primary endpoint of our research was tumor response. The secondary endpoints included survival outcomes, visual analog scale pain scores, alpha-fetoprotein relief, and complications. Objective response rate and disease control rate were observed to be 71.8% and 81.2%, respectively, in patients with primary liver cancer and were 63.7% and 83.2% in cases with metastatic liver cancer. Alpha-fetoprotein levels and visual analogue scale levels significantly decreased after treatment compared with the baseline levels in patients with primary liver cancer (p<0.05). Median overall survival was estimated to be 13.0 and 12.0 months in the primary liver cancer and metastatic liver cancer cohorts. The 1-year survival rate was 70.69% and 48.00%, respectively. Multivariate regression analysis showed that visual analogue scale ≥ 5, longest diameter ≥ 5 cm, and portal vein invasion were the independent risk factors for poor survival in primary liver cancer. For patients with metastatic liver cancer, independent risk factors were identified as visual analogue scale ≥ 5, longest diameter ≥ 5 cm, existence of extrahepatic metastases, existence of portal vein invasion, and time to high-intensity focused ultrasound treatment from diagnosis < 3 months. Severe adverse events were rarely reported. In conclusion, high-intensity focused ultrasound might be an effective and safe option for patients with liver cancer regardless of primary and metastatic lesions.

Long-term outcome after early repair of complete atrioventricular septal defect in young infants

ObjectiveThe long-term outcome after repair of complete atrioventricular septal defect in young infants is still not fully understood. The objective of this study was to evaluate data after repair for complete atrioventricular septal defect over a 25-year period to assess survival and identify risk factors for left atrioventricular valve–related reoperations. MethodsA total of 304 consecutive patients underwent surgical correction for complete atrioventricular septal defect between April 1993 and October 2018. The results for young infants (aged <3 months; n = 55; mean age 1.6 ± 0.6 months) were compared with older infants (aged >3 months; n = 249; mean age, 5.1 ± 5.2 months). Mean follow-up was 13.2 ± 7.8 years (median, 14.0 years; interquartile range, 7.0-20.0). The Kaplan–Meier method was used to assess overall survival and freedom from left atrioventricular valve–related reoperation. ResultsOverall, 30-day mortality was 1.0% (3/304) with no difference between young and older infants (P = 1.0). Overall survival in the total population at 20-year follow-up was 95.1% (±1.3%). Independent risk factors for poor survival were the presence of an additional ventricular septal defect (P = .042), previous coarctation of the aorta (P < .001), persistent left superior vena cava (P = .026), and genetic syndromes other than Trisomy 21 (P = .017). Freedom from left atrioventricular valve–related reoperation was 92.6% (±1.7%) at 20 years. There was no significant difference in left atrioventricular valve–related reoperation in young infants compared with older infants (P = .084). ConclusionsOur data demonstrated that excellent long-term survival could be achieved with early repair for complete atrioventricular septal defect, and the need for reoperations due to left atrioventricular valve regurgitation was low. Primary correction in patients aged less than 3 months is, when clinically necessary, well tolerated. Palliative procedures can be avoided in the majority of patients.

Poorer prognosis of ovarian squamous cell carcinoma than serous carcinoma: a propensity score matching analysis based on the SEER database

BackgroundOvarian squamous cell carcinoma (SCC) is a rare cancer with possible poor survival, however no direct evidence supports this viewpoint and the independent prognostic factors are controversial. Patients with ovarian SCC and serous carcinoma (SC) who were diagnosed between 2004 and 2016 were selected using the recent released SEER database. Propensity score matching was used to balance the characteristics of the two groups. The difference of survival between patients with ovarian SCC and SC was explored using Kaplan-Meier method. Cox regression analyses were performed to further identify the independent prognostic factors among patients with ovarian SCC.ResultsOf 15,286 patients (15,106 SC cases and 180 SCC cases), 304 were identified in the matched cohort (200 SC cases and 104 SCC cases). The overall survival and cause-specific survival for patients with SCC were significantly poorer (Plog-rank < 0.001). The median survival time was 21 months for SCC and 95 months for SC. Patients who underwent bilateral salpingo-oophorectomy with hysterectomy and omentectomy seemed to have a better outcome. In multivariate analysis, older age at diagnosis, larger tumor size, bilateral and FIGO stage IV malignancy were the independent risk factors for poor disease outcome.ConclusionsThe prognosis of ovarian SCC is worse than ovarian SC. Older age at diagnosis, advanced disease stage, larger tumor size and bilateral malignancy are the independent risk factors for poor survival.

Retrospective analysis of long-term outcome 10 years after liver transplantation for Wilson disease: experience over three decades.

We evaluated long-term outcomes for patients with Wilson disease (WD) after liver transplantation (LT) and searched for risk factors for poor survival. Retrospective analysis of UNOS/OPTN data identified 156 pediatric and 515 adult cases of LT for WD between 1987 and 2016. Comparison cases were 10442 pediatric and 104874 adult non-WD transplant recipients. Survival was calculated using Kaplan-Meier analysis. Recipient, donor, and surgical variables were compared by Cox regression. Survival rates 3, 5, and 10years after LT for adult WD patients (87.5%, 85.4%, and 80.5%, respectively) were significantly higher than those for non-WD patients (P<0.001); survival rates for pediatric WD patients (90.5%, 89.7%, and 86.5%, respectively) did not differ significantly from non-WD patients. Graft survival in adult and pediatric patients followed similar trends. Regression analysis identified older age, female gender, and use of life support at the time of transplant as risk factors for decreased survival for adults with WD, and younger age, male gender, obesity, and high serum creatinine at the time of transplant as risk factors for poor survival in pediatric recipients with WD. Presentation with fulminant liver failure was not associated with survival in WD patients. No donor characteristic predicted poor survival. Long-term patient and graft survival after LT is excellent for both adult and pediatric WD patients.

Impact of Type 2 Diabetes on Oncologic Outcomes of Hepatocellular Carcinomas in Non-Cirrhotic, Non-alcoholic Steatohepatitis: a Matched-Pair Analysis

BackgroundNon-alcoholic steatohepatitis (NASH) associated hepatocellular carcinomas (NASH-HCC) are increasing. NASH-HCC often develops in the fibrotic liver. Several analyses report conflicting results regarding the outcome of non-cirrhotic NASH-HCC. Furthermore, type 2 diabetes (T2D) is considered a risk factor for poor survival. The aim of this study was to investigate oncological outcomes of non-cirrhotic NASH-HCC and the impact of T2D. MethodsPatients with non-cirrhotic NASH-HCC with T2D as determined by an expert pathologist conducting histological slide review were matched for risks factors for poor outcome (age, gender, body mass index) with patients with NASH-HCC without T2D. These patients were then matched 1:1 with HCCs of other underlying liver diseases with and without T2D. Oncological outcomes were assessed using Kaplan-Meier curves. ResultsOut of 365 HCCs resected between 2001 and 2017, 34 patients with non-cirrhotic NASH-HCC were selected (17 with T2D, 17 without T2D) and matched with 26 patients with hepatitis-HCC and 28 patients with alcohol-related HCC. Oncological risk factors such as tumor size, resection margin, and vessel invasion were comparable. There was no difference in overall survival (5-year survival 71.3% for NASH-HCC, 60.4% for hepatitis-HCC, 79.9% for alcohol-HCC). NASH-HCC was associated with longer disease-specific survival than hepatitis-HCC (5-year 87.5% vs. 63.7%, p = 0.048), while recurrence-free survival was identical. T2D had no impact on oncological outcomes in either liver disease. ConclusionNon-cirrhotic NASH-HCC has outcomes comparable with other underling etiologies. Despite a lack of cirrhosis, patients with non-cirrhotic NASH-HCC have the same risks of HCC recurrence as patients with cirrhotic liver disease of other etiologies.

Extrapancreatic Nerve Plexus Invasion on Imaging Predicts Poor Survival After Upfront Surgery for Anatomically Resectable Pancreatic Cancer.

This study aimed to analyze the risk factors for poor survival of the patients with anatomically resectable pancreatic ductal adenocarcinoma (PDAC), focusing on detailed computed tomography (CT) findings of tumor extent to the peripancreatic tissue. The study included 192 patients who underwent upfront pancreaticoduodenectomy for anatomically resectable PDAC. Preoperative CT images were rereviewed by an experienced radiologist for the pattern of tumor extension to the surrounding tissue: biliary, duodenal, serosal, retroperitoneal, portal venous, arterial, extrapancreatic nerve plexus, and other-organ invasion. Imaging findings and other clinical data that could be obtained before surgery were evaluated for their association with a shorter disease-specific survival (DSS) and recurrence-free survival (RFS). Of the 192 anatomically resectable PDAC patients, extrapancreatic nerve plexus invasion was observed on CT in 38 patients (20%), and this finding was independently associated with a shorter DSS (hazard ratio, 2.258; P < 0.001) and RFS (hazard ratio, 2.665; P < 0.001). The median survival of patients with and without extrapancreatic nerve plexus invasion on CT was 19.7 versus 38.5 months (P < 0.001). Extrapancreatic nerve plexus invasion was shown as an only CT finding associated with a shorter DSS and RFS after upfront surgery for the patients with anatomically resectable PDAC.

Acral lentiginous melanoma: a single-centre retrospective review of four decades in East-Central Europe.

Acral lentiginous melanoma (ALM) occurs on the palms, soles and subungual surface and has poor prognosis. It is uncommon in the Caucasian population and has remained unreported in East-Central Europe. Our aim was to collect data from East-Central Europe by analysing the demographic and clinicopathologic features of patients with ALM and comparing data with the reports in literature. We conducted a single-centre, retrospective review between 1976 and 2016 at one of the largest melanoma referral centres in Hungary. We identified 176 patients with ALM (3.83%) from 4593 patients with melanoma (mean age: 66.2years). The tumours were mainly located on the lower extremities (88.63%). The mean Breslow tumour thickness was 3.861mm, 37.50% of the tumours were thicker than 4.00mm, and 71.6% exhibited microscopic ulceration. Nearly one-third of the patients underwent sentinel lymph node (SLN) biopsy, and 60.3% of the biopsies were positive for metastasis. The positive SLN status was associated with significantly thick tumours and reduced survival. Patients with ALM had 5- and 10-year overall survival rates of 60.5% and 41.6%, respectively. The mean delay in diagnosis was 18months after the discovery of skin tumours. In multivariate analyses, age, tumour thickness and distant metastasis were independent risk factors for poor survival (P<0.001). Our study, which is the first single-centre report in East-Central Europe focusing on ALM, confirms that patient and tumour characteristics and prognostic factors are similar with previous literature data involving Caucasians; however, tumour thickness and survival suggest even worse prognosis.

Prognostic Value of the C-Reactive Protein/Lymphocyte Ratio in Pancreatic Cancer.

Many inflammatory markers can be used for the prognostication of pancreatic cancer, but which combination of inflammatory factors may be the best remains unclear. This study focused on the potential feasibility of the newly discovered C-reactive protein (CRP)/lymphocyte ratio (CLR) as a prognostic biomarker for patients with pancreatic cancer. The study enrolled 997 patients with pancreatic cancer. Six combinations of inflammatory markers, namely, the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), the CRP/albumin ratio (CAR), the neutrophil/albumin ratio (NAR), the platelet/albumin ratio (PAR), and CLR, were examined to determine which combination offers the highest accuracy for predicting poor survival by receiver operating characteristic curve analysis. The prognostic value of the CLR was analyzed by uni- and multivariate analyses. The newly developed CLR was more accurate than the NLR, PLR, CAR, NAR, and PAR in predicting survival. The optimal cutoff value for the CLR was calculated to be 1.8 for survival. A CLR higher than 1.8 was associated with poor survival in both the univariate (hazard ratio [HR] 2.00; P < 0.001) and multivariate (HR 1.73; P < 0.001) analyses. In addition, a CLR higher than 1.8 was an independent risk factor for patients with stage 2 (HR 1.85; P = 0.001), stage 3 (HR 1.83; P = 0.001), or stage 4 (HR 1.70; P < 0.001) disease. Pretreatment CLR can be considered a feasible biomarker for the prognostic prediction of pancreatic cancer. An elevated CLR was an independent risk factor for poor survival, with a cutoff value of 1.8.

Relevance and prognostic ability of Twist, Slug and tumor spread through air spaces in lung adenocarcinoma.

BackgroundTumor spread through air spaces (STAS) is a novel pathologic characteristic in lung adenocarcinomas that indicates invasive tumor behavior. We aimed to explore the relationship between Twist, Slug and STAS in lung adenocarcinoma and to investigate the potential relationship between epithelial‐mesenchymal transition (EMT) and STAS.Materials and methodsOur study retrospectively analyzed 115 patients with resected lung adenocarcinomas to evaluate the relationship between Twist, Slug and STAS. STAS was diagnosed using hematoxylin‐eosin (H&E) staining. Immunohistochemistry was used to evaluate the expression levels of Slug and Twist.ResultsIn this study, 56 (48.7%) patients had STAS, 40 (34.8%) patients had Slug overexpression, and 28 (24.3%) patients had Twist overexpression. Patients with either STAS or Slug and Twist overexpression experienced poor recurrence‐free survival (RFS) and overall survival (OS). There were significant associations between Twist overexpression, Slug overexpression and the presence of STAS. The logistic model further revealed that pathological stage, Twist overexpression and Slug overexpression were independent risk factors for STAS. A multivariate analysis that contained Twist, Slug, pathologic stage and STAS, showed that pathologic stage and STAS were independent prognostic factors for poor RFS and OS. Another multivariate model that contained Twist, Slug and pathologic stage, showed that pathologic stage, Twist overexpression and Slug overexpression were independent risk factors for poor RFS and OS. In the cohort with STAS, the multivariate analysis showed that pathologic stage and Twist overexpression were independent risk factors for poor survival. The subgroup analysis showed that patients with both Slug overexpression and Twist overexpression with STAS received a poor prognosis.ConclusionsSTAS, Slug and Twist were correlated with poor RFS and OS in resected lung adenocarcinomas. Additionally, STAS was correlated with the overexpression of Twist and Slug, which could potentially provide information on the mechanism of STAS.

Survival in Mycosis Fungoides and Sezary Syndrome: How Can We Predict Outcome?

Early-stage mycosis fungoides (MF) has been associated with long survival. A recent meta-analysis including 6,279 patients with MF and Sezary syndrome found that about 10-20% of stage IB patients don't survive 5 years, whereas patients with advanced-stage MF and Sezary syndrome have a 5-year survival chance of about 20-60%. Identifying prognostic markers to better identify those at risk of limited survival may allow improved management choices and this, coupled with newer treatments, could improve survival.

The ABO Blood Group Impacts the Survival of Patients Undergoing Pancreatoduodenectomy for Biliary Tract Cancer.

Although ABO blood group has been reported to be associated with the outcome of patients with pancreatic cancer, little is known about its impact on patients with biliary tract cancer (BTC). We evaluated the prognostic relevance of ABO blood group in patients who had undergone resection of BTC. A total of 154 patients with BTC undergoing pancreatoduodenectomy were retrospectively reviewed. Associations between ABO blood group and patient survival were evaluated by univariate and multivariate analysis. The 5-year overall survival rate was higher in group O patients (n=46) than in other blood group patients (n=108) (65.8% vs. 47%, p=0.005). Multivariate analysis revealed that a non-O blood group was an independent risk factor for poor survival (p=0.021). ABO blood group is associated with the prognosis of patients with resected BTC; group O patients have a better outcome.

What are predictors of long-term survival after distal pancreatectomy for pancreatic adenocarcinoma? A single-center experience

Background: Few studies have previously explored potential predictors of long-term survival after distal pancreatectomy (DP) for pancreatic adenocarcinoma (PDAC), but reached conflicting Results. Furthermore, it appears that there are some differences of prognostic factors between the pancreatic head and body/ tail cancers. The present study aims to explore potential predictors of survival after DP for PDAC of the body and tail, in a relatively large single-center experience. Material & Methods: Between January 1, 2002, and December 31, 2015, 99 patients underwent DP for PDAC. Uni- and multivariate analyses were performed using the Kaplan-Meier curves with log-rank test and Cox proportional hazards models. Results: The median overall survival time for the entire cohort was 17.5 months. Upper digestive stenosis (HR = 1.762; 95%CI, 1.013 – 3.066; p = 0.045), weight loss (HR = 3.996; 95%CI, 1.055 – 15.127; p = 0.041), vascular resection (HR = 3.152; 95%CI, 1.322 – 7.514; p = 0.010), lymph nodes metastases (HR = 1.778; 95%CI, 1.018 – 3.106; p = 0.043), and positive resection margins (HR = 2.319; 95%CI, 1.296 – 4.151; p = 0.005) were found to be independent risk factors of poor survival. Conclusions: Patients with PDAC and weight loss, upper digestive stenosis at diagnosis, associated vascular resection, positive lymph nodes, and resection margins are expected to have a poor long-term survival after DP.

Identification of a novel CpG methylation signature to predict prognosis in lung squamous cell carcinoma.

DNA methylation plays a vital role in modulating genomic function and warrants evaluation as a biomarker for the diagnosis and treatment of lung squamous cell carcinoma (LUSC). In this study, we aimed to identify effective potential biomarkers for predicting prognosis and drug sensitivity in LUSC. A univariate Cox proportional hazards regression analysis, a random survival forests-variable hunting (RSFVH) algorithm, and a multivariate Cox regression analysis were adopted to analyze the methylation profile of patients with LUSC included in public databases: The Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO). A methylated region consisting of 3 sites (cg06675147, cg07064331, cg20429172) was selected. Patients were divided into a high-risk group and a low-risk group in the training dataset. High-risk patients had shorter overall survival (OS) (hazard ratio [HR]: 2.72, 95% confidence interval [CI]: 1.82-4.07, P< 0.001) compared with low-risk patients. The accuracy of the prognostic signature was validated in the test and validation cohorts (TCGA, n= 94; GSE56044, n= 23). Gene set variation analysis (GSVA) showed that activity in the cell cycle/mitotic, ERBB, and ERK/MAPK pathways was higher in the high-risk compared with the low-risk group, which may lead to differences in OS.Interestingly, we observed that patients in the high-risk group were more sensitive to gemcitabine and docetaxel than the low-risk group, which is consistent with results of the GSVA. We report novel methylation sites that could be used as powerful tools for predicting risk factors for poorer survival in patients with LUSC.

Short-term and long-term outcomes of oesophagogastric surgery for cancer in obese and normal weight patients.

Obesity is generally considered to be associated with worse surgical outcome and impaired oncological prognosis. The impact of pre-therapeutic body mass index (BMI) in patients with oesophagogastric cancer on the surgical outcome is controversially discussed. We retrospectively examined 730 patients who had undergone curative treatment for oesophagogastric cancer at the Medical Center of the University of Freiburg (1996-2015). Patients were divided in groups according to pre-therapeutic BMI (underweight (UW): <18.5 kg/m2 ; normal weight (NW): 18.5-25 kg/m2 ; overweight (OW): 25-30 kg/m2 ; and obese (OB): >30 kg/m2 ). Median BMI was 24.7 kg/m2 . Forty-two patients were UW, 337 NW, 263 OW and 84 OB. No significant differences between the groups (UW/NW/OW/OB) in operating time, hospital stay, perioperative complication rate and in-hospital mortality were found. Pre-therapeutic BMI was significantly associated with 5-year survival (UW: 22%, NW: 37%, OW: 51%, OB: 50%, P < 0.001). Multivariate analysis identified UW/NW (BMI <25 kg/m2 ) as an independent risk factor for poor survival (relative risk 1.38, P = 0.001) among high American Society of Anesthesiologists score, old age, positive resection margin and high cancer stage according to the Union Internationale Contre le Cancer (UICC). In oesophagogastric cancer, OW and OB patients can be treated surgically without impaired perioperative outcome and expect improved long-term survival compared to patients with a BMI <25 kg/m2 .

Clinical Value of lncRNA LUCAT1 Expression in Liver Cancer and its Potential Pathways.

Emerging studies indicate that long noncoding RNAs (lncRNAs) play a role as prognostic markers in many cancers, including liver cancer. Here, we focused on the lncRNA lung cancer-associated transcript 1 (LUCAT1) for liver cancer prognosis. RNA-seq and phenotype data were downloaded from the Cancer Genome Atlas (TCGA). Chisquare tests were used to evaluate the correlations between LUCAT1 expression and clinical features. Survival analysis and Cox regression analysis were used to compare different LUCAT1 expression groups (optimal cutoff value determined by ROC). The log-rank test was used to calculate the p-value of the Kaplan-Meier curves. A ROC curve was used to evaluate the diagnostic value. Gene Set Enrichment Analysis (GSEA) was performed, and competing endogenous RNA (ceRNA) networks were constructed to explore the potential mechanism. Data mining of the TCGA -Liver Hepatocellular Carcinoma (LIHC) RNA-seq data of 371 patients showed the overexpression of LUCAT1 in cancerous tissue. High LUCAT1 expression was associated with age (p=0.007), histologic grade (p=0.009), T classification (p=0.022), and survival status (p=0.002). High LUCAT1 patients had a poorer overall survival and relapse-free survival than low LUCAT1 patients. Multivariate analysis identified LUCAT1 as an independent risk factor for poor survival. The ROC curve indicated modest diagnostic performance. GSEA revealed the related signaling pathways, and the ceRNA network uncovered the underlying mechanism. High LUCAT1 expression is an independent prognostic factor for liver cancer.

Reappraisal of the validity of surgery for patients with pancreatic cancer aged 80 years or older stratified by resectability status.

The aim of this study was to assess the validity of surgical resection for patients with pancreatic ductaladenocarcinoma (PDAC) aged≥80years stratified by resectability status. Medical records of 245 patientswith resectable (R) and 169 with borderline resectable/unresectable (BR/UR) PDAC were reviewed retrospectively. Of the total of 414 patients, 56 (14%) were≥80years. The prognostic impact of age≥80years was analyzed with stratification by resectability status. No significant difference was found in the incidence of major complications between patients aged≥80 versus<80years (12% vs. 16% respectively; P=0.53). However, patients aged≥80years were significantly less likely to receive adjuvant gemcitabine+S-1 chemotherapy than those<80years (39% vs. 83%, respectively; P<0.001). Multivariate analyses identified age≥80years as an independent risk factor for poor survival in the BR/UR group (P=0.01), whereas it did not affect survival in the R group. Patients aged≥80years had a similar prognosis to<80years in R PDAC, whereas they had significantly worse prognosis in BR/UR PDAC. These findings suggest that surgical resection for patients with PDAC aged≥80years is validated in R PDAC, whereas its survival benefit might be limited in BR/UR PDAC.

Risk Factors for Poor Survival in Metastatic Castration-resistant Prostate Cancer Treated With Cabazitaxel in Japan

Cabazitaxel (CBZ) is approved for docetaxel-resistant castration-resistant prostate cancer (CRPC). This retrospective study aimed at assessing the efficacy and prognostic markers of cabazitaxel treatment in Japanese CRPC patients. The medical records of 44 consecutive Japanese patients with CRPC who started cabazitaxel at our Institution between January 2011 and February 2019 were reviewed and statistically analysed. The median follow-up period after cabazitaxel initiation was 13.2 [interquartile range (IQR)=6.9-21.5] months. The objective response rate, median progression-free survival period, and median overall survival period (OS) were 45.5%, 4.3 months, and 20.7 months, respectively. On multivariate analysis, higher prostate-specific antigen (PSA; >100 ng/ml), lower haemoglobin (<10 g/dl), and lower number of prior docetaxel therapy cycles (<10) were predictors for shorter OS. Patients with anemia, high PSA, and lower number of docetaxel therapy cycles might have shorter survival period from introduction of cabazitaxel therapy. In addition, PSA decline might still be a useful indicator as a predictor of prognosis of the metastatic CRPC patients treated with cabazitaxel.

The ALBI Grade is a Good Predictive Model for Very Late Recurrence in Patients with Hepatocellular Carcinoma Undergoing Primary Resection.

Hepatocellular carcinoma (HCC) patients still have risk for very late recurrence after curative resection. This study assesses prognostic factors in HCC patients with recurrence-free survival (RFS) for 5 years after primary resection. We enrolled 383 HCC patients who received primary tumor resection and achieved more than 5 years without recurrence after resection between January 2001 and April 2013. Predictive factors, including albumin-bilirubin (ALBI) grade, for RFS and overall survival (OS) were analyzed. After a median follow-up of 103 months, 57 patients (14.9%) had recurrent HCC, and 14 (3.7%) died. Independent predictors for HCC recurrence were male sex (p = 0.035), pre-operative liver cirrhosis (LC) (p = 0.025), serum creatinine >1.5 mg/dL (p = 0.045), post-operative 5th-year alpha-fetoprotein (AFP) > 15 ng/ml (p < 0.001), LC (p = 0.004), and ALBI grades 2 and 3 (p < 0.001). I ndependent risk factors for poor survival were age >70years (p = 0.002), post-operative 5th-year AFP >15 ng/ml (p = 0.003), and ALBI grades 2 and 3 (p = 0.002). Patients whose deteriorated ALBI grades 5 years after resection had adverse RFS outcomes compared to those with constant (p = 0.056) and improved ALBI grades (p = 0.008). In subgroup analysis, patients with post-operative 5th-year ALBI grades 2 and 3 had significantly poorer RFS and OS (both p < 0.001) than those with grade 1 among patients with low post-operative 5th-year AFP (<15 ng/mL). In HCC patients without recurrence for 5 years after curative resection, post-operative 5th-year ALBI grade is useful for predicting outcomes, even with low AFP during follow-up.

Tumor microRNA-126 controls cell viability and associates with poor survival in patients with esophageal adenocarcinoma.

Esophageal adenocarcinoma displays a poor prognosis and current treatments are often not curative. Pathological TNM-stage is a prognostic parameter, but a better understanding of the pathophysiology of esophageal adenocarcinoma is needed to better predict survival. Recent work in other malignancies indicated an important role for the regulator microRNA-126 (miR-126) in tumors. The aim of this study was to investigate the function of miR-126 in esophageal adenocarcinoma and to correlate expression of miR-126 with tumor cell behavior and patient survival. Functional assays were performed in esophageal adenocarcinoma cell lines (OE33) in vitro by overexpressing or antagonizing miR-126 and assessing cellular processes linked to the hallmarks of cancer. In vivo pre-treatment biopsies of 58 patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiotherapy and surgery were analyzed for miR-126 expression in tumor cells by qRT-PCR and patient survival was analyzed by Kaplan–Meier and Cox regression. In OE33 cancer cells, stable overexpression of miR-126 modest though significantly altered expression of genes related to cell death (MEK1) and DNA repair (POLB and TERF1) was observed. Also the secretion of the angiogenic and pro-inflammatory factors, VEGF, IL-1β, and IL-6 were regulated by miR-126 ( P &lt; 0.029). Importantly, miR-126 was found to be a regulator of cell viability in OE33 cells. Overexpressing ( P = 0.043) and antagonizing ( P = 0.035) miR-126 showed reciprocal effects on tumor cell viability and significantly regulated expression of pro- and anti-apoptotic genes, TP53, and GATA6 ( P &lt; 0.031). In patients, high levels of miR-126 expression in pre-treatment tumors were significantly associated with poor survival ( P = 0.031). In multivariable analysis, high miR-126 ( P = 0.038) together with ypN-stage ( P = 0.048) were shown to be independent risk factors for poor survival. In conclusion, high expression of miR-126 in esophageal adenocarcinoma prevents tumor-cell death and is associated with poor patient survival. This study warrants further analysis of miR-126 as biomarker or potential therapeutic target for OAC. Impact statement Esophageal adenocarcinoma is a common form of cancer of the esophagus. It has an increasing health impact as it is associated with very poor patient survival. A better understanding of the pathophysiology of this cancer is needed to identify better treatment strategies and to provide a better prognosis for these patients. MicroRNAs have emerged as important molecular regulators of cancer cell viability and proliferation. The aim of our study was to investigate the role of one very well established microRNA, miR-126, in esophageal adenocarcinoma. Our research shows clear experimental evidence that miR-126 controls cell viability of esophageal adenocarcinoma cells. High (over)expression of miR-126 increased the viability of these cells. Our preclinical data were shown to be clinically relevant for this field of oncology. In an independent validation study of esophageal adenocarcinoma biopsies, we confirmed that high miR-126 expression in tumor cells was an independent risk factor for poor patient survival.

Soluble CXCL16 promotes TNF-α-induced apoptosis in DLBCL via the AMAD10-NF-κB regulatory feedback loop.

We had previously identified that the co-expression of transmembrane CXCL16 (TM-CXCL16) and itsreceptor CXCR6 is an independent risk factor for poor survival in patients with diffuse large B-cell lymphoma (DLBCL). However, the impact of the soluble form of CXCL16 (sCXCL16) on the pathogenesis of DLBCL remains unknown. In the present study, the synergistic effect of sCXCL16 and tumor necrosis factor α (TNF-α) on apoptosis in DLBCL cell lines (OCI-LY8 and OCI-LY10) was investigated in vitro. sCXCL16 reinforced TNF-α-mediated inhibition of DLBCL cell proliferation, as determined by the cell counting kit-8 assay. The results of annexin V staining showed that sCXCL16 enhanced TNF-α-induced apoptosis in OCI-LY8 and OCI-LY10 cells through a death receptor-caspase signaling pathway. The results of gene microarray suggested a significant upregulation of differentially expressed genes in the TNF signaling pathway. sCXCL16 increased the concentration of extracellular TNF-α by binding to CXCR6 to activate the nuclear factor-κB (NF-κB) signaling pathway. TNF-α also induced the secretion of sCXCL16 by increasing the expression of ADAM10, which is known to cleave TM-CXCL16 to yield sCXCL16. Moreover, bioinformatics analysis revealed that elevated TNF-α and ADAM10 expression levels in tumor tissues predicted better survival in patients with DLBCL. Thus, our study suggests that sCXCL16 enhances TNF-α-induced apoptosis of DLBCL cells, which may involve a positive feedback loop consisting of TNF-α, ADAM10, sCXCL16, and members of the NF-κB pathway. sCXCL16 and TNF-α may be used as prognostic markers in the clinic, and their combinational use is a promising approach in the context of DLBCL therapy.