Risk Factors For Poor Disease-free Survival Research Articles

Sarcopenia Predicts Postoperative Complications and Survival of Colorectal Cancer Patients Undergoing Radical Surgery.

Aims/Background Previous literature has indicated that sarcopenia is related to poor outcomes after radical resection for colorectal cancer (CRC). However, its effect on the postoperative clinical outcomes of CRC remains controversial. This study aimed to elucidate the predictive value of sarcopenia for postoperative complications and survival in CRC patients. Methods This investigation retrospectively assessed the clinical data of 226 CRC patients who underwent radical resection at the Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University from January 2018 to December 2020. Sarcopenia was diagnosed according to the recommendations of the Asian Working Group for Sarcopenia in 2019, and patients were categorized into sarcopenia and non-sarcopenia groups. Multivariate and univariate analyses were employed to assess the risk factors for postoperative complications. The Kaplan-Meier method and survival curve were used to analyze postoperative survival time. Cox proportional hazards regression models were used to evaluate risk factors affecting the prognosis of CRC patients. Results This investigation included 226 patients, of which 68 were diagnosed with sarcopenia. Furthermore, it was revealed that sarcopenia was linked with older age (p < 0.001), low body mass index (p < 0.001), high prevalence of diabetes (p = 0.002), high cystatin level (p = 0.017), and low 3rd lumbar spine (L3) planar skeletal muscle index (p < 0.001), but was not related to the tumour stage or the gender. Moreover, sarcopenia was also correlated with increased occurrence of all postoperative complications (p = 0.050). The results of the multivariate analysis indicated that sarcopenia was an independent risk factor for postoperative complications (odds ratio (OR): 7.154; 95% confidence interval (CI): 2.261-22.633; p = 0.017). The Kaplan-Meier analysis revealed that sarcopenia patients had significantly lower 5-year disease-free survival (DFS) (48.5% vs 59.5%; log-rank p = 0.033) and 5-year overall survival (OS) (57.4% vs 77.2%; log-rank p < 0.001) rates. Sarcopenia was an independent risk factor for poor DFS (hazard ratio (HR) = 1.404; p = 0.016) and OS (HR = 1.290; p = 0.021). Conclusion In CRC patients undergoing radical surgery, sarcopenia is an independent risk factor for postoperative complications. Sarcopenia may be a predictive factor for the prognosis and survival of CRC patients undergoing radical resection.

Beneficial implications of adjuvant chemotherapy for stage IB lung adenocarcinoma exhibiting elevated SUVmax in FDG-PET/CT: a retrospective study from a single center.

Controversy surrounds the efficacy of adjuvant chemotherapy (ACT) in the treatment of stage I lung adenocarcinoma (LUAD). The objective of this study was to examine the impact of the maximum standardized uptake value (SUVmax) as measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) on the efficacy of ACT in patients diagnosed with stage I LUAD. We scrutinized the medical records of 928 consecutive patients who underwent complete surgical resection for pathological stage I LUAD at our institution. The ideal cut-off value for primary tumor SUVmax in terms of disease-free survival (DFS) and overall survival (OS) was determined using the X-tile software. The Kaplan-Meier method and Cox regression analysis were used for survival analysis. Based on the SUVmax algorithm, the ideal cutoff values were determined to be 4.9 for DFS and 5.0 for OS. We selected 5.0 as the threshold because OS is the more widely accepted predictive endpoint. In a multivariate Cox regression analysis, SUVmax ≥ 5.0, problematic IB stage, and sublobectomy were identified as independent risk factors for poor DFS and OS. It is noteworthy that patients who were administered ACT had significantly longer DFS and OS than what was observed in the subgroup of patients with pathological stage IB LUAD and SUVmax ≥ 5.0 (p < 0.035 and p ≤ 0.046, respectively). However, there was no observed survival advantage for patients in stages IA or IB who had an SUVmax < 5.0. The preoperative SUVmax of tumors served as an indicator of the impact of ACT in the context of completely resected pathological stage I LUAD. Notably, patients within the Stage IB category exhibiting elevated SUVmax levels emerged as a subgroup experiencing substantial benefits from postoperative ACT.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

Tumor burden score dictates prognosis of patients with combined hepatocellular cholangiocarcinoma undergoing hepatectomy.

The prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery. Patients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan-Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS. A total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan-Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort. The present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.

Impact of disintegrin and metalloproteinase domain-containing protein 12 on pancreatic ductal adenocarcinoma treated with surgical resection and perioperative chemotherapy

Background/Objectives:A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) has been reported to influence tumor progression and chemosensitivity in human cancers. We assessed the prognostic impact of ADAM12 and its predictive value for neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection. MethodsADAM12 expression was immunohistochemically examined in 428 patients with PDAC who underwent surgical resection. The association of ADAM12 expression with clinicopathological factors and survival was also analyzed. ResultsPatients with high ADAM12 expression exhibited significantly shorter median disease-free survival (DFS) (high ADAM12: 17.8 vs. low ADAM12: 37.9 months; P < 0.001) and overall survival (OS) (high ADAM12: 33.1 vs. low ADAM12: 65.0 months; P < 0.001). A multivariate analysis revealed that high ADAM12 expression was an independent risk factor for poor DFS (P < 0.001) and OS (P < 0.001) in all eligible patients. Of 100 patients who received neoadjuvant chemotherapy (NAC), high ADAM12 expression was significantly associated with poor DFS in a subset of patients treated with the nab-paclitaxel (PTX) neoadjuvant regimen (P = 0.03), whereas the prognostic value of ADAM12 was not evident in patients not treated with nab-PTX (P = 0.12). ConclusionsA negative prognostic value of high ADAM12 expression was observed in patients with PDAC treated with surgical resection, which was enhanced in patients treated with NAC, including nab-PTX. These results suggested that ADAM12 expression can predict nab-PTX chemosensitivity in PDAC and reflect PDAC progression.

ASF1B: A Possible Prognostic Marker, Therapeutic Target, and Predictor of Immunotherapy in Male Thyroid Carcinoma.

BackgroundThyroid carcinoma (TC) is the most common malignant endocrine tumor worldwide. Several studies have documented that male patients with TC have a higher rate of metastasis and disease recurrence than female patients. However, the mechanism underlying this observation is not completely clear. The goal of our research was to investigate the potential key candidate genes and pathways related to TC progression in male patients at the molecular level.MethodsA total of 320 samples were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Hub genes were screened out using weighted gene coexpression network analysis (WGCNA) and a protein–protein interaction (PPI) network analysis. Survival analysis was used to identify hub genes associated with disease-free survival (DFS) rates. Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression (ESTIMATE) data were used to assess the relationship between hub genes and immune cell infiltration. The molecular mechanism and biological functions of hub genes were explored using RT-qPCR, Western blot, Cell Counting Kit-8 Assay, flow cytometry, Transwell assays, and scratch assays.ResultsForty-seven hub genes were identified, and the survival analysis demonstrated that anti-silencing function 1B (ASF1B) was the sole independent risk factor for poor DFS in male TC patients. Possible associations between the results from the ESTIMATE analysis showed that the ASF1B expression level was related to the ESTIMATE score, immune score, and T-cell regulatory (Treg) infiltration level. Through in vitro cell function experiments, we verified that knockdown of ASF1B inhibited KTC-1 cell proliferation, promoted cell apoptosis, and blocked cell cycle. The silencing of ASF1B reduced protein kinase B (AKT), phospho-AKT (p-AKT), and forkhead box p3 (FOXP3) in KTC-1 cells. Moreover, FOXP3 overexpression markedly restored the cell migration, invasion, and proliferation abilities repressed by ASF1B knockdown.ConclusionsOur results indicate that ASF1B can be considered a prognostic marker, therapeutic target, and predictor of immunotherapy response in male thyroid cancer patients. However, further in-depth studies are required to validate this finding.

Discovering novel mechanisms of taxane resistance in human breast cancer by whole-exome sequencing.

Taxanes are important drugs used in the treatment of breast cancer; however, some cancer types are taxane-resistant. The aim of the present study was to investigate the underlying mechanisms of taxane resistance using whole-exome sequencing (WES). Six patients with breast cancer whose tumors responded well to anthracycline treatment but grew rapidly during neoadjuvant taxane-based chemotherapy, were included in the present study. WES of samples from these patients was carried out to identify somatic mutations of candidate genes thought to affect taxane resistance, and the candidate proteins were structurally modeled. The mRNA and protein expression levels of these candidate genes in other breast cancers treated with taxanes were also examined. Nine variants common to all six patients were identified and two of these [R552P in V-type proton ATPase catalytic subunit A (ATP6V1A) and T114P in apolipoprotein B MRNA editing enzyme catalytic subunit 3F (APOBEC3F)] were selected. The results also showed that, protein-structure visualization suggested that these mutations may cause structural changes. The Kaplan-Meier analyses revealed that higher APT6V1A and APOBEC3F expression levels were significantly associated with poorer disease-free survival (DFS) and overall survival. Moreover, multivariate analysis identified high ATP6V1A mRNA expression as an independent risk factor for poor DFS. Two specific mutations that might affect taxane resistance were identified. Thus, these results suggest that breast cancer patients receiving taxanes who have high ATP6V1A or APOBEC3F expression levels may have shorter survival.

Prognostic Value of Third Cervical Vertebra Skeletal Muscle Index in Oral Cavity Cancer: A Retrospective Study.

To assess the prognostic utility of third cervical vertebra skeletal muscle index (C3 SMI) measured from preoperative head and neck computed tomography (CT) in patients with oral cavity squamous cell carcinoma (OSCC). Retrospective study. We retrospectively reviewed the medical records of 125 patients who underwent primary curative surgery for OSCC between 2009 and 2017. Their preoperative C3 SMI was calculated by adjusting the C3 cross-sectional area delineated on head and neck CT by body height squared. A Cox proportional hazard model was employed to identify prognostic factors, and a novel nomogram based on C3 SMI was built for individualized survival prediction. In Kaplan-Meier analysis, high C3 SMI was significantly associated with higher 5-year disease-free survival (DFS) and overall survival (OS) than low C3 SMI. In multivariate analysis, low C3 SMI was an independent risk factor for poor DFS and OS (hazard ratio [HR]: 2.197; 95% confidence interval [CI], 1.170-4.512, P= .032 and HR: 2.143; 95% CI, 1.232-3.728, P= .007, respectively). The concordance-index (C-index) of the nomogram based on C3 SMI was 0.814 for OS, higher than that of the nomogram based on tumor-node-metastasis staging alone (C-index=0.731). C3 SMI might serve as a novel prognosticator in OSCC patients undergoing curative surgery, and the nomogram based on C3 SMI might provide good prognostic discrimination ability for individualized survival prediction. IV Laryngoscope, 131:E2257-E2265, 2021.

Volume Doubling Times of Lung Adenocarcinomas: Correlation with Predominant Histologic Subtypes and Prognosis.

Background The volume doubling time (VDT) is a key parameter in the differentiation of aggressive tumors from slow-growing tumors. How different histologic subtypes of primary lung adenocarcinomas vary in their VDT and the prognostic value of this measurement is unknown. Purpose To investigate differences in VDT between the predominant histologic subtypes of primary lung adenocarcinomas and to assess the correlation between VDT and prognosis. Materials and Methods This retrospective study included patients who underwent at least two serial CT examinations before undergoing operation between July 2010 and December 2018. Three-dimensional tumor segmentation was performed on two CT images and VDTs were calculated. VDTs were compared between predominant histologic subtypes and lesion types by using Kruskal-Wallis tests. Disease-free survival (DFS) was obtained in patients undergoing surgical procedures before July 2017. Univariable and multivariable Cox proportional hazards regression analyses were performed to determine predictors of DFS. Results Among 268 patients (mean age, 64 years ± 8 [standard deviation]; 143 men), there were 30 lepidic, 87 acinar, 109 papillary, and 42 solid or micropapillary predominant subtypes. The median VDT was 529 days (interquartile range, 278-872 days) for lung adenocarcinomas. VDTs differed across subtypes (P < .001) and were shortest in solid or micropapillary subtypes (229 days; interquartile range, 77-530 days). Solid lesions (VDT, 248 days) had shorter VDTs than subsolid lesions (part-solid lesions, 665 days; nonsolid lesions, 648 days) (P < .001). In the 148 patients (mean age, 64 years ± 8; 89 men) included in the survival analysis, 35 patients had disease recurrence and 17 patients died. VDT (<400 days) was an independent risk factor for poor DFS (hazard ratio, 2.6; P = .01) and higher TNM stage. Adding VDT to TNM stage improved model performance (C-index, 0.69 for TNM stage vs 0.77 for combined VDT class and TNM stage; P = .002). Conclusion Volume doubling times varied significantly according to the predominant histologic subtypes of lung adenocarcinoma and had additional prognostic value for disease-free survival. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Ko in this issue.

High Preoperative Controlling Nutritional Status Score Predicts a Poor Prognosis in Patients with Localized Upper Tract Urothelial Cancer: A Propensity Score Matching Study in a Large Chinese Center.

PurposeThe aim of this study was to elucidate the prognostic value of the preoperative controlling nutritional status (CONUT) score, a new index based on the total lymphocyte count, serum albumin concentration and total cholesterol concentration, in patients with localized upper tract urothelial cancer (UTUC) after radical nephroureterectomy (RNU) using propensity score matching (PSM) analysis.MethodsWe retrospectively reviewed 908 consecutive patients with localized UTUC who underwent RNU between 1999 and 2015. Patients were divided into two groups according to the optimal cutoff value of the preoperative CONUT score. Relationships between the CONUT score with clinicopathological characteristics, overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) were analyzed before and after 1:1 PSM.ResultsA high preoperative CONUT score was significantly correlated with older age, low body mass index (BMI), poor American Statistical Association (ASA) score, advanced pathological T stage, and tumor squamous or glandular differentiation (all p<0.05). Kaplan-Meier curves showed poor OS, CSS, and DFS for patients with a high CONUT score before and after PSM (all p<0.001). Furthermore, multivariate analyses revealed that a high preoperative CONUT score was an independent risk factor for poor DFS (hazard ratio [HR] 1.418, 95% confidence interval [CI] 1.132–1.776, p=0.002) before PSM and an independent risk factor for poor DFS (HR 1.333, 95% CI 1.010–1.760, p=0.042) and OS (HR 1.459, 95% CI 1.010–2.107, p=0.044) after PSM.ConclusionA high preoperative CONUT score is an independent prognostic factor for poor outcomes in patients with localized UTUC after RNU.

Analysis of Tumor Genomic Pathway Alterations Using Broad-Panel Next-Generation Sequencing in Surgically Resected Lung Adenocarcinoma.

The majority of broad-panel tumor genomic profiling has used a gene-centric approach, although much of that data is unused in clinical decision making. We hypothesized that a pathway-centric approach using next-generation sequencing (NGS), combined with conventional clinicopathologic features, may better predict disease-free survival (DFS) in early stage lung adenocarcinoma. Utilizing our prospectively maintained database, we analyzed 492 patients with primary, untreated, completely surgically resected lung adenocarcinoma. Ten canonical pathways were analyzed using broad-panel NGS. The correlations of DFS and number (and type) of pathway (NPA) were analyzed using the Kaplan-Meier method and log-rank test. Associations between altered pathways and clinicopathologic variables, as well as identification of actionable therapeutic strategies were explored. Median NPA for the cohort was two (range, 0-5). Smoking status, solid morphologic appearance on preoperative CT, maximal standardized uptake value, pathologic tumor size, aggressive histologic subtype, lymphovascular invasion, visceral pleural invasion, and positive lymph nodes were significantly associated with NPA (P < 0.05). Of 543 actionable genetic alterations identified, 455 (84%) were within the RTK/RAS pathway. A total of 86 tumors had actionable therapeutic genomic alterations in >1 pathway. On multivariable analysis, higher NPA was significantly associated with worse DFS (HR, 1.31; P = 0.014). NPA and specific pathway alterations are associated with clinicopathologic features in patients with surgically resected lung adenocarcinoma. Cell cycle, Hippo, TGFβ, and p53 pathway alterations are associated with poor DFS. Finally, NPA is an independent risk factor for poor DFS in our cohort.See related commentary by Blakely, p. 7269.

548P - Local immune status in cancer cell nests can be a predictor of survival for rectal cancer with neoadjuvant radiotherapy

BackgroundAlthough neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer (LARC), it remains difficult to predict the prognosis of LARC patients. We aimed to explore the impacts of local immune status on survival of LARC after noeadjuvant radiotherapy (nRT). MethodsA total of 76 consecutive LARC patients were enrolled in our institute from February 2012 to September 2015. CD3+ T-cell and CD8+ T-cell count were determined from surgical specimens. Factors associated with disease-free survival (DFS) and overall survival (OS) were identified by univariate and multivariate Cox regression. SPSS 22.0 was used for statistical analyse. ResultsThe median follow-up time was 29.0 months (range 2.0-59). The Cutoff Finder software identified an optimal CD3+ T-cell cutoff value of 12.5% and CD8+ T-cell value of 9% for our patients. According to the Kaplan-Meier analysis, CD3+ T-cell ≥12.5% was significantly related to favorable DFS (P=0.020), while there was no significant difference between CD3+ T-cell and OS (P=0.238). Meanwhile, CD8+ T-cell ≥9% was found to have a positive effect on DFS and OS (P=0.012 and P=0.035, respectively). In the multivariate Cox regression model, CD8+ T-cell <9% was independent risk factors for poor DFS (HR=0.492, 95%CI= 0.252-0.960, P=0.038). Furthermore, CD8+ T-cell (HR=0.268, 95%CI= 0.076-0.941, P=0.040) and T stage (HR=0.151, 95%CI= 0.030-0.7530, P=0.021) were independent predictors of OS. ConclusionsHigh CD8+ T-cell count were significantly related to good survival in LARC patients with nRT. Local immune status was suggested to be measured in order to predict the prognosis of patients with LACR after nRT. Legal entity responsible for the studyXijin Lin. FundingThe Fujian Province Natural Science Foundation (2017J01260), Joint Funds for the Innovation of Science and Technology, Fujian province (2017Y9074), and the Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (2017 Open Project-9). DisclosureAll authors have declared no conflicts of interest.

Serum Alkaline Phosphatase Predicts Poor Disease-Free Survival in Patients Receiving Radical Gastrectomy.

BackgroundSerum alkaline phosphatase (ALP) has been proved to be a negative prognostic factor for several malignancies, but its clinical significance in gastric cancer (GC) patients has not been sufficiently studied. In the present retrospective study, we investigated the effect of serum ALP on disease-free survival (DFS) after radical gastrectomy.Material/MethodsWe included 491 GC patients receiving radical gastrectomy at the Chinese People’s Liberation Army 309th Hospital. Univariate and multivariate analyses were performed to determine factors influencing serum ALP and DFS. The changes in serum ALP and its clinical relevance were also analyzed using the log-rank test and Cox proportional hazards model.ResultsThere were 491 patients who met our inclusion and exclusion criteria. Pre-treatment serum ALP was elevated in 87 of these patients and was normal in the other 404 patients. Elevation of pre-treatment serum ALP was correlated with the tumor diameter (OR=2.642, P=0.017), TNM stage (OR=4.592, P=0.005), and T classification (OR=1.746, P=0.043). DFS was significantly different between patients with normal or elevated pre-treatment serum ALP (median 42.1 vs. 32.8 months, P=0.001) and multivariate analysis suggested pre-treatment serum ALP is an independent risk factor for poor DFS after radical gastrectomy (HR=2.035, P=0.021). In addition, removal of the primary tumor lesion led to an obvious decline in serum ALP activity (median 262 U/L vs. 152 U/L, P<0.001), and monitoring changes in serum ALP can help evaluate the risk of tumor relapse in GC patients (χ2=17.814, P<0.001).ConclusionsSerum ALP is a good predictor of GC patient DFS after radical gastrectomy, and patients with elevated serum ALP have shorter relapse times.

Postoperative adjuvant transarterial chemoembolization for multinodular hepatocellular carcinoma within the Barcelona Clinic Liver Cancer early stage and microvascular invasion.

The survival benefit of postoperative adjuvant transcatheter arterial chemoembolization (PA-TACE) remained controversial. We aimed to investigate the prognosis effect of PA-TACE on the Barcelona Clinic Liver Cancer (BCLC) early stage multinodular hepatocellular carcinoma (MHCC) patients with/without microvascular invasion (MVI). Two hundred and seventy-one patients from January 2010 to December 2014 undergoing curative hepatectomy were included in this study. Disease-free survival (DFS) rates and overall survival (OS) rates as well as prognostic factors were analyzed by the Kaplan-Meier method, the log-rank test and the Cox proportional hazard model. Thirty-four point four percent (44/128) MVI positive and 55.2% (79/143) MVI negative patients underwent PA-TACE. Multivariate analysis revealed that HBV DNA load >103 copy/mL, >three tumors, MVI, and without PA-TACE were independent risk factors for poor DFS. Higher alkaline phosphatase (ALP), three tumors, MVI, and without PA-TACE were independent risk factors for poor OS. Both DFS and OS were significantly improved in patients with MVI who received PA-TACE as compared to those who underwent hepatic resection alone (5-year DFS, 26.3% vs. 20.7%, P=0.038; 5-year OS, 73.6% vs. 47.7%, P=0.005). No differences were noted in DFS and OS among MVI negative patients with or without PA-TACE (5-year DFS, 33.7% vs. 33.0%, P=0.471; 5-year OS, 84.1% vs. 80.3%, P=0.523). Early recurrence was more likely to occur in patients without PA-TACE (P=0.001). PA-TACE was a safe intervention and could effectively prevent tumor recurrence and improve the survival of the BCLC early stage MHCC patients with MVI.

Serum Marker Score Based on Prognostic Nutrition Index, Carcinoembryonic Antigen, and Carbohydrate Antigen 19-9 Is Associated With Recurrence for Patients Undergoing Surgery for Pancreatic Ductal Adenocarcinoma.

The prognostic value of the prognostic nutrition index (PNI) in pancreatic ductal adenocarcinoma (PDAC) is still controversial. This study aimed to assess the correlation between PNI and the outcome for PDAC patients and to generate a new score from PNI and serum markers. This study investigated 151 patients who underwent pancreatic resection for PDAC between April 2002 and June 2012. Disease-free survival (DFS), overall survival, and clinicopathological parameters were analyzed according to the PNI value. The low PNI patients had poorer 5-year DFS rate than high-PNI patients (10.7% and 34.8%, respectively). Multivariate analyses revealed that independent risk factors for poor DFS were high carcinoembryonic antigen (hazard ratio [HR], 1.53; P = 0.038), high carbohydrate antigen 19-9 (HR, 1.67; P = 0.017), positive lymph node metastasis (HR, 1.98; P = 0.017), R1 or 2 resection (HR, 3.50; P < 0.001), and low PNI (HR, 0.37 [high/low]; P = 0.029]. Scoring based on the formula -0.49 × (PNI) + 0.41 × (carcinoembryonic antigen) + 0.67 × (carbohydrate antigen 19-9) was significantly associated with poor DFS (P < 0.001) and overall survival (P = 0.0019). Low PNI and serum marker score are significantly associated with poor DFS.

Lack of progesterone receptor expression predicts poor prognosis in patients with operable ER-positive invasive breast cancer

To investigate the impact of lack of progesterone receptor (PR) expression on the prognosis of patients with operable ER (estrogen receptor)-positive invasive breast cancer. We retrospectively analyzed the clinicopathological features, treatment and survival data of 318 women with ER+ /PR+ and ER+ /PR- invasive breast cancer. Among the 318 patients, there were 219 PR-positive and 99 PR-negative cases. The 5-year overall survival (OS) rate was 92.5%, and the 5-year disease-free survival (DFS) rate was 87.2% in the 318 ER-positive patients. Among them, the 5-year OS rates were significantly different between the PR-positive group (94.6%) and PR-negative group (87.8%, P=0.020), and the 5-year DFS rates were also significantly different from each other (89.8% and 81.6%, respectively, P=0.019). Univariate analysis showed that PR status, tumor size, T stage, axillary lymph node metastasis, and clinical stage were prognostic factors for OS (P<0.05 for all). Multivariate analysis showed that lack of PR expression, T stage ≥2, and positive axillary lymph node metastasis were independent risk factors for poor DFS and OS in ER-positive breast cancer patients (P<0.05 for all). Subgroup analysis showed that lack of PR expression was not significant in predicting poor DFS or OS when patients were in stage Ⅰ or with a small tumor (≤2 cm) (P>0.05 for all), and also showed that premenopausal women with PR-negative disease had poorer DFS and OS than PR-positive patients (P<0.05 for both). Lack of PR expression is an independent risk factor for poor prognosis in patients with operable ER-positive invasive breast cancer, especially in patients with a large tumor (>2 cm), advanced clinical stage (Stage Ⅱ or Ⅲ) or in premenopausal status.

An Increased Number of Perineural Invasions Is Independently Associated With Poor Survival of Patients With Resectable Pancreatic Ductal Adenocarcinoma.

The aim of this study was to investigate the impact of the number of perineural invasions (PNIs) in resected specimens on the survival of patients with pancreatic ductal adenocarcinoma (PDAC). A retrospective cohort study of 209 patients underwent surgical resection for PDAC between 1999 and 2013 was performed. The severity of PNI was evaluated by counting the number of PNIs in all sections with PDAC. The relationships of the number of PNIs with disease-free survival (DFS) and overall survival (OS) were analyzed. At least 1 PNI was observed in 197 (94%) of 209 patients. Significant differences in DFS and OS were found between groups when analyzed by the median number of PNIs (≥25 vs <25) (DFS: P < 0.0001; OS: P < 0.0001) and among tertiles greater than 40 versus 40 to 14 versus less than 14 (DFS: P < 0.0001, OS: P < 0.0001). By multivariate analysis, an increased number of PNIs (>40 vs 40-14 vs <14) was identified as an independent risk factor for poor DFS (P < 0.0001) and OS (P < 0.0001). The severity of PNI evaluated by counting the number of PNIs in resected specimens was useful for predicting the prognosis of patients with resectable PDAC.

VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma.

PurposeThe purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC).Materials and MethodsA total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS).ResultsIn univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS.ConclusionHigh expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

Mo1574 Prognostic Impact of Human Equilibrative Nucleoside Transporter 1 and Ribonucleotid Reductase Submit 1 Expression in Cholangiocarcinoma Patients Treated With Adjuvant Gemcitabine-Based Chemotherapy

Background: The efficacy of AGC varies among individuals and the resulting survival rates are still unsatisfactory. Objective: The aim of this study was to investigate predictive value of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotid reductase submit 1 (RRM1) expression for advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. Methods: Intratumoral hENT1 and RRM1 expression was investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (including 68 with AGC, and 59 without AGC). Impact of hENT1 and RRM1 expression on diseasefree survival (DFS) and overall survival (OS) were evaluated by univariate and multivariate analyses. Results: High intratumoral hENT1 and RRM1 expression was observed in 86 (68%) and 67 (53%) patients, respectively. Univariate analysis of data from 68 patients with AGC revealed that high hENT1 and low RRM1 expression were significantly associated with longer DFS (hENT1, P = 0.005; RRM1, P = 0.015) and longer OS (hENT1, P = 0.036; RRM1, P = 0.035). In multivariate analysis, moderately or poorly differentiation, (P = 0.007), low hENT1expression (P = 0.044) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor DFS, and moderately or poorly differentiation, (P = 0.045), lymph node metastasis, (P = 0.011) and high RRM1 expression (P = 0.009) were identified as independent risk factors for poor OS. In contrast, hENT1 and RRM1 expression did not correlate with DFS and OS in 58 patients without AGC. Conclusions: Intratumoral hENT1 and RRM1 expression predicts survival of advanced cholangiocarcinoma patients treated with AGC.

Alcohol consumption and recurrence of non-B or non-C hepatocellular carcinoma after hepatectomy: a propensity score analysis

The aim of this study was to identify factors related to the recurrence of non-B or non-C (NBNC) hepatocellular carcinoma (HCC). Between April 2000 and March 2012, out of 621 consecutive HCC patients at our institution, 543 who underwent initial hepatectomy and had no extrahepatic metastases were enrolled in the study. Multivariate analysis were performed to identify risk factors for poor disease-free survival (DFS). The 5-year DFS rate of NBNC (34 %) was better than that of hepatitis virus B (30 %, P = 0.011) and hepatitis virus C (21 %, P < 0.0001), significantly. Multivariate analysis revealed NBNC [hazard ratio (HR), 0.5; 95 % CI, 0.4-0.8; P < 0.0001)] to be an independent factor for DFS rate. We constructed a propensity score matching model with the 543 patients, and the 5-year DFS rates with and without severe alcohol liver disease (ALD) were 31.6 and 47.5 %, respectively (P = 0.013). In the 163 NBNC patients, severe ALD, mild ALD, and no ALD were seen in 35, 56, and 72 patients, respectively. Multivariate analysis revealed a vascular invasion into the hepatic vein (HR, 3.3; 95 % CI, 1.7-6.3; P < 0.0001) and severe ALD (HR, 2.0; 95 % CI, 1.1-3.6; P = 0.020) to be independent risk factors for poor DFS. By propensity score matching between mild and severe ALD, the 5-year DFS rates with severe and mild ALD were 26 and 50 %, respectively (P = 0.035). The prognoses of NBNC patients were better than those of patients with viral infections. Among the NBNC patients, preoperative excessive alcohol intake decreased DFS rate of HCC occurrence after surgery.