Independent Predictor Of Early Recurrence Research Articles

High expression of ribonucleotide reductase subunit M2 correlates with poor prognosis of hepatocellular carcinoma.

Background/AimsRibonucleotide reductase subunit M2 (RRM2) catalyzes the production of deoxynucleotide triphosphates, which are necessary for DNA synthesis. RRM2 has been reported to play an active role in tumor progression, and elevated RRM2 levels have been correlated with poor prognosis for colorectal cancer patients. This study aimed to elucidate the prognostic significance of RRM2 protein expression in hepatocellular carcinoma after surgery.MethodsRRM2 protein expression was evaluated using immunohistochemistry in tumor tissues from 259 hepatocellular carcinoma patients who underwent curative hepatectomy.ResultsHigh RRM2 expression was observed in 210 of 259 patients (81.1%) with hepatocellular carcinomas. High RRM2 expression was significantly associated with viral etiology (p=0.035) and liver cirrhosis (p=0.036). High RRM2 expression was correlated with early recurrence (p=0.004) but not with late recurrence (p=0.144). Logistic regression analysis revealed that high RRM2 expression (p=0.040) and intrahepatic metastasis (p<0.001) were independent predictors of early recurrence. High RRM2 expression unfavorably influenced both shorter recurrence-free survival (p=0.011) and shorter disease-specific survival (p=0.002) and was an independent predictor of shorter disease-specific survival (p=0.008).ConclusionsHigh RRM2 protein expression might be a useful marker for predicting early recurrence and may be a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy.

New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment

New advances in precision medicine for hepatocellular carcinoma recurrence prediction and treatment

Prognosis of Recurrence after Complete Resection in Early-Stage Non-Small Cell Lung Cancer

BackgroundTumor recurrence is the most common cause of treatment failure, even after complete resection of early-stage non-small cell lung cancer (NSCLC). In this study, we investigated the prognosis of patients with early recurrence in order to identify independent risk factors related to early recurrence.MethodsBetween February 1995 and December 2012, 242 patients who underwent surgical resection for stage I NSCLC at Dong-A University Hospital were reviewed. The factors predicting overall survival (OS) and early recurrence were investigated. We also investigated the relationship between the patterns and period of recurrence and clinicopathological factors.ResultsFor patients with stage IA and IB NSCLC, the 5-year OS rate was 75.7% and 57.3% (p=0.006), respectively. A multivariate Cox proportional hazards model demonstrated that gender (p=0.004), comorbidity number (p=0.038), resection type (p=0.002), and tumor size (p=0.022) were the statistically significant predictors of OS. Moreover, the multivariate analysis revealed that smoking history (p=0.023) and histologic grade (p=0.012) were the independent predictors of early recurrence. Additionally, only histologic grade (poor differentiation) was found to be significantly associated with a higher frequency of distant metastasis; there was no relationship between the patterns and period of recurrence and clinicopathological factors.ConclusionThe present study demonstrated that smoking history and histologic grade were independent prognostic factors for early recurrence within two years in patients with early-stage NSCLC. Patients with these predictive factors may be good candidates for adjuvant therapy.

Early recurrence in patients undergoing curative surgery for colorectal cancer: is it a predictor for poor overall survival?

This study evaluated the prognostic value of early recurrence in patients who have undergone curative resection for colorectal cancer. A total of 1,159 consecutive patients who underwent curative resection for non-metastatic colorectal cancer from December 1998 to December 2007 were reviewed. The predictive factors for early recurrence postoperatively and the prognostic factors were analyzed. Of the 1,159 patients, postoperative recurrence was identified in 280 (24.1%) patients, and 96 (34.3%) of the 280 patients with recurrence were designed as early recurrence (less than 1 year postoperatively). In multivariate analysis, tumor location, tumor diameter, number of retrieved lymph nodes, and lymphovascular invasion were the independent predictors for early recurrence. The early recurrence group had a significantly lower overall survival rate than that of the non-early recurrence group for both colon cancer (P < 0.001) and rectal cancer (P < 0.001). The overall survival rate for stage III tumors significantly differed between the early and non-early recurred patients (P < 0.001), whereas the rate did not differ between the patients with stage II tumors (P = 0.364). In multivariate analysis, early recurrence was an independent predictor for unfavorable overall survival. Moreover, differentiation, N category, and postoperative chemotherapy were the independent predictors for overall survival for the patients with both early and overall recurrence. Poor survival was associated with early postoperative recurrence for patients who underwent curative resection for colorectal cancer. The use of adjuvant chemotherapy prolonged the survival of patients, irrespective of the interval of recurrence.

Expression of Fibroblast Growth Factor 19 Is Associated with Recurrence and Poor Prognosis of Hepatocellular Carcinoma

Fibroblast growth factor 19 (FGF19)-mediated activation of mitogen-activated protein kinase and the β-catenin pathway may be involved in the development and progression of hepatocellular carcinoma. This study aimed to elucidate the prognostic significance of FGF19 protein expression in hepatocellular carcinoma patients. By immunohistochemistry, we investigated the expression of FGF19 protein in tumor tissue from 281 hepatocellular carcinoma patients who underwent curative hepatectomy. Univariate and multivariate analyses were performed to evaluate its predictive value for tumor recurrence and survival of patients. The median follow-up period was 75.6 months. FGF19 protein expression was observed in 135 (48.0 %) of the 281 hepatocellular carcinomas. FGF19 expression was significantly associated with larger tumor size (P < 0.001), and higher BCLC stage (P = 0.001). FGF19 expression was correlated with the early recurrence (P < 0.001), but not with the late recurrence (P = 0.582). FGF19 expression (P = 0.002), viral etiology (P = 0.028), and intrahepatic metastasis (P < 0.001) were independent predictors of early recurrence. Multivariate analyses of survival revealed that FGF19 expression (P < 0.001), intrahepatic metastasis (P < 0.001), and liver cirrhosis (P = 0.019) were independent predictors of shorter disease-free survival. FGF19 expression (P = 0.005), larger tumor size (P = 0.038), major portal vein invasion (P = 0.048), intrahepatic metastasis (P < 0.001), lower albumin level (P = 0.024), and liver cirrhosis (P = 0.031) were independent predictors of shorter disease-specific survival. FGF19 protein expression might be an effective predictor of early recurrence and a marker for poor prognosis of hepatocellular carcinoma after curative hepatectomy, indicating that FGF19 might be a potential preventive target in hepatocellular carcinoma patients.

Breast cancer resistance protein expression is associated with early recurrence and decreased survival in resectable pancreatic cancer patients

The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismal even after complete resection, with most recurrences occurring within 1-2 years postoperatively. Adenosine triphosphate (ATP)-binding cassette (ABC) transporters have been demonstrated to play major roles in multidrug resistance (MDR) of cancers. In this study, we evaluated the expression statuses and the clinical significance of MDR1 (ABCB1), MDR-associated proteins (MRPs/ABCC) 1, 2 and 3, and breast cancer resistance protein (BCRP/ABCG2) in 67 surgically resected PDACs by immunohistochemistry. MDR1, MRP1, MRP2, MRP3 and BCRP were expressed in 35 (52.2%), 56 (83.6%), 61 (91.0%), 49 (73.1%) and 49 (73.1%) out of 67 cases, respectively. The expression statuses of the MDR-related proteins were positively correlated with each other (P < 0.05). Tumors expressing MRP1 (P= 0.015), MRP2 (P= 0.022) and MRP3 (P < 0.001) demonstrated more frequent perineural invasion. MDR1 expression was significantly correlated with lymphatic invasion (P= 0.047). High BCRP expression in PDAC was a significant prognostic factor for early tumor recurrence (HR = 2.43, P= 0.003) and poor survival (HR = 2.63, P= 0.001). MDR-related proteins are frequently expressed in PDAC, and high BCRP expression is a significant independent predictor for early recurrence and poor survival. Immunohistochemical analysis for BCRP expression in PDAC may be a useful test in identifying a subgroup of patients with a poor prognosis.

Right Atrial Anatomical Remodeling Affects Early Outcomes of Nonvalvular Atrial Fibrillation After Radiofrequency Ablation

The impact of the right atrial (RA) anatomical remodeling on outcomes of atrial fibrillation (AF) after radiofrequency ablation (RFA) is unclear. Sixty-three patients (50 men, 57±10 years, 23 persistent AF [PeAF]) who underwent RFA for AF were enrolled. Both RA and left atrial (LA) volumes, measured with multidetector computed tomography, as well as echocardiographic parameters were compared between subjects with early (<3 months, n=13) or 1-year (n=19) recurrence after RFA and without recurrence. The RA volume index (RAVI) was larger (98±21 vs. 77±22 ml/m²) and PeAF was more common (62% vs. 30%) in the early recurrence group (P<0.05 for all), whereas the LA volume index (LAVI) was similar between the 2 groups (78±15 vs. 72±19 ml/m², P=0.23). Notably, RAVI was the only independent predictor of early recurrence (for each 10 ml/m² increase, OR: 1.650, 95%CI: 1.017-2.677, P=0.04). PeAF was the only independent predictor of 1-year recurrence after RFA (OR: 4.496, 95%CI: 1.110-18.211, P=0.04), whereas RAVI and LAVI were not. RA anatomical remodeling might affect the early recurrence of AF after RFA. However, the chronicity of AF, rather than RA and LA anatomical remodeling, is a determinant of 1-year recurrence of AF after RFA.

Good quality white‐light transurethral resection of bladder tumours (GQ‐WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non‐muscle‐invasive bladder cancer: validation across time and place and recommendation for benchmarking

Study Type - Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Apart from bladder tumour multiplicity, size, stage, grade and presence of cis, early recurrence following white light TURBT for new bladder tumours is also determined by surgeon experience, completeness of resection and presence or absence of detrusor muscle in the specimen. This study aims to validate surgeon experience and detrusor muscle as independent predictors of early recurrence following apparently complete white light TURBT in new bladder tumours. To validate in patients undergoing first transurethral resection of bladder tumour (TURBT) for non-muscle-invasive bladder cancer (NMIBC), the presence/absence of detrusor muscle (DM) in the specimen and surgeon experience as independent predictors of the quality of TURBT. Patients with new NMIBC, who had undergone complete first resections were recruited from a prospectively maintained cohort from the 1980s at the Western General Hospital, Edinburgh, UK and a contemporary cohort from the Aberdeen Royal Infirmary, UK. Tumour size, multiplicity, surgeon category, presence or absence of DM in the specimen, grade, stage, findings at first check cystoscopy and early re-TURBT were evaluated. Surgeons were stratified into a senior group (consultant and trainees in year five or six) and a junior group (trainees below year five). Early recurrence, or recurrence rate at the first follow up cystoscopy (RRFFC), was used to measure quality and was defined as finding pathologically confirmed tumour at early re-TURBT or the first check cystoscopy. From a total of 566 patients evaluated from both cohorts, 473 NMIBC specimens were suitable for analysis. Logistic regression multivariate analysis revealed that the absence of DM was associated with a higher RRFFC (odds ratio [OR]= 3.6, 95% CI = 1.7-7.5, P < 0.001). Senior surgeons were more likely to resect DM (OR = 4.9, 95% CI = 2.3-10.7, P < 0.001) Senior surgeons were independently associated with a lower RRFFC (OR = 5.3, 95% CI = 2.1-12.9, P < 0.001). Detrusor muscle status at the first, apparently complete, TURBT and surgeon's experience independently predict the quality of TURBT. • Documented complete resection by experienced surgeons with DM presence (good quality white-light TURBT) should be considered a benchmark for white-light TURBT in NMIBC.

Predictors and outcome of early recurrence after resection of hepatic metastases from colorectal cancer

This study aimed to investigate the risk factors for early recurrence in patients who had undergone curative resection of colorectal liver metastases (CRLM) and to evaluate the outcome after recurrence. A total of 119 patients were divided into 2 groups: an early recurrence group (n = 54) who had recurrence within 2 years of curative resection of CRLM and a 2-year recurrence-free group (n = 65) who remained disease-free for at least 2 years following surgery. During the initial 5-year period after surgery, 4 out of 65 patients (6%) in the 2-year recurrence-free group and 29 out of 54 patients (54%) in the early recurrence group died. Multivariate analysis showed that postoperative morbidity was an independent predictor of early recurrence after curative resection of CRLM. Early recurrence is the leading cause of death within 5 years after curative resection of CRLM. Postoperative morbidity increases the risk of early recurrence in these patients. A reduction in perioperative morbidity may, therefore, improve the outcome of curative resection, as well as reducing medical costs.

Reduced NKG2D ligand expression in hepatocellular carcinoma correlates with early recurrence

The activating receptor natural killer group 2, member D (NKG2D) and its ligands play a crucial role in immune response to tumors. NKG2D ligand expression in tumors has been shown to be associated with tumor eradication and superior patient survival, but the involvement of NKG2D ligands in the immune response against hepatocellular carcinoma (HCC) still remains to be elucidated. We investigated the expression of NKG2D ligands in HCC tissues collected from 54 patients and HCC cell lines. We also examined the proteasome expression and the effect of inhibition of proteasome activity on NKG2D ligand expression in HCC tissues and cell lines. In dysplastic nodules (DN), well-differentiated (well-HCC), and moderately-differentiated HCCs (mod-HCC), UL16-binding protein (ULBP) 1 was expressed predominantly in tumor cells, but not in poorly-differentiated HCCs (poor-HCC). Remarkably, recurrence-free survival of patients with ULBP1-negative HCC was significantly shorter than that of patients with ULBP1-positive HCC (p=0.006). Cox regression analysis revealed that loss of ULBP1 expression was an independent predictor of early recurrence (p=0.008). We confirmed that ULBP1 was expressed in the well- and mod-HCC cell lines, but not in the poor-HCC cell line KYN-2. However, inhibition of proteasome activity resulted in significant up-regulation of ULBP1 expression in KYN-2. Moreover, we found that 20S proteasome expression was more abundant in KYN-2 than that in the well- and mod-HCC cell lines. ULBP1 is prevalently expressed in DN to mod-HCC, but loss of its expression correlates with tumor progression and early recurrence.

Importin-α1 as a Novel Prognostic Target for Hepatocellular Carcinoma

Perturbations in the nuclear microenvironment, including transport systems, play a critical role in malignant progression, but the nuclear import abnormalities remain unclear in hepatocarcinogenesis. We analyzed the role of importin in hepatocellular carcinoma (HCC). Gene expression profiling of the importin family was performed in HCC tissues. The significance of importin protein expression was analyzed in vitro as well as clinicopathologically. According to the microarray profiles, the importin-α1 was dominantly overexpressed in HCC tissues as compared to the adjacent noncancerous tissues. By means of human HCC cell lines, a knockdown of importin-α1 by its siRNA greatly reduced cellular proliferation by 15.2-26.6% (P < 0.005). Immunohistochemical analysis on tissue samples demonstrated cancer-specific overexpression in 36.3% of HCCs. The overexpression of importin-α1 was correlated statistically with high levels of alfa-fetoprotein ( P = 0.0017), the tumor number (P = 0.0116), histological dedifferentiation (P = 0.0054), tumor morphology (P = 0.0433), portal vein invasion (P = 0.0007), hepatic vein invasion (P = 0.0081), Fc (P = 0.0367), Fc-inf (P = 0.0122), and the tumor, node, metastasis stage (P = 0.0026); this resulted in a significantly poorer prognosis in both overall survival (P = 0.0164) and recurrence-free survival (P = 0.0101). Multivariate analysis of recurrence-free survival revealed importin-α1 expression to be a statistically significant factor (P = 0.0361). In addition, early recurrence after curative resection was observed more frequently in the importin-α1-positive group as compared to the negative group (P = 0.0023). The multivariate analysis identified importin-α1 as the only independent predictor of early recurrence after HCC resection (odds ratio = 5.291, P = 0.0191). Because importin-α1 might be closely associated with HCC progression, further analysis should be pursued to evaluate it as a novel prognostic target.

The eNOS Gene Single Nucleotide Polymorphism Is Associated with Early Recurrence of Atrial Fibrillation after Radiofrequency Catheter Ablation

Background: Previous reports have demonstrated the association between eNOS gene single nucleotide polymorphism (SNP) and atrial fibrillation (AF). This study evaluated whether eNOS gene variants are associated with AF recurrence after radiofrequency catheter ablation. Methods: A total of 295 consecutive patients (mean age 56±11 years, 78% male) with drug-refractory paroxysmal (68.7%) or persistent (31.3%) AF who underwent catheter ablation were included. Two SNPs, rs2070744 and rs1799983 were genotyped. Results: Early recurrence (ER) of AF (within 3 months) was observed in 33.7%, whereas late recurrence (LR) of AF (after 3 months) occurred in 23.1% of the patients during the median 12 months follow-up. The patients with persistent AF had more ER (40.8% vs. 26.4%, p=0.012). Genotype frequencies of the rs2070744 variant in patients with ER or LR were similar to those without ER or LR. In contrast, carriers of the variant allele (T) of the rs1799983 had an increased risk of ER (OR 2.357, 95% CI 1.194–4.652, p=0.013). Multiple logistic regression analysis showed that the rs1799983 variant (OR 2.512, 95% CI 1.245–5.068, p=0.010) and persistent AF (OR 1.938, 95% CI 1.088–3.451, p=0.025) were independent predictors of ER. Conclusions: The variant of rs1799983 in eNOS gene may increase the risk for early recurrence of AF after catheter ablation via decreased eNOS gene activity.

Predictors of Timing and Patterns of Recurrence after Curative Resection for Gastric Cancer

Aims: The aim of the study was to characterize recurrence patterns and identify predictors of recurrence after curative resection. Methods: Of 2,786 patients that underwent curative resection for gastric cancer from 2001 to 2006 at the Korean National Cancer Center, 439 (15.8%) experienced recurrence. Patterns of recurrence, clinicopathological characteristics, and therapeutic modalities were compared between 251 patients who had recurrence within 1 year (the early recurrence group) and 188 patients who had recurrence after more than a year (the late recurrence group). Multivariate analysis was performed to identify independent factors associated with the timing of recurrence. Results: In the early recurrence group, the most common pattern was hematogenous metastasis, and in the late recurrence group, the most common pattern was locoregional and peritoneal recurrence. The early recurrence group was characterized by a larger tumor, frequent lymph node (LN) metastasis, and venous, and perineural invasion. Multivariate analysis showed that LN metastasis and venous invasion were independent predictors of early recurrence. Median survival after recurrence was significantly shorter in the early recurrence group (p < 0.001). Conclusion: Hematogeneous metastasis was more common in the early recurrence group and LN metastasis and venous invasion were independent predictors of the timing of recurrence.

Phase 1/2 study of preoperative docetaxel and mitoxantrone for high‐risk prostate cancer

: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence. : Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m(2) and escalating mitoxantrone to 4 mg/m(2) before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence-free survival. Disease recurrence was defined as a confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. : Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%-78.0%) and was 49.8% at 5 years (95% CI, 35.5%-64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence. : Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high-risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified. Cancer 2010. (c) 2010 American Cancer Society.

High Plasma Levels of Factor VIII and Factor IX Increased the Incidence of Recurrent VTE.

Abstract 5070The aim of this study was to evaluate the diagnostic accurancy of the measurement of procoagulant factors FVIII and FIX levels and the risk of recurrence of venous thromboembolism (VTE). We have studied 56 patients (14 male, 42 female) with an objectively diagnosis of first deep vein thrombosis enrolled from February 2003 to February 2008, all patients were <60 years, without known malignancies, heart failure, chronic lung disease, infection, recent surgery, or genetic defects as Factor V Leiden (FV-Arg 506 Glu), prothrombin G20210A, deficiencies of Protein S or C or ATIII, hyperhomocysteinemia, dysfibrinogenemias; with increased levels of FVIII (>218 IU/dl), and FIX (>136 UI/dl). FVIII and FIX antigen levels were measured by ELISA. All patients received subcutaneous low molecular-weight eparin as thromboprophylactic treatment for the first 3 month after primary VTE, color Doppler ultrasonography (DUS) was performed periodically after primary VTE, the venous hemodynamic parameters studied included: blood flow velocity (cm/sec), vein cross sectional area (cm/2) blood volume flow (ml/sec), and microvascular injury was evaluated. Our studies have confirmed that a markedly elevated plasma levels of FVIII >256 IU/dl (range 218-294), and FIX >164IU/dl (range 136-192) among the patients with first episode of VTE are independent predictors of early recurrence about 52-74%: these patients have increased fibrin formation, D-Dimer levels (234.6ng/ml), and blood rheologic variables such as plasma viscosity are still present in all patients: plasma viscosity mPa/s shear rate >1.98 and blood viscosity mPa/s shear rate >3.48 especially under low shear conditions. These factors show to be associated with VTE and above all with the recurrence (54 patients), and emerged as relatively independent of other thrombophilic factors. The higt risk of VTE recurrence in these patients requires strategies for its prevention: secondary prophylaxis with the administration of standard oral anticoagulant at moment the use of coumarins (INR: 2.0-3.0) and possibly the need for prolonged, probably life-long treatment. DisclosuresNo relevant conflicts of interest to declare.

Usefulness of C-reactive protein in predicting early and late recurrences after atrial fibrillation ablation

We studied the C-reactive protein level and its predictive value for early and late arrhythmia recurrences after atrial fibrillation (AF) ablation. We analysed data from 125 consecutive patients (52% with paroxysmal AF) who underwent a first AF ablation. C-reactive protein level was determined at baseline and at Days 1, 2, and 3 post-AF ablation. An early recurrence (ER) was defined as any arrhythmia occurring within the first month following the index ablation. Sixty-eight patients (54%) experienced ER. Twenty-nine patients were re-ablated for ER within the first month and were not included for the long-term follow-up analysis. Of the remaining 96 patients, 59 (61%) experienced late recurrences. C-reactive protein level increased significantly after AF ablation with a peak (40 +/- 32 mg/L) occurring 2 days after the index procedure. Patients without ER had a significant higher C-reactive protein level (49 +/- 52 vs. 32 +/- 22 mg/L, P=0.02) compared with patients without ER. However, the C-reactive protein level was similar in patients with or without late recurrences. C-reactive protein level was the only independent predictor of ERs (P = 0.03). C-reactive protein level increased significantly after AF ablation. High C-reactive protein level was associated with fewer early arrhythmia recurrences. No relationship was found between C-reactive protein level and late arrhythmia recurrences.

Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER+) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER+ EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum). The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

Risk factors for early recurrence after surgical resection for hepatocellular carcinoma

Early recurrence (ER) after liver resection is one of the most important factors impacting the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aimed to identify the factors associated with ER after curative hepatic resection for HCC. From the July 2000 to July 2006, 144 patients underwent hepatic resection for HCC at a single institution. After excluding those with ruptured HCC, combined or mixed HCC, and who died during admission, 116 patients were analyzed. Patients with ER (defined as within 1 year) were compared with those who remained free of disease for more than 1 year. Various clinical characteristics including tumor and operative factors were evaluated to determine the factors predicting postoperative ER using univariate and multivariate analyses. ER occurred in 51 patients (44%). In the univariate analysis, tumor size (P=0.001), microvascular invasion (P=0.003), portal vein invasion (P=0.001), TNM stage (P=0.010), serum levels of alpha-fetoprotein (AFP) (P=0.002) and aspartate aminotransferase (AST) (P=0.011), and operative time (P=0.033) were significantly associated with ER. AFP and AST were the independent predictors of ER in the multivariate analysis (P<0.05). Preoperative serum AFP and AST levels were the independent risk factors for ER after surgical resection for HCC. Close postoperative surveillance is recommended for early detection of recurrence and additional treatments in patients with these factors.

Expression of dystroglycan correlates with tumor grade and predicts survival in renal cell carcinoma

The dystroglycan (DG) complex is a transmembrane glycoprotein that forms a continuous link from the extracellular matrix to the actin cytoskeleton. Deregulated expression of DG has been reported in a variety of human malignancies and related to tumor aggressiveness. In this study expression of the α-DG subunit was evaluated by immunostaining in a series of renal epithelial cancers and its relation with traditional prognostic indicators and with the clinical outcome of the patients was evaluated. α-DG expression was undetectable in a significant fraction of tumors (54%). In renal cell carcinomas (RCC) loss of DG staining correlated with higher tumor grade (p = 0.02) but not with tumor stage nor tumor size. In clear cell RCC patients loss of α-DG staining correlated with an increased risk of recurrence (p = 0.002 by log-rank test) and death (p = 0.004) also when patients with lower grade or stage tumors were analyzed separately. In a multivariate analysis loss of DG staining confirmed to be and independent predictor of shorter disease-free (p = 0.001; RR = 4.9) and overall (p = 0.009; RR = 4.9) survival stronger than tumor grade and size. These findings demonstrate that loss of α-DG expression, which correspond to loss of a functional DG complex, is a frequent event in human renal tumorigenesis and is an independent predictor of early recurrence and death for patients with clear cell RCC.

The Role of Paraaortic Lymph Node Involvement on Early Recurrence and Survival after Macroscopic Curative Resection with Extended Lymphadenectomy for Pancreatic Carcinoma

Early recurrence of invasive pancreatic cancer is common even after curative resection. To establish appropriate selection criteria for radical surgery, it is essential to identify the patient population at risk for early recurrence. One hundred thirty-three of 136 patients who underwent potentially curative pancreatectomy for invasive ductal adenocarcinoma of the pancreas between 1999 and 2003 were divided into two groups: patients whose recurrence developed within 1 year after operation and those whose recurrence did not develop within 1 year. Clinicopathologic factors were retrospectively analyzed between these groups using univariate and multivariable methods. One postoperative death occurred, yielding an in-hospital mortality rate of 0.7% (of 136 patients). Eighty-one patients (61% of 133) were identified as having recurrent pancreatic carcinoma within a year. Paraaortic nodal involvement and positive washing cytology were independent predictors of early recurrence. The median survival time in 26 patients with paraaortic nodal involvement was 13 months, versus 30 months in 106 patients without paraaortic nodal involvement (p < 0.001). Paraaortic lymph node involvement was notably associated with elevated CA19-9 a month after operation (p = 0.03), larger tumor size (p = 0.02), and a positive surgical margin (p = 0.04). Sampling of paraaortic lymph nodes is recommended as a routine examination at laparotomy. When positive nodes are confirmed by frozen section, early recurrence and poor survival are inevitable, even after radical operation including extended lymphadenectomy.