Lymphoid Metastasis Research Articles

Exploring the Protective Role of Aspirin Use in Mitigating Colorectal Cancer (CRC) Metastasis: A Nationwide Analysis (2016 to 2020).

Despite advancements in treatment strategies, the mortality from colorectal cancer (CRC) remains high. Evidence suggests that aspirin (ASA) may have a protective effect on CRC incidence and metastasis through various mechanisms. The 2016 to 2020 National Inpatient Sample was used to identify adult patients (age above 18y) with the principal diagnosis of CRC. Patients were stratified into 2 groups based on ASA use. The outcomes studied were in-hospital mortality and rates of total, gastrointestinal (GI), non-GI, and lymphoid metastasis. A multivariate logistic regression analysis was performed to evaluate the impact of ASA use on outcomes after adjusting for patient demographics, comorbidities, and the Elixhauser Comorbidity Index (ECI). Of the 814,270 patients, 88,620 (10.8%) used ASA, with the majority being aged above 65 years (78%), male (57%), white (77.6%), and had Medicare insurance (74.5%). There was a higher prevalence of Diabetes mellitus, Hypertension, Chronic pulmonary disease, Coronary artery disease, Chronic kidney disease, Chronic heart failure, Obesity, and Smoking among aspirin users than among non-ASA users. Patients who used ASA had a lower prevalence of total (47.3% vs. 32.5%, P<0.001), GI (22.2% vs. 32.4%, P<0.001), non-GI (9.9% vs. 15.3%, P<0.001), and lymphoid (9.3% vs. 10.9%, P<0.001) metastasis compared with those who did not use ASA. After adjusting for confounding factors, patients with ASA use had lower odds of total (aOR: 0.75, 95% CI: 0.72-0.78, P<0.001), GI (aOR: 0.74, 95% CI: 0.71-0.77, P<0.001), non-GI (aOR: 0.72, 95% CI: 0.68-0.77, P<0.1), and statistically insignificant odds of lymphoid (aOR: 0.95, 95% CI: 0.90-1.00, P=0.098) metastasis. The use of ASA is associated with a decrease in the prevalence of metastasis among individuals diagnosed with CRC, but additional studies are required to elucidate the mechanism and duration of therapy needed to be effective.

Impact of aspirin use on rates of metastasis in patients with esophageal cancer: insights from the National Inpatient Sample.

Despite advancing treatment methods, esophageal cancer (EC) maintains a high mortality rate and poor prognosis. Through various mechanisms, aspirin has been suggested to have a chemopreventive effect on EC. However, the long-term impact, particularly regarding the rate of metastasis, needs to be further elucidated. NIS 2016-2020 was used to identify adult patients (age > 18years) with EC using ICD-10 codes. Patients with missing demographics and mortality were excluded. Patients were stratified into two groups based on aspirin use. Data were collected on patient demographics, Elixhauser Comorbidity Index (ECI), and comorbidities (hypertension, chronic pulmonary disease, coronary artery disease (CAD), chronic kidney disease (CKD), congestive heart failure (CHF), coagulopathy, alcohol use, smoking, and obesity). The outcomes studied were rates of total metastasis, gastrointestinal (GI) metastasis, non-GI metastasis, and lymphoid metastasis. Multivariate logistic regression analysis was performed to evaluate the impact of aspirin use on various metastases after adjusting for patient demographics, comorbidities, and ECI. Out of 190,655 patients, 20,650 (10.8%) patients were aspirin users. Majority of the patients in the aspirin group were aged > 65years (74.7%), males (82.1%), White race (84%), and had medicare insurance (71%). There was a higher incidence of diabetes, hypertension, chronic pulmonary disease, CAD, CKD, CHF, and smoking in aspirin users than non-aspirin users. Patients with aspirin users had a lower incidence of metastasis (28.9% vs. 38.7%, P < 0.001), GI metastasis (14.2% vs. 20.6%, P < 0.001), non-GI metastasis (15.1% vs. 22%, P < 0.001), and lymphoid metastasis (8.9% vs. 11.3%, P < 0.001) than non-aspirin users. After adjusting for confounding factors, patients with aspirin use had lower odds of having metastasis (aOR-0.73, 95% CI-0.70-0.77, P < 0.001). Our study noted that aspirin use is associated with a reduction in the rate of metastasis in patients with EC. These studies support the use of aspirin in patients with EC and suggest the need for further studies to understand the mechanism by which aspirin use reduces metastasis in patients with EC.

A RARE CASE OF ADRENAL GANGLIONEUROBLASTOMA WITH METASTASIZED LYMPH NODE IN A YOUNG ADULT

Adrenal ganglioneuroblastoma is an extremely rare tumor among adrenal neoplasms in adult. We reported a 26-year-old young female patient presented with vague pain in left plank. Abdominal sonography and CTScan revealed a heterogenous solid lobulated left adrenal mass which contenting central necrosis, hemorrhage, coarse calcification and multiple adjacent metastasized lymphoid nodules, hence adrenal cortical carcinoma was not excluded although testing for adrenal function were normal. The patient was performed left adrenal surgery following by chemical therapy. Histiology was consistent with intermixed stroma-rich ganglioneuroblastoma. In literature, about 20 cases of adrenal ganglioneuroblastoma in adults were described, in which lymphoid metastasis was uncommon. Therefore, although adrenal ganglioneuroblastoma is obtained by histiology, imaging features should be invested further to differentiate from other neoplasms for appropriate treatment.

Effects of the CRYAB gene on stem cell-like properties of colorectal cancer and its mechanism.

Alpha B-crystallin (CRYAB), a known molecular chaperone, is involved in the occurrence and development of various tumor types. However, the function of CRYAB in colorectal cancer stem cells (CSCs) remains unknown. This study aimed to elucidate the role and possible regulatory mechanisms of CRYAB in the cancer stem cell-like phenotype of colorectal cancer (CRC). The expression of CRYAB in patients with CRC and lymph node metastasis at various stages and its relationship with overall survival were detected using the TCGA database. In this study, CRC-CSCs were enriched from HCT116 and Caco2 cells with serum-free suspension culture. The CRYAB gene, stemness-related genes, and mesenchymal markers were detected via quantitative real-time PCR (qRT-PCR) in CRC cells. Then, CRYAB-HCT116S and CRYAB-Caco2S cell lines were established by lentivirus-mediated overexpression of CRYAB. Self-renewal ability and stemness features were measured by the sphere formation assay and flow cytometry. The tumorigenesis capacity in vivo was inspected in nude mice. The functions of CRYAB on CSC proliferation, migration, and invasion were examined using colony formation and the transwell assay. Finally, the Wnt/β-catenin pathway-related mRNAs and proteins were detected via qRT-PCR and western blotting. The expression of CRYAB in CRC is related to the clinical phase and prognosis, except with lymphoid metastasis. CRYAB expression was elevated in CSCs. Upregulation of CRYAB enhanced the expression of CSC-related genes and mesenchymal markers. The capacity to form colonospheres, tumorigenesis, cell proliferation, and metastasis were significantly advanced in CRYAB-overexpressed cells. Moreover, CRYAB dramatically suppressed β-catenin degradation and downregulated the expression of p-GSK-3β. CRYAB maintains CSC formation via the Wnt/β-catenin pathway in CRCs, which may, therefore, function as vital molecular targets for CRC therapeutic strategies.

MiR-657 Targets SRCIN1 via the Slug Pathway to Promote NSCLC Tumor Growth and EMT Induction.

Background MicroRNA- (miR-) 657 has been shown to regulate immunological and inflammatory activity, and it has also been defined to be dysregulated in both non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma. The mechanistic role whereby miR-657 influences NSCLC progression, however, has yet to be clarified. Methods miR-657 and SRCIN1 expression levels were assessed via qPCR in the cell lines and tissues of NSCLC. Besides, correlations between the levels of miR-657 and NSCLC patient pathological characteristics were examined, and the Kaplan-Meier approach was employed for the evaluation of the prognostic utility of miR-657 in these patients. Moreover, the Pearson correlation analyses and dual-luciferase reporter assessments were used for detecting interactive relationships between miR-657 and SRCIN1. In addition, CCK-8, EdU, and Transwell assessments were employed for the appraisal of the ability of miR-657/SRCIN1 to regulate NSCLC cell proliferation and invasion. Western blotting was employed for the assessment of the levels of NSCLC cell proteins associated with the epithelial-mesenchymal transition (EMT) that were influenced by miR-657. The nude mice xenograft tumor model is established to observe the effect of miR-657 on NSCLC growth in vivo. Results NSCLC patient tissues and cell lines exhibited upregulated miR-657 expression that was closely related to tumor differentiation, lymphoid metastasis, and TNM stage. High levels of miR-657 were predictive of a poorer NSCLC patient prognosis, and overexpressing miR-657 resulted in the more rapid growth of NCI-H1650 and A549 cells, with a concomitant increase in their invasion. In addition, miR-657 overexpression raised the levels of Slug, N-cadherin, and Vimentin in these two cell lines while promoting E-cadherin downregulation. Dual-luciferase reporter assays confirmed that miR-657 was capable of binding to the SRCIN1 gene, and SRCIN1 expression levels were negatively associated with those of miR-657, indicating that it acts as a negative regulator of this gene. Knocking down SRCIN1 was capable to reverse the influences of miR-657 inhibitor treatment on NSCLC cell behavior. Finally, in vivo studies showed that miR-657 promoted NSCLC cell growth. Conclusion The obtained findings illuminate that miR-657 can promote the growth of tumors and the induction of the EMT in NSCLC cells by targeting SRCIN1 expression and modulating Slug pathway activation, highlighting this pathway as a promising therapeutic target in cases suffering from NSCLC.

A clinical analysis of oropharyngeal squamous cell carcinoma: a single-institution's experience.

We herein report the treatment outcome of oropharyngeal squamous cell carcinoma (OPSCC) at Kyushu University Hospital, the total number of OPSCC cases, and changes in the proportion of human papilloma virus (HPV)-related carcinomas over time. We performed a retrospective analysis of 237 cases treated for OPSCC at Kyushu University Hospital between 2013 and 2019. We performed HPV-mRNA in situ hybridization and p16 immunohistochemistry. This study included 197 males (82.1%) and 40 females (17.9%). The disease-specific, progression-free and overall survival (OS) were 69%, 62% and 61%, respectively, over the decade-long study period. p16-Immunohistochemistory and highrisk HPV mRNA in situ hybridization were positive in 114 (48.1%) and 105 (44.3%) cases, respectively. The number of HPV-related OPSCC cases increased according to an annual analysis. HPV+ cases had a significantly better prognosis than HPV- cases. In addition, p16+/HPV- cases had a significantly worse prognosis than p16+/HPV+ cases (OS: p = 0.0484). HPV+ OPSCC cases were associated with a younger age (< 60years old) (p = 0.0429), non-smoker (p = 0.0001), lateral tumor site (< 0.00001), lymphoid metastasis (< 0.0001) and low clinical stage (< 0.0001). The frequency of HPV-related OPSCC cases is increasing in Japan as well as worldwide, and such cases are characterized by no smoking habit, a young age, and a good prognosis. Even in p16+ OPSCC, HPV- cases had a poor prognosis, suggesting the importance of accurate HPV determination. To determine the intensity of treatment for HPV-related and non-related OPSCC, it is necessary to accumulate cases for the accurate HPV determination and comparison of treatment effects.

Clinicopathological and Prognostic Significance of Immunoscore and PD-L1 in Intrahepatic Cholangiocarcinoma.

BackgroundAn increasing amount of evidence reveals that immunosuppression is a major issue in cancer progression. The association of immunoscore (IS) and its impact on clinical outcome have been studied in many tumor types, but its significance in intrahepatic cholangiocarcinoma (ICC) is poorly known.MethodsBy immunohistochemistry, CD3 and CD8 expressions were assessed in tissue samples of 50 cases of postoperative ICC. The IS was determined by analyzing CD3+ and CD8+ expression data in different areas (intratumor and invasion margins). The relationship between IS and clinicopathological characteristics, including the overall survival (OS) and recurrence-free survival (RFS), was analyzed. In addition, PD-L1, a major regulator of immune escape, was also assessed in tumor cells by immunohistochemistry.ResultsIS was related to histological differentiation (P=0.026), the presence of lymphoid metastasis (P=0.034), and TNM clinical stages (P = 0.031) of ICC. High IS was significantly associated with better RFS (P=0.033) and OS (P=0.014). IS was an independent prognostic factor for better OS in multivariate analysis. PD-L1 expression was closely related to tumor vascular invasion (P=0.044). Although there was no association between PD-L1 expression and IS, high PD-L1 expression in tumor cells indicated poor RFS (P=0.017) and OS (P=0.004) in ICC.ConclusionThe IS and PD-L1 may be used as a complement to the TNM system for predicting the prognosis of patients with ICC.

Adjuvant Transarterial chemoembolization does not influence recurrence-free or overall survival in patients with combined hepatocellular carcinoma and Cholangiocarcinoma after curative resection: a propensity score matching analysis

BackgroundThe prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.MethodsIn this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.ResultsA total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769–4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545–1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686–6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06).ConclusionsThe present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.

Africa calls: A phone-based training program aids a continent's rising stars: A 20-year-old distance learning project has helped to train a generation of African cytopathologists.

Africa calls: A phone-based training program aids a continent's rising stars: A 20-year-old distance learning project has helped to train a generation of African cytopathologists.

Heterogeneity of PTEN and PPAR-γ in cancer and their prognostic application to bladder cancer.

The aim of the present study was to determine the prognostic value of peroxisome proliferator-activated receptor-γ (PPAR-γ) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) for bladder cancer. Data were collected from The Cancer Genome Atlas (TCGA), a public database, and were analyzed to assess PTEN and PPAR-γ heterogeneity as well as distinct trends in bladder cancers. Furthermore, PPAR-γ and PTEN expression levels and their association with one another were evaluated. Finally, the prognostic significance of PPAR-γ and PTEN for bladder cancer was validated in vivo using clinical samples. Based on the TCGA database, PTEN levels were significantly increased in bladder cancers (P<0.001); whereas PPAR-γ expression was downregulated in the same samples (P<0.05). Furthermore, linear correlation analysis indicated that in bladder cancers, PPAR-γ and PTEN are inversely correlated (P<0.001). The assessment and analysis of clinical samples revealed that PPAR-γ was significantly elevated in tumor tissues (P<0.001); however, PTEN was downregulated in cancer tissues (P<0.001). Furthermore, PPAR-γ expression determined by immunohistochemistry grey level (P=0.002) was also elevated in high-grade and invasive bladder cancers compared with low-grade and superficial tumors, whereas PTEN levels exhibited the opposite in this analysis (P=0.001). In individuals with lymphoid metastasis, PPAR-γ was significantly increased (P<0.001), and PTEN was significantly decreased (P<0.001). Pearson analysis revealed a significant negative correlation between PPAR-γ and PTEN expression (r=-0.604, P<0.05). In conclusion, tissue heterogeneity was observed with respect to PPAR-γ and PTEN expression in bladder cancer. PTEN and PPAR-γ expression are negatively correlated and may be excellent indicators of bladder cancer tumorigenesis and progression.

Histopathology-based immunoscore predicts recurrence for intrahepatic cholangiocarcinoma after hepatectomy.

Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan-Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen's model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values.

Development and validation of a prognostic score predicting recurrence in resected combined hepatocellular cholangiocarcinoma.

Purpose: To develop and validate a decision aid to help make individualized estimates of tumor recurrence for patients with resected combined hepatocellular cholangiocarcinoma (CHC).Patients and methods: Risk factors of recurrence were identified in the derivation cohort of 208 patients who underwent liver resection between 1995 and 2014 at Zhongshan Hospital to develop a prediction score. The model was subsequently validated in an external cohort of 101 CHC patients using the C concordance statistic and net reclassification index (NRI).Results: On multivariate analysis, five independent predictors associated with tumor recurrence were identified, including sex, γ-glutamyl transferase, macrovascular invasion, hilar lymphoid metastasis and adjuvant transcatheter arterial chemoembolization. The prediction score was constructed using these 5 variables, with scores ranging from 0 to 5. A patient with a score of 0 had a predicted 1- and 5-year recurrence risk of 11.1% and 22.2%, respectively. In the validation cohort, the NRIs of prediction score vs American Joint Committee on Cancer 7th TNM staging system at 1-year and 5-year were 0.185 (95% CI, 0.090–0.279, P<0.001) and 0.425 (95% CI, 0.044–0.806, P=0.03), respectively.Conclusion: Our developed and validated prediction score might be a simple and reliable method in postoperative CHC patients and help clinicians identify candidates who may benefit from future adjuvant therapies.

Cognate Nonlytic Interactions between CD8+ T Cells and Breast Cancer Cells Induce Cancer Stem Cell-like Properties.

Targeting of tumor immune escape mechanisms holds enormous therapeutic potential. Still, most patients progress under immune checkpoint blockade and some even become hyperprogressors. To investigate how cancer cells respond to activated but ineffective T cells, we challenged peptide-loaded MCF-7 breast cancer cells with antigen-specific CD8+ T cells in which lytic granules had been destroyed by pretreatment with Concanamycin A. Gene expression analysis after coculture revealed simultaneous induction of PD-L1, IDO1, CEACAM1, and further immunoregulatory checkpoints in breast cancer cells. Strikingly, we further observed gene signatures characteristic for dedifferentiation and acquisition of pluripotency markers including Yamanaka factors. Cognate interaction with nonlytic CD8+ T cells also increased the proportion of stem cell-like cancer cells in a cell-to-cell contact- or (at least) proximity-dependent manner in various cell lines and in primary breast cancer cell cultures; this induction of stem cell-like properties was confirmed by enhanced tumor-forming capacity in immunodeficient mice. Resulting tumors were characterized by enhanced cell density, higher proliferation rates, and increased propensity for lymphoid metastasis. These findings describe a widely underappreciated pathway for immune escape, namely immune-mediated dedifferentiation of breast cancer cells, which is associated with profound changes in gene expression and cellular behavior. As the enhanced malignant potential of cancer cells after nonlytic cognate interactions with CD8+ T cells enables increased tumor growth and metastasis in BALB/cnu/nu mice, the described mechanism may provide a possible explanation for the clinical phenomenon of hyperprogression in response to unsuccessful immunotherapy. SIGNIFICANCE: This study shows that ineffective immune responses not only fail to clear a malignancy, but can also activate pathways in cancer cells that promote stemness and tumor-seeding capacity.

Relationship between expression of BRAFV600E and Ki67 protein and clinical pathologic characteristics of thyroid carcinoma

Objective To explore the relationship between BRAFV600E, Ki67 protein and thyroid carcinoma with different pathologic characteristics, thus to provide clinical evidence on early prognosis and personalized treatment in patients with thyroid carcinoma. Methods From January 2015 to January 2017, 76 patients diagnosed as papillary thyroid carcinoma(PTC), who treated in Yinzhou People's Hospital, were enrolled.Twenty cases with normal tumor-adjacent tissue after operation and 34 patients with non-PTC were also enrolled as control.All the patients enrolled were not treated with endocrine, chemical and radiotherapy.The expression of BRAFV600E and Ki67 protein was detected by immunohistochemical method, and the BRAFV600E and Ki67 expression and their correlation with different pathologic characteristic of thyroid carcinoma was analyzed by SPSS 18.0. Results The positive rate of BRAFV600E and Ki67 protein in 110 patients with thyroid carcinoma was 56.36%(62 cases) and 39.09%(43 cases), with the highest expression of BRAFV600E and the lowest expression of Ki67 in patients with PTC respectively.The expression of BRAFV600E and Ki67 protein was all negative in normal tumor-adjacent tissue.The positive expression of BRAFV600E and Ki67 in patients with PTC demonstrated significant difference in TNM stage, tumor side and lymphoid node metastasis(BRAFV600E: χ2=5.281, 9.771, 9.771, all P 0.05; Ki67: χ2=0.224, 0.518, 1.281, all P>0.05). Conclusion The detection of BRAFV600E and Ki67 is benefit on judging of innocent and malignant, the malignant degree of thyroid tissue.The high expression of BRAFV600E and Ki67 is benefit on differentiating PTC and early evaluation of prognosis. Key words: Thyroid neoplasms; Protein, BRAFV600E; Protein, Ki67

Fibrinogen Levels Are Associated with Lymph Node Involvement and Overall Survival in Gastric Cancer Patients.

Combination of perioperative chemotherapy with gastrectomy with D2 lymphadenectomy improves long-term survival in patients with gastric cancer. The aim of this study was to investigate the predictive value of preoperative levels of CRP, albumin, fibrinogen, neutrophil-to-lymphocyte ratio and routinely used tumor markers (CEA, CA 19-9, CA 72-4) for lymph node involvement. This retrospective study was conducted in 136 patients who underwent surgery between 2007 and 2015. Bivariable and multivariable analyses were performed in order to identify important characteristics associated with the risk of lymph node involvement. Kaplan-Meier survival curves and log-rank tests were used to compare overall survival. Lymph node involvement was significantly affected by preoperative fibrinogen (p=0.008) and albumin (p=0.023). Poor clinical condition, T and N staging and fibrinogen level above 3.5 g/l were significantly associated with worse overall survival. Preoperative fibrinogen and albumin levels are significantly associated with lymphoid metastases in patients with gastric cancer.

Surgical Treatment of Combined Hepatocellular-Cholangiocarcinoma is as Effective in Elderly Patients as it is in Younger Patients: A Propensity Score Matching Analysis.

Aims: To compare the long-term prognosis of younger and elderly patients with combined hepatocellular-cholangiocarcinoma (CHC) who underwent curative resection between 1993 and 2014 at our center.Methods: Two hundred and thirteen patients who underwent liver resection for CHC were enrolled in our study. The overall survival (OS) and disease-free survival (DFS) of elderly patients (age≥60, n=52) and younger patients (age<60, n=161) were compared by multivariate analysis and propensity score matching (PSM) analysis.Results: Among the 213 CHC patients, the elderly patients had a higher rate of worse Child-Pugh grade (P=0.027), abnormal serum albumin (P<0.001) and lymphoid metastases (P=0.024). The proportion of HBV-positive CHC patients (74.6%, 159/213) was much higher than that observed in healthy cohorts. Younger patients had a higher rate of hepatitis B virus (HBV) infection compared to older patients (83.9% vs 46.2%, P<0.001). OS and DFS of the elderly and younger patients before and after propensity score matching were comparable.Conclusion: Elderly and younger patients who underwent liver resection for CHC have comparable long-term OS and DFS.

Validation of TNM classification for metastatic prostatic cancer treated using primary androgen deprivation therapy.

e604 Background: The current tumor–node–metastasis (TNM) classification system has been used for many years. The prognosis of patients with metastatic prostate cancer (mPC) treated using primary androgen deprivation therapy (PADT) was analyzed according to the TNM classification. Methods: A total of 5,618 cases with lymph node metastases only (N1M0), non-regional lymph node metastasis (M1a), bone metastasis (M1b), and distant metastasis (M1c) were selected from the Japanese Study Group of Prostate Cancer database. Overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) rates were calculated using Kaplan–Meier analysis. The influence of clinical variables on patient prognosis was evaluated using the Cox’s proportional hazard regression model. Results: Regarding age, patients with M1b tumors were significantly older than were those in the other groups. Prostate-specific antigen (PSA) levels tended to increase as the stage progressed. The Gleason score (GS) was significantly higher in the M1a group compared with the other groups. The 5-year OS was 76.0 % in the N1M0, 57.5 % in M1a, 54.0 % in M1b, and 40.0 % in M1c cases. The 5-year CSS was 83.2 % in the N1M0, 69.0 % in M1a, 63.1 % in M1b, and 51.5 % in M1c cases. The 5-year PFS was 38.8 % in the N1M0, 23.0 % in M1a, 23.0 % in M1b, and 16.6 % in M1c cases. OS, CSS, and PFS declined as the stage progressed; however, there were no statistically significant differences between M1a and M1b cases. Among the patients in the M1b group, the 2,445 cases of N0M1b and the 1,607 cases of N1M1b were compared. OS, CSS and PFS were all significantly worse in N1M1b compared with N0M1b. Multivariate analysis revealed that OS and CSS were worse in patients with a GS ≥ 8, and that combined androgen blockade (CAB) treatment provided better OS than non-CAB treatments at any tumor stage. However, OS and CSS were worse in individuals with a PSA &gt; 100 ng/ml only in M1b. Conclusions: Patient prognosis worsened with stage progression. Each PC cell that develops bone or lymphoid metastasis may exhibit different characteristics. CAB is recommended as the primary treatment for mPC.

ZNF23 Suppresses Cutaneous Melanoma Cell Malignancy via Mitochondria-Dependent Pathway

Background/Aims: Cutaneous melanoma is one of the leading causes of cancer deaths with an increasing incidence worldwide. A KRAB-containing zinc finger protein member, zinc finger 23 (ZNF23), was reduced in some types of tumors and inhibited cell growth by inducing cell cycle arrest. However, the role of ZNF23 expression is still poorly understood in melanoma. Methods: The level of ZNF23 expression was detected in cutaneous melanoma, adjacent normal skin tissues and cutaneous melanoma cell lines using immunohistochemistry and western blotting. The correlations between ZNF23 expression and other clinicopathologic parameters were analyzed in melanoma patients. Ectopic expression of ZNF23 plasmid was transfected into melanoma cells, SK-MEL-1 and SK-MEL-28. MTT, flow cytometry and transwell assay were used to measure cell proliferation, apoptosis, invasion and migration abilities, respectively. Mitochondrial functions and structures were detected by mitochondrial membrane potential assay and Transmission electron microscopy (TEM) method in melanoma cells transfected with overexpressing ZNF23 plasmid or empty vector. Western blotting was performed to detect the levels of ZNF23, p53, p27, Bcl-2 and cleaved caspase-3 after overexpressing of ZNF23 in melanoma cells. Results: ZNF23 was elevated in adjacent normal skin tissues compared with melanoma tissues. Patients with low level of ZNF23 expression exhibited higher incidence of lymphoid metastasis, thicker size of tumors and worse outcome. By using Cox’s regression analysis, ZNF23 expression, tumor thickness and lymph node metastasis were the independent prognostic factors for overall survival (p < 0.05). Results from cellular experiments indicated that ectopic expression of ZNF23 induced cell apoptosis by activation of caspase-3, p27, p53 expression and down-regulation of Bcl-2 through mitochondria-dependent pathway. Conclusions: Decreased ZNF23 was contributed to melanoma progression and poor survival with mitochondria-dependent pathway. It indicated that ZNF23 could be a promising therapeutic biomarker candidate for cutaneous melanoma.

Pim-3 is a Critical Risk Factor in Development and Prognosis of Prostate Cancer.

BackgroundPim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer.Material/MethodsWe collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines.ResultsWe found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery.ConclusionsPim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese.

Histopathologically TTF-1 and Calcitonin Positive Laryngeal Typical Carcinoid Tumor with Elevated Serum Calcitonin

Even with 1% of the incidence, laryngeal neuroendocrine tumors are the second common tumors in larynx; as a subtype, typical carcinoid tumors are extremely rare. We presented a case of laryngeal typical carcinoid tumor and we discussed diagnostic criteria and treatment of these tumors. A 57-year-old male with a 3 months history of hoarseness was examined endoscopically and a laryngeal mass on left supraglottic area was seen. High levels of serum calcitonin were detected. The histopathological analysis of biopsy material was typical carcinoid tumor. Laryngeal tumor resection and left neck dissection were performed. The histopathologic result was TTF 1 and calcitonin positive primer laryngeal typical carcinoid tumor with cervical lymphoid metastasis. Serum calcitonin level returned to normal levels postoperatively. The distinction between laryngeal carcinoid tumors and metastasis of thyroid medullary carcinoma are difficult histopathologically. So, laryngeal carcinoid tumors should be kept in mind in these circumstances.