Risk Factors For Late Recurrence Research Articles

Prediction of late recurrence after radiofrequency ablation of HBV-related hepatocellular carcinoma with the age-male-albumin-bilirubin-platelets (aMAP) risk score: a multicenter study.

Long-term survivals of patients with HBV-related hepatocellular carcinoma are limited by the high incidence of tumor recurrence after radiofrequency ablation (RFA), identification of the risk factors and understanding the patterns of recurrence can help to improve the comprehensive management of patients after RFA. Therefore, the purpose of the study is to explore the prognostic value of the age-male-albumin-bilirubin-platelets (aMAP) score in patients with early-stage HBV-related hepatocellular carcinoma (HCC) receiving RFA; investigate the risk factors and patterns of late recurrence (LR); and develop a nomogram to predict recurrence-free survival (RFS). A retrospective review of HBV-related HCC patients who underwent primary RFA from March 2012 to December 2020 was conducted. The prognostic value of the aMAP score was evaluated in a primary cohort (n=302) and then further validated in an independent validation cohort (n=143). The optimal threshold of aMAP scores was calculated by X-tile 3.6.1 software. A prognostic nomogram was constructed from multivariate analysis and validated in an external validation cohort. Patients with aMAP scores ≤63.8, 63.8-67.8, and >67.8 were classified into low-, medium-, and high-recurrence risk groups, respectively. The C-index to predict LR was 0.76 (95% CI: 0.700-0.810). The high-risk group was associated with the worst RFS (HR: 5.298; 95% CI, 2.697-10.408; P<0.001) and overall survival (OS) (HR: 2.639; 95% CI, 1.097-6.344; P=0.03) compared with medium- and low-risk groups. The aMAP score, multiple tumors and preoperative HBV DNA level were independent risk factors for LR. The proposed nomogram had excellent performance in predicting LR of HBV-related HCC [C-index: 0.82 (95% CI: 0.772-0.870)]. This study demonstrated that the aMAP score can serve as an objective predictor of LR for HBV-related HCC patients after RFA. The nomogram based on preoperative HBV DNA level, aMAP score, and number of tumors can reliably help clinicians to stratify the recurrence risk of HCC patients after RFA.

Left Atrial Appendage Circular RNAs Are New Predictors of Atrial Fibrillation Recurrence After Surgical Ablation in Valvular Atrial Fibrillation Patients

Atrial fibrillation (AF) recurrence after ablation will increase mortality and morbidity during follow up. We attempted to evaluate the relationship between circular RNAs (circRNA) and AF recurrence to establish a predictive model for early intervention. Patients who received surgical ablation retrospectively were analyzed. The expression of circRNAs were detected in the left atrial appendage. The independent risk factors of late recurrence were analyzed by multivariate analysis. The predictive model was visualized by Nomogram and tested by receiver operating characteristic curve and calibration plot. Kaplan-Meier plot was used to compare the rate of freedom from AF recurrence after surgery. The relationships between circRNAs and clinical characteristics were detected by Spearman's correlation analysis. A total of 136 patients were enrolled from September 2018 to June 2019, 55 patients experienced late recurrence during one-year follow up. Increased age, longer AF duration and increased circ 81906-RYR2, circ 44782-LAMA2, circ 418-KCNN2 and circ 35880-ANO5 were detected in recurrent patients. Multivariate analysis revealed that increased age (odds ratio (OR)=1.072, P = 0.006), longer AF duration (OR=1.007, P = 0.036) and increased circ 81906-RYR2 (OR=2.210, P < 0.001) were independent risk factors for late recurrence. Area under the curve was 0.77, and the cut-off value was 70 points of the predictive model. Kaplan-Meier plots showed that patients over 70 points tended to experience AF recurrence. Circ 81906-RYR2 could be a new predictor of late recurrence after surgical ablation. A predictive model consists of age, atrial fibrillation duration, and circ 81906-RYR2 was alternative for early intervention of AF recurrence.

Early Recurrence Is Reliable Predictor of Late Recurrence After Radiofrequency Catheter Ablation of Atrial Fibrillation

This study aimed to compare the risk of late recurrence in patients with and without early recurrence. Early recurrence of atrial fibrillation (AF) or atrial tachycardia (AT) after radiofrequency catheter ablation (RFCA) in AF patients is known to be a transient phenomenon. The theoretical basis of the blanking period is based on such observations. However, the clinical implications of early recurrence need further validation. Consecutive RFCA cases in a tertiary hospital were analyzed. Early recurrence was defined as any AT or AF event occurring within 90-days post-RFCA. Early recurrence as AT and AF were also analyzed separately. A total of 3,120 patients underwent RFCA. Early recurrence occurred in 751 patients (24.1%). Patients who experienced early recurrence had a larger left atrium, worse hemodynamics in the left atrial appendage, and a higher prevalence of nonparoxysmal AF and heart failure. Among patients who experienced early recurrence, 69.6% of patients eventually had late recurrence. Early recurrence was associated with a 4.3- and 3.6-fold increase in the risk of late recurrence after single and multiple procedures, respectively. After multivariate adjustment, early recurrence was an independent risk factor for late recurrence with 3.6- and 2.8-fold increase in the risk of late recurrence after single and multiple procedures, respectively. Early recurrence AT had a lower risk of late recurrence compared with early recurrenceAF. Early recurrence was a reliable predictor for late recurrence. The clinical significance of the blanking period in the current guidelines may need to be revisited.

Risk factors for early and late recurrence in hepatocellular carcinoma after liver transplantation

Background: Risk factors of early and late recurrence in hepatocellular carcinoma (HCC) after liver transplantation (LT) remain unclear. Aim: To identify factors that affect, both early and late recurrence in this setting. Methods: We retrospectively analyzed outcomes of 220 patients with HCC who received LT. Two patients who underwent re-transplantation were excluded. Early, late, and very late recurrence were defined as recurrence in the 1st year, 1–5 years, and >5 years after LT, respectively. Kaplan–Meier survival curves were generated, and log-rank tests were performed to compare survival between these groups. Univariate and multivariate Cox proportional-hazard models for risks of early and late recurrence were established. Results: Twenty and 19 patients experienced HCC recurrence in the 1st year and between 1 and 5 years, respectively, after undergoing LT. The groups differed significantly in cumulative postrecurrence survival rate. The hazard ratio of early recurrence for tumor size >3 cm was 1.766 (P = 0.046) and that for tumor number >3 was 1.929 (P = 0.027). Alpha-fetoprotein >20 ng/mL was a predictor of early recurrence in multivariate analysis (P = 0.077). The hazard ratio of late recurrence for HCC with microvascular invasion was 1.891 (P = 0.047). Conclusion: The recurrence rate of HCC was high in the 1st year after LT. Patients with early recurrence had a poorer survival rate than those with late recurrence. Tumor size >3 cm and tumor number >3 were risk factors of early recurrence. Microvascular invasion was a risk factor for late recurrence. Close individual surveillance is needed in patients with these risk factors.

Late recurrence of hepatocellular carcinoma after radiofrequency ablation: a multicenter study of risk factors, patterns, and survival.

This study aims to determine the risk factors, patterns, and long-term survival outcomes of late recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) within the Milan criteria and develop a nomogram to predict the recurrence-free survival (RFS). This retrospective study included patients with HCC within the Milan criteria, who received RFA at three hospitals in China from January 2011 to December 2016. The clinical variables were assessed by univariate and multivariate Cox regression analyses. A total of 398 patients were included. The median follow-up was 58.7months (range: 24.1-96.0). Ninety-eight patients had late recurrence. Furthermore, 14 patients (14.29%) had local tumor progression (LTP) alone, 43 patients (43.88%) had intrahepatic distant recurrence (IDR) alone, 15 patients (15.31%) had extrahepatic recurrence (ER) alone, three patients (3.06%) had both LTP and IDR, six patients (6.12%) had both LTP and ER, and 17 patients (17.35%) had both IDR and ER. Patients without late recurrence had better long-term overall survival (OS) compared to those with late recurrence (p < 0.001). Male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence. A well-discriminated and calibrated nomogram was constructed to predict the probability of RFS. Male gender, multiple tumors, and cirrhosis are the independent risk factors of late recurrence after RFA for HCC within the Milan criteria. Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. An individualized surveillance and prevention strategy for HCC patients after RFA should be developed. • In the present retrospective study of 398 patients, male gender, multiple tumors, and cirrhosis were the independent risk factors of late recurrence (> 2years) of HCC after RFA. • The most common pattern of late recurrence was intrahepatic distant recurrence alone (n = 43, 43.88%). Late recurrence might mainly occur from de novo HCC under the background of cirrhosis. • A prognostic nomogram was built to predict the individualized recurrence-free survival after RFA, which achieved good calibration and discriminatory ability with a concordance index of 0.763.

Re-definition of blanking period in radiofrequency catheter ablation of atrial fibrillation in the contact force era.

Early recurrence (ER) of atrial fibrillation (AF) is defined as the recurrence of atrial tachyarrhythmias within 3 months after AF ablation, however, this definition is based on data from the era of radiofrequency catheter ablation (RFCA), without contact force (CF) technology. We investigated the significance of ER as a risk factor for late recurrence (LR) in paroxysmal AF (PAF) patients treated with CF and non-CF-guided ablation. We studied 395 patients with PAF who underwent RFCA. Of these, 97 patients underwent RFCA without-CF technology (non-CF group) and 298 underwent with CF technology (CF group). Over a 2-year postablation follow-up period, LR occurred in 54 (55.7%) patients in the non-CF group, and in 105 (35.2%) patients in the CF group. ER had a more significant relationship with LR in the CF group, and all patients in the CF group with ER in the third month developed LR. PAF patients with ER who have undergone CF-guided ablation have a greater risk of LR than those who have undergone non-CF-guided ablation. ER in the third month after CF-guided ablation may indicate an absolute risk of LR. Blanking period could be defined as 2 months in the CF era.

Novel Prognostic Nomograms for Predicting Early and Late Recurrence of Hepatocellular Carcinoma After Curative Hepatectomy.

AimHepatectomy is the main curative method for patients with hepatocellular carcinoma (HCC) in China. Unfortunately, high recurrence rate after hepatectomy poses negative impact on the prognosis of patients. This study aimed to develop prognostic nomograms to predict early recurrence (ER) and late recurrence (LR) of HCC after curative hepatectomy.Patients and MethodsTotal of 318 HCC patients undergoing curative hepatectomy from January 2012 to January 2018 were retrospectively recruited. Potential risk factors that were significant for predicting ER and LR in univariate analysis were selected for multivariate survival model analysis using the backward stepwise method. Risk factors identified in multivariate analysis were used to develop nomograms to predict ER and LR. The nomogram was internally validated using 2,000 bootstrap samples from 75% of the original data.ResultsAmong 318 patients, 164 showed postoperative recurrence, of which 140 and 24 had ER (≤2 years) and LR (>2 years), respectively. Multivariate analysis showed that age, Hong Kong Liver Cancer Stage, albumin-bilirubin, METAVIR fibrosis grade, and microvascular invasion were risk factors of ER for HCC after curative hepatectomy. The AUC of the ROC curve for ER in the development set (D-set) was 0.888 while that in the validation set (V-set) was 0.812. Neutrophil/lymphocyte ratio and glypican-3 (+) were risk factors for LR in HCC patients after curative hepatectomy. The AUC of the ROC curve for LR predictive nomogram that integrated all independent predictors was 0.831. The AUC of the ROC curve for LR in the D-set was 0.833, while that for LR in the V-set was 0.733. The C-index and AUC of ROC for the proposed nomograms were more satisfactory than three conventional HCC staging systems used in this study.ConclusionWe developed novel nomograms to predict ER and LR of HCC patients after curative hepatectomy for clinical use to individualize follow-up and therapeutic strategies.

Risk factors for recurrence of paroxysmal atrial fibrillation after second-generation of cryoballoon ablation.

To analyze the risk factors for recurrence of paroxysmal atrial fibrillation (PAF) after the second-generation of cryoballoon ablation (CBA). A total of 67 patients with PAF, who underwent CBA treatment from March 2017 to June 2018, were selected from the Department of Cardiology, Second Xiangya Hospital of Central South University. The incidence rate of early recurrence (within 3 months) and late recurrence (after 3 months) in patients with PAF were analyzed retrospectively and the risk factors for recurrence were discussed. Among the 67 patients, 40 were males (59.7%). The patients were at 34-84 (58.91±10.49) years old and followed up for 4-15 (9.04±4.66) months. Fifteen (22.4%) patients suffered early recurrence, and 16 (23.9%) patients suffered late recurrence. Among the 16 patients with late recurrence, 12 suffered early recurrence. The results of univariate analysis showed that there were significant differences between the early recurrence group and the non-early recurrence group in the freezing temperature of right inferior pulmonary vein at 30 s and right superior pulmonary vein at 60 s, the nadir freezing temperature of right inferior pulmonary vein and the width of left inferior pulmonary vein (all P<0.05); there were significant differences between the late recurrence group and the non-late recurrence group in the left atrial diameter, early recurrence and the nadir temperature of left superior pulmonary vein (all P<0.05). Multivariate analysis found that the freezing temperature of right superior pulmonary vein at 60 s was an independent risk factor for early recurrence (OR=1.108, 95% CI 1.002 to 1.225, P=0.046); and early recurrence was an independent risk factor for late recurrence (OR=24.94, 95% CI 7.85 to 41.91, P=0.020). Freezing temperature of right superior pulmonary vein at 60 s is an independent risk factor of early recurrence, and early recurrence is an independent risk factor of late recurrence after the second-generation cryoballon ablation for PAF.

Hepatobiliary phase hypointense nodule without arterial phase hyperenhancement as a risk factor for late recurrence (>1 year) of hepatocellular carcinoma after surgery

To evaluate the value of magnetic resonance imaging (MRI) features, including liver stiffness measured by magnetic resonance elastography (MRE) and the presence of hepatobiliary phase (HBP) hypointense nodule without arterial phase hyperenhancement (APHE), for predicting late recurrence (>1 year) after surgery for hepatocellular carcinoma (HCC). This retrospective study included 124 consecutive patients who had undergone surgery for HCC and preoperative MRI. After excluding patients with early recurrence within 1 year after surgery, 89 patients were analysed. Preoperative MRI images were reviewed by a radiologist to record imaging findings, including (1) liver stiffness by MRE, (2) size of the HCCs, (3) number of HCCs, and (4) presence of HBP hypointense nodule without APHE. Pathological findings included tumour grade, vascular/biliary/capsule invasion, and fibrosis stage of the liver. Considering imaging/pathological findings and patients' characteristics as dependent variables, Cox proportional hazards model analysis was performed to identify independent factors associated with late recurrence after surgery. The median follow-up period was 37.3 months. During follow-up, 29 patients (32.5%) developed late recurrence after surgery. In multivariate analysis, underlying liver disease (viral hepatitis) and presence of HBP hypointense nodules without APHE (p=0.010 and 0.033, respectively) were independently associated with disease-free survival (DFS). Kaplan-Meier analysis revealed that patients with HBP hypointense nodules without APHE had a significantly lower DFS rate than those without the nodule (39.2% versus 74.1% at 3 years after surgery, p=0.008). The presence of HBP hypointense nodules without APHE was an indicator of late recurrence after surgery for HCC.

Prognostic Value of DEPDC1 Expression in Tumor and Non-tumor Tissue of Patients With Hepatocellular Carcinoma.

To evaluate the impact of DEPDC1 expression on patient prognosis after hepatic resection for hepatocellular carcinoma (HCC). We reviewed data from 75 patients who underwent hepatic resection for HCC between 2004 and 2013. Recurrence at 2 years following resection, which mainly included metastatic recurrence, was defined as late recurrence. DEPDC1 was up-regulated in HCC tissue and in non-tumor tissue of patients with HCC compared to normal liver (p<0.01 and p<0.01, respectively). High expression of DEPDC1 was associated with poor overall, disease-specific, and disease-free survival (p=0.02, p<0.01, and p<0.01, respectively). High DEPDC1 expression was an independent predictor of death and recurrence (p=0.03 and p<0.01, respectively). High expression of DEPDC1 in non-tumor liver was an independent risk factor for late recurrence (p=0.04). High expression of DEPDC1 in tumor tissue appears to be associated with tumor progression and poor prognosis.

Prediction of late recurrence in patients with breast cancer: elevated neutrophil to lymphocyte ratio (NLR) at 5years after diagnosis and late recurrence.

Late recurrence accounts for nearly half of the recurrences in estrogen receptor (ER)-positive breast cancer and decreases post-recurrence survival in patients with ER-negative breast cancer. Clinicopathological factors and multigene assays have been used for various purposes but their prognostic capacity for late recurrence was limited. This study aimed to determine whether neutrophil to lymphocyte ratio (NLR) taken after primary treatment can be a feasible prognostic factor for late recurrence. Patients who were diagnosed with primary breast cancer and completed planned treatment were enrolled; data were retrospectively collected from the Wonju Severance Hospital database of Yonsei University. 496 patients completed planned treatment for their primary breast cancer. 385 were disease free after 5years of the primary diagnosis and 330 were enrolled for second-look NLR analysis. NLR analysis performed approximately 5years after the primary diagnosis categorized patients into high and low risk of late recurrence with p < 0.001 and an elevated NLR was found as an independent risk factor for late recurrence (HR 1.448, CI 1.168-1.795, p < 0.001). A clinically valid biomarker to determine late recurrence is urgently needed to prevent patients from treatment extension with little benefit. Elevated NLR is found as an independent prognostic factor for late recurrence and could be utilized as a reliable, easily accessible, and cost-effective test.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load.

A retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. A total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. The median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 IU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 IU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032). HBsAg > 250 IU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.

Radiofrequency catheter ablation for paroxysmal atrial fibrillation: outcomes during a 3-year follow-up period.

ObjectiveThis study was performed to observe the effect of radiofrequency catheter ablation (RFCA) in patients with paroxysmal atrial fibrillation (PAF) and to explore the risk factors for late recurrence of atrial fibrillation (LRAF) after a single RFCA session.MethodsIn this retrospective study, 243 patients with PAF underwent RFCA and were followed up regularly.ResultsAt a median follow-up of 37 months after a single procedure, 60.5% of patients maintained sinus rhythm (SR), and at a median follow-up of 42 months after multiple procedures, 74.9% of patients maintained SR. The statistically significant risk factors for LRAF after a single RFCA session were the left atrial diameter (LAD), left inferior pulmonary vein superior–inferior diameter (LIPV SID), PV number variation, circumferential pulmonary vein isolation (CPVI) combined with additional ablation, and early recurrence of atrial fibrillation (ERAF). The best cut-off value for LAD was 35.5 mm.ConclusionsDuring a 3-year follow-up, about 70% of the patients with PAF maintained SR. LRAF after a single procedure was associated with the LAD, LIPV SID, PV number variation, CPVI combined with additional ablation, and ERAF.

Risk Factors, Patterns, and Outcomes of Late Recurrence After Liver Resection for Hepatocellular Carcinoma

Late recurrence (more than 2 years) after liver resection for hepatocellular carcinoma (HCC) is generally considered as a multicentric tumor or a de novo cancer. To investigate the risk factors, patterns, and outcomes of late recurrence after curative liver resection for HCC. This study was a multicenter retrospective analysis of patients who underwent curative liver resection for HCC at 6 hospitals in China from January 2001 to December 2015. Among 734 patients who were alive and free of recurrence at 2 years after resection, 303 patients developed late recurrence. Data were analyzed from June 2017 to February 2018. Liver resection for HCC. Risk factors of late recurrence as well as patterns, treatments, and long-term outcomes of patients with late recurrence. Univariate and multivariate Cox regression analyses were performed to identify independent risk factors of late recurrence. Of the included 734 patients, 652 (88.8%) were male, and the mean (SD) age was 51.0 (10.3) years. At a median (interquartile range) follow-up of 78.0 (52.8-112.5) months, 303 patients (41.3%) developed late recurrence. Multivariate analysis revealed that male sex, cirrhosis, multiple tumors, satellite nodules, tumor size greater than 5 cm, and macroscopic and microscopic vascular invasion were independent risk factors of late recurrence. Of the 303 patients with late recurrence, 273 (90.1%) had only intrahepatic recurrence, 30 (9.9%) had both intrahepatic and extrahepatic recurrence, and none had only extrahepatic recurrence. Potentially curative treatments were given to 165 of 303 patients (54.5%) with late recurrence, which included reresection, transplant, and local ablation. Multivariate Cox regression analysis showed that regular surveillance for postoperative recurrence (hazard ratio [HR], 0.470; 95% CI, 0.310-0.713; P = .001), cirrhosis (HR, 1.381; 95% CI, 1.049-1.854; P = .02), portal hypertension (HR, 2.424; 95% CI, 1.644-3.574; P < .001), Child-Pugh grade of B or C (HR, 1.376; 95% CI, 1.153-1.674; P < .001), Barcelona Clinic Liver Cancer stage B (HR, 1.304; 95% CI, 1.007-1.708; P = .04) and stage C (HR, 2.037; 95% CI, 1.583-2.842; P < .001), and potentially curative treatment (HR, 0.443; 95% CI, 0.297-0.661; P < .001) were independent predictors of overall survival for patients with late recurrence. Late recurrence after HCC resection was associated with sex, cirrhosis, and several aggressive tumor characteristics of the initial HCC. The patterns of late recurrence suggested surveillance for recurrence after 2 years of surgery should be targeted to the liver. Postoperative surveillance improved the chance of potentially curative treatments, with improved survival outcomes in patients with late recurrence.

Adjuvant transarterial chemoembolization to improve the prognosis of hepatocellular carcinoma following curative resection.

The present study aimed to investigate the prognostic factors for recurrence of hepatocellular carcinoma (HCC) following curative resection, and evaluate the efficacy of postoperative adjuvant transarterial chemoembolization (TACE) in improving prognosis. A total of 166 patients who underwent curative resection followed by adjuvant TACE, and 190 patients who underwent curative resection alone were studied retrospectively. Univariate and multivariate analyses were performed to investigate the risk factors of recurrence. Separated based on risk factors, subgroup studies were conducted and the association between TACE and recurrence rates was examined. Postoperative overall survival rates were determined using the Kaplan-Meier method and differences between the two therapeutic strategies were identified through log-rank analysis. Computerized tomography (CT)/magnetic resonance imaging (MRI) images were used to evaluate the function of postoperative adjuvant TACE for enhancing the efficacy of CT/MRI in detecting recurrence. The results of the univariate and multivariate analyses revealed that tumor capsule invasion, vascular invasion, and multiple nodules were risk factors of early recurrence. For patients with these risk factors, recurrence rates were markedly decreased at 6 and 12 months, but not at 18 and 24 months, if TACE was added to curative resection. The hepatitis B virus (HBV) was a risk factor for late recurrence. Postoperative TACE was not effective in reducing the recurrence rate in patients with HBV. Survival increased following curative resection with TACE compared with curative resection alone. Furthermore, adjuvant TACE enhanced the efficacy of CT/MRI in detecting recurrence. Postoperative adjuvant TACE may improve the prognosis of HCC following curative resection.

Is Long-Term Follow-Up Mandatory for Stage I Oral Tongue Cancer?

The objective of this study was to analyze the outcomes and possible risk factors for late recurrence of pathologic stage I oral tongue squamous cell carcinomas (SCCs) in patients considered disease free at 3years. This retrospective study evaluated all patients with pathologic stage I oral tongue cancer within a tertiary care center from 2003 through 2013 who had been followed for a minimum of 36months. One hundred twelve patients met inclusion criteria for long-term analysis. Despite the high overall survival of 92.2% for true pT1N0M0 disease, initial surgery failed in 25 of 112 patients (22.3%) who developed late disease recurrence (>36-month follow-up) locally (19.6%; n=22), regionally (4.4%; n=5), or as second primary disease (11.6%; n=13). Eleven patients (50%) who had local recurrence could be salvaged with a second surgery, requiring no further treatment (mean, 48.7months). Projected 10-year disease-free survival and overall survival were 61 and 89%, respectively. Thirty-three percent (n=3 of 9) of deaths occurred in long-term patients considered disease free at 36months. Stage I tongue SCC is more common in women and is associated with pre-existing leukoplakia. Although overall survival is excellent, a high failure rate from local recurrence or a new second primary is seen over an extended period. Long-term follow-up is mandatory because local salvage rates are excellent if SCC is diagnosed early. Regional failure carries a poor prognosis.

Correlation between postoperative neutrophil to lymphocyte ratio and recurrence and prognosis of hepatocellular carcinoma after radical liver resection

Objective: To investigate the correlation between postoperative peripheral blood neutrophil to lymphocyte ratio (NLR) and recurrence and prognosis of patients with hepatocellular carcinoma (HCC). Methods: The clinicopathological and follow-up data of 344 patients with HCC who underwent radical liver resection from May 2010 to April 2014 were analyzed retrospectively. Results: Of the 344 patients, 104 had early recurrence and 84 had late recurrence. Receiver operating characteristic (ROC) curve analysis showed that the NLR predicted area under the curve (AUC) of early recurrence was 0.622 (P<0.001), the optimal cut-off value was 2.41. The AUC of late recurrence was 0.634 (P=0.001), the optimal cut-off value was 2.15. Cox multivariate analysis showed the serum concentration of hepatitis B surface antigen (HR=2.508, 95% CI: 1.311-4.798), microvascular invasion (HR=2.422, 95% CI: 1.239-4.734), Milan criteria (HR=2.373, 95% CI: 1.427-3.948) and postoperative NLR (HR=2.285, 95% CI: 1.379-3.788) were independent risk factors of early recurrence after HCC resection. Postoperative NLR (HR=2.927, 95% CI: 1.630-5.255), liver cirrhosis (HR=2.531, 95% CI: 1.291-4.962) and serum concentration of albumin (HR=2.257, 95% CI: 1.251-4.073) were independent risk factors of late recurrence after HCC resection. The median recurrence-free survival (RFS) of the 344 patients was 45.0 months, and the median overall survival (OS) was 63.2 months. ROC curve analysis showed that the postoperative NLR predicted 5-year survival AUC was 0.689 (P<0.05), with an optimal cutoff of 2.29. Cox multivariate analysis showed microvascular invasion (HR=2.247, 95% CI: 1.534-3.291), postoperative NLR (HR=2.217, 95% CI: 1.653-2.974), and liver cirrhosis (HR=1.685, 95% CI: 1.168-2.431), Milan criteria (HR=1.679, 95% CI: 1.238-2.277), serum concentration of hepatitis B surface antigen (HR=1.623, 95% CI: 1.102-2.392), serum concentration of albumin (HR=1.43, 95% CI: 1.066-1.918) were independent factors of RFS after HCC resection, while microvascular invasion (HR=3.862, 95% CI: 2.407-6.197), Barcelona staging (HR=2.864, 95% CI: 1.600-5.125), postoperative NLR (HR=2.688, 95% CI: 1.782-4.055), liver cirrhosis (HR=2.039, 95% CI: 1.184-3.514), serum concentration of albumin (HR=1.81, 95% CI: 1.204-2.720) were independent factors of OS. Conclusions: For HCC patients who receive radical liver resection, postoperative NLR ≥2.29 implicates poor prognosis. Moreover, postoperative NLR ≥2.41 suggests early recurrence, while NLR ≥2.15 suggests late recurrence.

Clinicopathologic features of hormone-receptor-positive breast cancer patients with late recurrence.

The number of long-term breast cancer survivors with a risk of late recurrence is increasing. Hormone-receptor-positive patients have greater risks of late recurrence. Although several studies demonstrated that extended adjuvant endocrine therapy reduces the incidence of late recurrence, it remains unclear which hormone-receptor-positive patients have greater risks of late recurrence. Hormone-receptor-positive breast cancer patients were retrospectively selected from the prospective database of primary breast cancer patients treated at Keio University Hospital from January 1989 to December 2003. Late recurrence was defined as initial recurrence after 5 years from the initial surgery. We evaluated the clinicopathologic features of breast cancer patients with late recurrence. At a median follow-up of 10.9 years (range, 5.1-23.8), 371 patients had no recurrence, 90 had early recurrence (within 5 years), and 83 had late recurrence. Multivariate analysis revealed that >4 involved lymph nodes were significant risk factors for late recurrence (P < .001), whereas 1-3 positive nodes were not. Endocrine therapy significantly reduced the incidence of late recurrence (P < .001). After menopause, adjuvant therapy with aromatase inhibitors resulted in longer disease-free survival than tamoxifen (10-year disease-free survival: 97.6% vs 89.7%, P = .0955). High nodal involvement was significantly correlated with late recurrence in hormone-receptor-positive breast cancer patients. Hormone-receptor-positive breast cancer patients who receive adjuvant endocrine therapy with tamoxifen alone might be candidates for extended endocrine therapy.

ER-positive breast cancer patients with more than three positive nodes or grade 3 tumors are at high risk of late recurrence after 5-year adjuvant endocrine therapy.

PurposeCurrently, although several clinical trials available give strong suggestions that extension of endocrine therapy has benefits, the risk level at which patients may benefit from extended endocrine therapy remains uncertain. This study aimed to identify the proportion of patients at a substantial risk of late recurrence after 5-year adjuvant endocrine therapy.Patients and methodsWe reviewed 1,056 female patients with primary breast cancer who underwent curative resection between January 2006 and December 2011. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model to identify prognostic factors.ResultsA total of 327 eligible patients were eventually enrolled in this study. Among them, 42 (12.8%) patients suffered from distant metastasis and 34 (10.4%) patients experienced locoregional recurrence after 5-year adjuvant endocrine therapy. In multivariate analysis, patients with more than three positive nodes (hazard ratio [HR] =2.176, 95% CI=1.071–4.421; P=0.032) and histologic grade 3 disease (HR=2.098, 95% CI=1.300–3.385; P=0.002) were significantly associated with high risk of late recurrence. However, only histologic grade 3 (HR=2.212, 95% CI=1.166–4.194; P=0.015) was significantly associated with high risk of distant metastasis.ConclusionLate relapse after completion of 5-year adjuvant endocrine therapy was still common, and grade 3 and more than three positive nodes were the risk factors of late recurrence, while grade 3 was the only risk factor of late distant metastasis. These patients might benefit from extended endocrine therapy.

Risk Factors for Prognosis of Hepatocellular Carcinoma After Curative Resection In Patients with Low Hepatitis B Viral Load

BackgroundA retrospective cohort study was conducted to investigate the effect of hepatitis B surface antigen (HBsAg) level on prognosis in low viral load (< 2000 IU/mL) patients with hepatitis B-related hepatocellular carcinoma (HCC) after curative resection. Material and MethodsA total of 192 patients with low viral load who had received curative resection of pathologically confirmed HCC were analyzed to determine the factors affecting prognosis. The risk factors for survival, early and late recurrence (2 years as a cut-off) were studied. ResultsThe median follow-up time was 38.5 months. The overall survival rates at 1-, 3-, and 5-year after curative resection were 94.2%, 64.0%, and 45.2%, respectively. The cumulative recurrence rates at 1-, 3-, and 5-year after curative resection were 22.4%, 46.5%, and 67.0%, respectively. Patients with high serum HBsAg levels (> 250 IU/mL) had significantly lower survival rates than those with low HBsAg levels (HR: 1.517, 95% CI: 1.005-2.292, P = 0.047). Stratified analysis showed that patients with high HBsAg levels had a significantly higher late recurrence incidence than those with low HBsAg levels (HR: 2.155, 95% CI: 1.094-4.248, P = 0.026), but did not have a significantly higher risk of early recurrence postoperatively (HR: 1.320, 95% CI: 0.837-2.082, P = 0.233). Multivariate analysis revealed that HBsAg > 250 IU/mL was an independent risk factor associated with late recurrence (HR: 2.109, 95% CI: 1.068-4.165, P = 0.032). ConclusionsHBsAg > 250 IU/mL at the time of tumor resection was an independent risk factor for late recurrence in low viral load HCC patients.