Mean Survival Time Of Patients Research Articles

Expression of c-Src and phospho-Src in epithelial ovarian carcinoma

Abnormal c-Src expression and activation has been observed in a number of tumors. To determine the therapeutic potential of Src inhibitors for ovarian cancer patients, this study aimed to explore the expression patterns of c-Src and phospho-Src in epithelial ovarian cancer. A total of 82 patients with epithelial ovarian cancer treated at Sun Yat-sen University Cancer Center from January 1999 to December 2005 were enrolled along with 25 patients with benign ovarian lesions; 20 normal ovarian tissues served as controls. Expression of c-Src and phospho-Src (Tyr416) was examined using immunohistochemistry. Survival analyses were performed using Kaplan-Meier curves. As compared to the control group, a significantly greater proportion of ovarian cancer tissues were positive for c-Src and phospho-Src expression (P < 0.001). c-Src expression was associated with age, while phospho-Src expression was significantly associated with age, FIGO stage, histology grade, and residual tumor size after surgery (all P < 0.05). The mean survival time was associated with phospho-Src expression, but not with c-Src expression. The mean survival times of patients with phospho-Src-positive tumors were significantly greater than those with phospho-Src-negative tumors (87.4 months, 95 % CI = 74.3-100.5 months and 91.5 months, 95 % CI = 84.7-98.2 months, respectively; P = 0.013). The increased c-Src expression and activation in epithelial ovarian cancer suggests that ovarian cancer patients may benefit from tyrosine kinase inhibitors such as Dasatinib. Activation of c-Src through phosphorylation at Tyr416 may play a role in the early stages of ovarian cancer development, and evaluation of its expression may be a useful prognostic marker of epithelial ovarian cancer.

Ten-Year Survivorship After Knee Arthroscopy in Patients With Kellgren-Lawrence Grade 3 and Grade 4 Osteoarthritis of the Knee

The purpose of this study was to document 10-year outcomes and total knee arthroplasty (TKA) rate after arthroscopic treatment of knee osteoarthritis and compare survivorship of patients with Kellgren-Lawrence (KL) grade 3 and 4 knees. Eighty-one knees in 73 patients (49 male, 32 female; mean age, 58 years; range, 37 to 79 years) that underwent an arthroscopic regimen for knee osteoarthritis between August 2000 and November 2001 were included in this institutional review board-approved study. The inclusion criterion was Kellgren-Lawrence (KL) grade 3 or 4 radiographic changes. A TKA had been recommended to all patients; however, none wished to undergo arthroplasty. All patients underwent arthroscopic treatment. Endpoint was defined as TKA for survivorship analysis. Outcomes were collected at a minimum follow-up of 10 years (Lysholm, Tegner, patient satisfaction, and WOMAC scores). Of 81 knees, 7 were in patients who died and 2 in patients who refused to participate, leaving 72 knees available for follow-up. Follow-up was obtained for 95% of patients (n= 69). Forty-three knees (62%) were converted to TKA at a mean of 4.4 years (range 1.0 to 9.6) after index arthroscopy. Mean survival time was 6.8 years (95% confidence interval [CI], 5.9 to 7.6 years). Survivorship was 60% at 5 years and 40% at 10 years. Patients with KL grade 4 osteoarthritis were 5.3 times more likely to fail (95% CI, 1.3 to 23.4) than those with KL grade 3 (P= .012). Mean survival time for patients with KL grade 4 was 5.7 years (95% CI, 4.5 to 6.9), and mean survival time for those with KL grade 3 was 7.5 years (95% CI, 6.2 to 8.7) (P= .022). For 26 knees that did not undergo arthroplasty, the mean Lysholm score was 74 (95% CI, 67 to 80), the median Tegner activity scale score was 3 (range, 0 to 8), the median patient satisfaction with outcome was 9 (range, 1 to 10), and the mean WOMAC score was 18.5 (95% CI, 13 to 24) at 10 years of follow-up. The mean survival time after arthroscopic treatment of osteoarthritis with a defined protocol was 6.8 years. Forty percent delayed arthroplasty for a minimum of 10 years. Patients with KL grade 4 changes in their knee had a higher risk of conversion to arthroplasty and a significantly lower mean survival time. Level III, retrospective comparative study.

High YKL-40 Serum Concentration Is Correlated with Prognosis of Chinese Patients with Breast Cancer

This study aimed to investigate the association between serum YKL-40 and prognosis of breast cancer in a Chinese population. Expression of YKL-40 of 120 Chinese patients with breast cancer and 30 controls (benign breast lesions) was measured in tumor tissue by immunohistochemistry and in serum by ELISA. Differences in YKL-40 positivity grouped by specific patients’ characteristics were compared using Pearson Chi-square test for rates of intratumoral staining, one-way ANOVA with a Bonferroni post-hoc comparison, or two-sample t-test for mean YKL-40 serum concentrations. Factors associated with overall survival were identified by univariate and multivariate cox-regression analyses. YKL-40 was elevated in approximately 75% of Chinese patients with breast cancer. A significantly higher percentage of patients with YKL-40 positive tumors had larger tumor size, higher TNM stage, and/or lymph node metastasis. Significantly higher mean YKL-40 serum concentrations were observed in patient subgroups with invasive lobular carcinoma (P<0.0167), higher TNM stage (P<0.001), and positive lymph node metastasis (P<0.001). The estimated mean survival time of patients with YKL-40 positive tumors was significantly shorter than for patients with YKL-40 negative tumors (55.13 months vs 65.78 months, P = 0.017). Multivariable Cox-regression analysis identified a significant association of overall survival time with YKL-40 serum concentration. Patients with YKL-40 positive tumors had significantly shorter disease free survival times than those with YKL-40 negative tumors. We propose that the potential utility of YKL-40 intratumoral staining or serum concentration as a biomarker for breast cancer is greatest within 5 years of diagnosis.

Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma

To evaluate and characterize macrophage populations (M1/M2) in the tumor microenvironment of oral cavity squamous cell carcinoma (OCSCC). The relationship between macrophages and clinicopathological factors, such as survival data, lymph node metastasis, tumoral proliferation, and WHO histological grading are also analyzed. The samples consisted of surgically excised specimens from patients with non-metastatic and metastatic OCSCC and normal oral mucosa (control). Immunohistochemistry, flow cytometry, and qRT-PCR were used to evaluate macrophage populations and the expression of pro- (IL-12, IL-23, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines. The level required for statistical significance was defined as p<0.05. The data showed a predominance of M2 phenotype (high percentage of IL-10(+)TGF-β(+)) macrophages in the tumor microenvironment of OCSCC. A higher percentage of macrophages expressing TGF-β was seen in the OCSCC group when compared with healthy individuals. The assessment of mRNA expression also presented a greater expression of anti-inflammatory cytokines TGFβ and IL10 in OCSCC when compared with the control group. The percentage of macrophages, demonstrated by immunohistochemistry, was significantly higher in the metastatic OCSCC group than in the non-metastatic and control groups. The log-rank test also showed that the mean survival time for patients with high levels of macrophages was less (44 months) when compared with patients with a low percentage of such cells (93 months). A predominance of the M2 phenotype in the tumor microenvironment of OCSCC could contribute to local immunosuppression, via TGF-β production, and consequently greater lymph node involvement and reduced patient survival time.

Expression of p130cas, E-cadherin and β-catenin and their correlation with clinicopathological parameters in non-small cell lung cancer: p130cas over-expression predicts poor prognosis

p130cas (p130 Crk-associated substrate) is a scaffolding protein and plays an important role in regulating focal adhesion and driving cell migration. Also, the destruction of E-cadherin/β-catenin adhesive complex is one of the changes that characterizes the invasive phenotype of tumors. The aim of this study is to evaluate the role of p130cas, E-cadherin, and β-catenin expression in patients with non-small cell lung cancer (NSCLC). We examined the expression of p130cas, E-cadherin, and β-catenin in 105 lung cancer tissues and paired adjacent normal lung tissues using immunohistochemistry. The overexpression of p130cas was observed in 61.9% (65/105) of lung cancer samples. The overexpression of p130cas was correlated with abnormal expression of E-cadherin and β-catenin (P=0.002 and P=0.006, respectively). Chi-square test showed that the overexpression of p130cas correlated positively with lymph node metastasis and high TNM stage. The Log-Rank test revealed that the mean survival time of patients with p130cas overexpression (36.31 ± 5.66 months) was markedly shorter than those with p130cas normal expression (60.57 ± 6.95 months). Multivariable analysis indicated p130cas overexpression (P<0.001) as an independent significant prognostic factor for NSCLC patients' survival. These results indicate that p130cas may impact a variety of clinicopathological features of NSCLC and may y influence the prognosis of lung cancer patients.

Tumor microRNA-335 expression is associated with poor prognosis in human glioma

MicroRNA-335 (miR-335), as a transcript of genomic region chromosome 7q32.2, acts as a tumor suppressor or tumor promoter in various human malignancies. Especially, it has been reportedly shown to be an oncogene in human glioma cell line in vitro, but its expression in human glioma tissues is not yet determined. The aim of this study was to investigate the clinical significance of miR-335 expression in glioma. MiR-335 expression in human gliomas and nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay. The association of miR-335 expression with clinicopathological factors and prognosis of glioma patients was statistically analyzed. The expression level of miR-335 in glioma tissues was significantly higher than that in corresponding nonneoplastic brain tissues (P < 0.001). In addition, high miR-335 expression was significantly associated with a higher WHO grade (P = 0.001). Survival analysis demonstrated that patients with high miR-335 expression tumors had significantly shorter survival times than those with low miR-335 expression tumors (P = 0.01) and that miR-335 was an independent prognostic factor (P = 0.02). Especially, subgroup analyses according to tumor histologic grade revealed that the mean survival time of patients with high grade (III-IV) was significantly worse for high miR-335 expression group than for low miR-335 expression group (P = 0.002), but no significant difference was found for patients with WHO grade I-II (P = 0.16). These results indicated that miR-335 expression was increased in human gliomas and was associated with advanced tumor progression. Furthermore, miR-335 expression was demonstrated for the first time to be an independent marker for predicting the clinical outcome of patients with gliomas.

Abstract 1220: ErbB4: A novel therapeutic target in glioblastoma multiforme

Abstract Introduction: Glioblastoma Multiforme or glioma is amongst the most lethal and difficult to cancers to treat and kills 1,000 Australians and 12,000 Americans every year. The average age at diagnosis is 60 years and the death rate for glioma has remained relatively unchanged for the past 20 years; highlighting the need for new therapeutic options for its treatment. ErbB4, the fourth member of the EGFR family has both oncogenic and tumor suppressive activity dependent upon isoform expression and although ErbB4 is universally expressed in glioma, its functional role is somewhat unclear. Aims: The aim of this study was to characterize the expression of ErbB4 in a large cohort of glioma tissues at the protein and mRNA level and determine if ErbB4 expression relates to tumor biology and patient survival. Methods: Immunohistochemistry was performed on paraffin sections of glioma tissue (n=68) and normal brain (n=5) for the immunolocalisation of ErbB4 and EGFR (total and activated) and the ErbB4 ligand heregulin. Using a customized RT-qPCR assay, ErbB4 isoforms were identified in snap frozen glioma (n=23) and normal brain (n=15). Results: Patients diagnosed with glioma (n=68) had a median survival time of 15 months (range 1-120 months) with the average age of 63±2 years (range 21-80 years). ErbB4 and heregulin protein was demonstrated in all our glioma and normal brain samples. At the mRNA level however, ErbB4 expression was reduced in the glioma samples when compared to normal brain tissue. All six ErbB4 isoforms were demonstrated in all tissue samples and ErbB4 was preferentially expressed as the JMa/Cyt2 isoform in glioma. Histologically, ErbB4 activation (independent of EGFR activation) occurred in 16% of patient samples and was localized to sites like the leading edge of the tumor. The mean survival time for patients with high levels of activated ErbB4 was 12 months, while patients with low levels of activated ErbB4 had a mean survival time of 32 months. ErbB4, activated ErbB4 and heregulin were also demonstrated in the vasculature of the glioma but not normal brain. Conclusions: This study demonstrated the preferential expression of the JMa/Cyt-2 isoform of ErbB4 in glioma along with increased ErbB4 activation significantly shortening patient survival times. Due to a potential angiogenic role of ErbB4 in glioma and reduced patient survival times following ErbB4 activation, ErbB4 should be considered a new therapeutic target in glioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1220. doi:1538-7445.AM2012-1220

Detection of a Point Mutation at Codon 12 of the Kirsten-Ras (K-ras) Oncogen in Myelodysplastic Syndrome

Background: Mutations in ras geneshave been observed in a variety of cancersand were found to play an important role in human leukemogenesis and in preleukemic disease as myelodysplastic syndrome (MDS). The purpose of this study was to determine the prevalence of mutated K-ras oncogene in myelodysplastic syndrome (MDS); with a special emphasis on their possible role in affecting clinical status, relation to karyotypic pattern; response to therapeutic measures; its impact on the fate of the disease and overall survival. Subjects & methods: Detection of point mutation of Kirsten-ras (K-ras) gene in 30 patients suffering from myelodysplastic syndrome was carried out using quantitative enriched polymerase chain reaction (QEPCR) and was confirmed by sequencing. QEPCR is a two- stage PCR procedure with modified primers that enriches mutant alleles, via restriction endonuclease digestion of normal alleles and enables identification of one mutant allele among 100,000 normal alleles. Results: Activating mutations of the codon 12 of K-ras gene were detected in 7/30 (23.3%)cases of MDS, the most common mutation involved a substitution of aspartic acid forglycine (GGT→GAT). The incidence of K-ras mutations was found to be significantly associated with refractory anemia with excess blasts type II (RAEBII) and unclassified (UC) MDS than other subtypes (p=0.005), and was significantly associated with hypercellular bone marrow (p=0.04) showing marked dyserythropoitic changes. Furthermore, mutant K-ras gene was found to be significantly associated with abnormal karyotypes (p=0.04). Patients with mutated K-ras gene were significantly associated with either high or intermediate risk according to International Prognostic Scoring System (IPSS) (p=0.001). 6/7(85.7%) of those carrying the mutation showed poor response to treatment compared to non carriers with a statistical significant difference (p=0.009). Five out of eight (62.5%) patients who were transformed to AML carried the mutant K-ras gene, their subtypes were RAEB?? and unclassified MDS with abnormal cytogenetics mainly Monosomy 7. Overall survival was detected using Kaplan-Meiercurve and the mean survival time of patients who carried K-ras mutations were significantly lower than those without the mutation (Log rank test=12.7; p=0.0004). Conclusion: MDS patients bearing an mutated K-ras oncogene frequently showed poor response to treatment; leukemic progression of the disease and shorter overall survival, suggesting that an activated K-ras oncogene is a critical factor for prognostic evaluation; therapeutic decision and monitoring of response to treatment of MDS patients.

Change point estimation in monitoring survival time.

Precise identification of the time when a change in a hospital outcome has occurred enables clinical experts to search for a potential special cause more effectively. In this paper, we develop change point estimation methods for survival time of a clinical procedure in the presence of patient mix in a Bayesian framework. We apply Bayesian hierarchical models to formulate the change point where there exists a step change in the mean survival time of patients who underwent cardiac surgery. The data are right censored since the monitoring is conducted over a limited follow-up period. We capture the effect of risk factors prior to the surgery using a Weibull accelerated failure time regression model. Markov Chain Monte Carlo is used to obtain posterior distributions of the change point parameters including location and magnitude of changes and also corresponding probabilistic intervals and inferences. The performance of the Bayesian estimator is investigated through simulations and the result shows that precise estimates can be obtained when they are used in conjunction with the risk-adjusted survival time CUSUM control charts for different magnitude scenarios. The proposed estimator shows a better performance where a longer follow-up period, censoring time, is applied. In comparison with the alternative built-in CUSUM estimator, more accurate and precise estimates are obtained by the Bayesian estimator. These superiorities are enhanced when probability quantification, flexibility and generalizability of the Bayesian change point detection model are also considered.

Patient–prosthesis mismatch after transapical aortic valve implantation: Incidence and impact on survival

Transcatheter aortic valve implantation (TAVI) has become an important therapeutic option for high-risk patients with severe aortic valve stenosis. Patient-prosthesis mismatch (P-PM) is an important determinant of morbidity and mortality after open aortic valve replacement. The objective of our study was to evaluate P-PM incidence and its impact on survival in a large cohort of patients treated with TAVI. We retrospectively analyzed transesophageal echocardiographic data of 278 consecutive patients (Society of Thoracic Surgeons score 18.5 ± 15.3, age 80 ± 8 years) who underwent transapical TAVI with Edwards Sapien valves between April 2008 and March 2011. Effective orifice area was calculated using the continuity equation and indexed with body surface area (iEOA). P-PM was stratified as severe (iEOA < 0.65 cm(2)/cm(2)) and moderate (iEOA, 0.65-0.85 cm(2)/m(2)). Midterm survival (up to 30 months) was analyzed by Kaplan-Meier curves and log-rank tests. There was no P-PM in 181 (65.1%) patients; moderate P-PM was found in 76 (27.3%) patients and severe P-PM in 21 (7.6%). Thirty-day survival was 96.0%, 97.3%, and 90.5%. The 3-month survival was 91%, 90%, and 66%, respectively (P = .0013). Combination of severe P-PM with peak pressure gradients greater than 10 mm Hg further reduced the 3-month survival to 48%. Additionally, mean survival time in patients with an ejection fraction less than 50% was significantly shorter than in patients with an ejection fraction greater than 50% (20.8 ± 1.5 vs 24.1 ± 0.8 months; P = .027). P-PM is found in patients undergoing transapical TAVI. Severe mismatch is accompanied by high early mortality, especially when combined with increased pressure gradients.

Serum IL10, IL12 and circulating CD4+CD25high T regulatory cells in relation to long-term clinical outcome in head and neck squamous cell carcinoma patients

IL10, but not IL12 or T regulatory cells in the circulation of newly presenting, pre-treatment head and neck squamous cell carcinoma (HNSCC) patients, has been shown previously to be related to survival over a mean follow-up period of 15months. Here, we followed the same patients for a longer period to determine whether these associations change. Pre- and post-treatment serum IL10/IL12 and circulating T regs were measured using ELISA and flow cytometry respectively and were correlated with survival after a 33 month average follow-up in a cohort of newly presenting HNSCC patients (n=107), with cancers of the hypopharynx (n=16), larynx (n=36), oral cavity (n=21), oropharynx (n=25), sinonasal (n=4) or unknown origin (n=5). Although the mean survival time of patients with detectable levels of IL10 pre-treatment was lower (40.6 months) than that of those without detectable levels of IL10 (45.6 months), the difference was no longer significant, in contrast to earlier follow-up data. In conclusion, although serum levels of IL10 may be a prognostic indicator for HNSCC patients over the short-term, they become less significant as follow-up time increases.

Outcome of Laparoscopy-Assisted Gastrectomy vs. Open Gastrectomy for Gastric Cancer: A Retrospective Comparative Study

Laparoscopy-assisted gastrectomy is still controversial because of scant evidence of safety and feasibility. The objective of this study was to assess the feasibility of using the laparoscopy-assisted gastrectomy in treating gastric cancer and evaluate its outcome compared with conventional open gastrectomy. Between November 2005 and November 2007, 31 patients underwent laparoscopy-assisted gastrectomy and 95 patients underwent open gastrectomy for gastric cancer. Clinicopathological characteristics, total number of lymph nodes retrieved and overall survival were retrospectively compared between the two groups. No significant differences were found in the total number of retrieved lymph nodes (26.3±11.6 vs. 27.6±10.4) between the two groups. The mean follow-up and overall survival time after surgery was 30.8 (range 4-47) months and 40.9 months (95% confidence interval, 38.5-43.2 months), respectively. The mean survival time in patients of the laparoscopy-assisted gastrectomy group was 42.4 months vs. 40.3 months in patients of the open surgery alone group (p=0.457). A logistic regression model revealed that node invasion (hazard ratio 1.149, p<0.001) and serosal invasion (hazard ratio 4.623, p=0.044) were associated with overall survival of gastric cancer patients. Laparoscopy-assisted gastrectomy with D2 lymph node dissection is a safe and feasible procedure with adequate lymphadenectomy for the treatment of gastric cancer.

Assessment of endoscopic drainage with bUiary double stents for advanced malignant hilar biliary obstruction

Objective To evaluate the therapeutic effects of endoscopic biliary double stents for ad- vanced malignant hilar biliary obstruction. Methods From January 2007 to December 2010, double stents was attempted in 28 patients （15 men and 13 women, median age 66.4 years （44-88 years）, including 9 with Bismuth 11,8 with type ma,5 with type Ⅲb and 6 with type IV. A total of 23 consecutive patients （ 11 men and 12 women, median age 65.8 years （42-83 years） with malignant hilar obstruction undergoing a therapy with single stent were recruited as the control group, including 7 with Bismuth Ⅱ , 5 with m a, 6 with Ⅲb and 5 with IV. The rates of successful drainage, complications, mean survival time of patients and the average duration of biliary stent patency were compared between the two groups. Results Successful rate of cannulation was both 100% in the two groups. Successful rate of drainage and complications of double stent group were 96.4% （27/28） and 17.9% （5/28）, and these two variables of single stent group were 87.0% （20/23） and 13.0% （ 3/23 ）, which were not significantly different （ P 〉 0.05 ）. 23 patients （82. 1% ） in double stent and 19 （82. 6% ） in single stent group were followed up. The average duration of stent patency and mean survival time of double stent group were （129 ± 48.5） d and （187 ± 94. 5） d, which were superior to those of the single stent group, i.e. （ 102 ± 37. 8） d and （ 103 ± 98.5 ） d. ConclusionDouble stenting is an effective therapy for malignant hilar obstruction of Bismuth I and above. It is superior to single stent method in the mean duration of patency and mean survival time. Key words: Bile duct obstruction; Neoplasms; Double stents drainage

Relationship between CacyBP/SIP expression and prognosis in astrocytoma

The aim of this study was to investigate the expression of calcyclin-binding protein (also known as Siah-1-interacting protein [CacyBP/SIP]) in astrocytoma and to determine its prognostic value in overall survival of patients with glioblastoma multiforme (GBM). Tissue specimens were obtained from 77 Chinese patients who had undergone surgery for astrocytoma. The expression of CacyBP/SIP was examined by immunohistochemistry. The relationship between CacyBP/SIP and proliferating cell nuclear antigen index (PCNA) expression was investigated, and the prognostic value of CacyBP/SIP expression in patients with astrocytomas was analyzed. Of 77 tumors, 49 (63.6%) were negative for CacyBP/SIP expression. Loss of CacyBP/SIP expression was significantly associated with a high histological grade and with poor survival in univariate and multivariate analyses. Cox multivariable analysis showed that loss of CacyBP/SIP expression correlated with poor prognosis in patients with astrocytomas and was an independent prognostic factor ( p < 0.05). The mean survival time of patients with tumors that had lost expression of CacyBP/SIP was 25.58 months (95% confidence interval [CI], 15.36–25.81 months), compared to a mean survival time of 36.37 months (95% CI, 27.90–44.84 months) for patients with CacyBP/SIP-expressing tumors. CacyBP/SIP expression was also negatively correlated with PCNA expression in astrocytoma tissue ( p < 0.05). Our findings suggest that CacyBP/SIP may have an important role as a negative regulator of astrocytoma development and progression, and that CacyBP/SIP might be a useful molecular marker for predicting the prognosis of astrocytoma.

Gamma knife surgery for non-small cell lung cancer patients with brain metastasis: A community cancer center experience.

e18054 Background: For patients with non-small cell lung cancer (NSCLC) and brain metastasis, the options available for treatment depend on several different factors. For those with brain metastasis who are qualifying candidates, gamma knife surgery (GKS) is an alternative to invasive neurosurgery. At Archbold Lewis Hall Singletary Oncology Center in Thomasville, Georgia, GKS can be provided as an option for treating NSCLC with brain metastasis. Our study performed in a small, community setting has shown results comparable to those found in patients treated in larger university settings. Methods: A retrospective review of 92 patients who had undergone GKS to treat a total of 276 NSCLC metastases was performed. Clinical data encompassing a 7-year treatment interval were collected. The histology of primary NSCLC was classified as adenocarcinoma (n=50), squamous (n=19), or undefined (n=23). Fifty-two patients had no active extra cranial disease at time of treatment with GKS and 24 patients received whole brain radiation therapy (WBRT) prior to GKS. A number of patients received concomitant regimen to primary site with radiation alone (n=10), chemo alone (n=9), radiation and chemo (n=30), surgery (n=31), none (n=9) and unknown (n=3). There were 48 men and 44 women, which were 75% Caucasian, 24% African American, and 1% Hispanic. The average patient age was 64.8. The average Karnofsky Perfomance Scale was 70.3. Results: The overall mean patient survival time was 9.9 months, ranging from 10 days to 78.7 months, from the date of first treatment of GKS. The mean survival time was 8.9 months for those diagnosed with adenocarcinoma, 10.8 months for those diagnosed with squamous cell carcinoma, and 11.6 months for those with undefined pathology. Mean survival time of patients without active extra cranial disease was 10.5 months. The patients that received WBRT prior to GKS averaged a survival of 16.7 months. African American patients had an average survival time of 7.8 months compared to 10.7 months for Caucasian patients. Conclusions: Gamma knife surgery for NSCLC with brain metastasis can serve as a treatment option in a community setting and produce results comparable to those seen in large university settings.

Abstract LB-96: Extrinsic and intrinsic force and GBM aggression

Abstract Despite concerted effort the mean survival time for patients with aggressive GBM remains unchanged with a mean of 14 months. Indeed, high grade GBMs are notoriously resistant to therapy and typically disseminate throughout the brain tissue, severely compromising patient treatment. In this respect, the most lethal GBMs arise within the SVZ region of the brain which is rich in stem cells. This has lead to speculation that GBM aggression is related to their stem-like origin. Consistently, using AFM indentation we determined that analogous to neural stem cells (NSCs), high grade GBMs are very soft and express high levels of the Notch regulated gene HES-1. We also found that high grade GBMs and NSCs both express elevated levels of the stemness-promoting repressor NCoR2. We further determined that NCoR2 expression correlates with poor GBM patient prognosis, which is an observation that accords with our recent finding that NCoR2 enhances breast tumor survival in response to radiation, chemotherapy and immune activators in vitro and in vivo. These findings are consistent with a stem-like origin for GBMs and identify NCoR2 as a putative unique survival mechanism that could explain the treatment resistance of this disease. Interestingly, AFM measurements of freshly excised murine brain tumor slices showed that GBMs arising within the SVZ region are also quite stiff. Preliminary findings also showed that isolated high grade GBM cells but not low grade oligodendroglioma cells have a greatly enhanced mechano-responsiveness e.g. they spread more on soft gels and possess a vastly altered glycocalyx; traits that predict elevated contractility and integrin signaling. Given MRI data indicating very aggressive GBMs in the SVZ region are highly vascularized and experience elevated compression the findings support the idea that tumors that arise within this highly mechanically-challenged SVZ microenvironment have a unique mechano-behavior that could facilitate their growth, survival and dissemination. Indeed, the high compliance, contractility and mechanical resistance of GBMs would facilitate their growth, survival and expansion within compressed brain tissue and would foster their ability to navigate and disseminate into the dense GBM-associated ECM. Because reducing tumor force can revert the malignant phenotype of cancerous tissue and will reduce tumor cell invasion, growth, and survival and inhibit tumor progression and decrease tumor incidence we predict that the altered force microenvironment and intrinsic mechanobehavior of GBMs contribute to their aggression. Consequently, studies are now underway to clarify the interplay between cell and tissue force and GBM behavior and to determine the relevance of NCoR2 to GBM treatment resistance. (Supp by: NCI grants U54CA143836–01 and NIH/NCI R01 CA138818–01A1 to V.M.W. and a National Science Foundation (GRFP) Fellowship to Y.A.M.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-96. doi:10.1158/1538-7445.AM2011-LB-96

Evaluation of REG4 for early diagnosis and prognosis of gastric cancer

We explored the correlation between the development of gastric cancer and the concentration of REG4 and hence the suitability of REG4 as an indicator of the prognosis of patients with GC. Real-time polymerase chain reaction was conducted to detect REG4 messenger RNA expression. The amount of the REG4 protein was measured by immunohistochemistry staining of tissue and enzyme-linked immunosorbent assay of serum. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 concentrations were measured using a commercial automated immunoassay. Real-time polymerase chain reaction results confirmed that REG4 was significantly up-regulated in gastric cancer compared with paired normal mucosa (P < .001). Immunohistochemistry staining revealed that high expression of REG4 correlated with diffuse type, poor differentiation, lymph node metastasis, distant metastasis, and TNM stage III or IV. The mean survival time for patients in the REG4-positive group was significantly less than that in the REG4-negative group (P = .013). The percentage of serum samples that were REG4 positive was 44.0%, which was higher than that for serum carcinoembryonic antigen (P = .039) or carbohydrate antigen 19-9 (P = .012) in TNM stage I and was significantly higher (P = .031) than that in TNM stage II. Thus, REG4 may be not only a prognostic indicator but also a better serum marker than carcinoembryonic antigen and carbohydrate antigen 19-9 for early diagnosis of gastric cancer.

The role of sentinel lymph node biopsy in patients with thick melanoma. A single centre experience

AimsTo evaluate the role, if any, of sentinel lymph node mapping (SLNM) with biopsy (SLNB) in patients with thick cutaneous melanoma. MethodsConsecutive patients with thick (Breslow ≥4 mm) cutaneous melanoma, undergoing SLNB were identified from a departmental database comprising 550 patients in total from 2000 to 2010. Factors examined included demographic data, histological subtype, site and depth of lesion, percentage of positive SLNs, regional recurrence in the setting of a negative SLNB result (false-negative rate), complications, further lymphadenectomy, and follow-up (disease free and overall survival), where available. ResultsSixty-four eligible patients (37 men, 27 women) underwent primary excision and SLNM. Median patient age was 59 years (range 8–82 years). Mean Breslow depth was 7 mm (range 4–19 mm). Thirty melanomas were located on the limbs, 19 on the head and neck and 15 on the trunk. Twenty-three (35%) were ulcerated. Of the 57 patients who had a sentinel node identified, 18 (31%) had metastatic melanoma identified. The mean survival time for patients with a negative SLN was 79 months versus 18 months for those with a positive node. Patients with a negative SLN have a 5 year disease free survival of 79% versus 11% (p < 0.001) and an overall 5 year survival rate of 85% versus 32% when compared to node positive patients. ConclusionsThe status of the SLN is predictive of disease recurrence and overall survival in patients with a thick primary cutaneous melanoma. This modality should be employed, where applicable, in this cohort of patients.

High mortality in orthotopic liver transplant recipients who require hemodialysis

Acute renal failure is a significant risk factor for death in patients with liver failure. The goal of this study was to analyze the impact of peri-transplant dialysis on the long-term mortality of liver transplant recipients. We performed a single-center, retrospective cohort study of 743 adult liver transplants; patients who received first liver transplants were divided into four groups: those who received more than one dialysis treatment (hemodialysis [HD], continuous veno-venous hemodialysis [CVVH]) pre-orthotopic liver transplantation (OLT), post OLT, pre- and post OLT, and those not dialyzed. There was no statistically significant difference in the mean survival time for patients who were not dialyzed or dialyzed only pre-OLT. Mean survival times were markedly reduced in patients dialyzed post OLT or both pre- and post OLT compared with those never dialyzed. Mortality risk in a Cox proportional hazards model correlated with hemodialysis post OLT, intra-operative vasopressin or neosynephrine, donor age >50 yr, Cr >1.5 mg/dL at transplant, and need for subsequent retransplant. Risk of post-OLT dialysis was correlated with pre-OLT dialysis, intra-operative levophed, pre-OLT diabetes, African American race, pre-OLT Cr >1.5, and male gender. We conclude that renal failure requiring hemodialysis post liver transplant, irrespective of pre-transplant dialysis status, is a profound risk factor for death in liver transplant recipients.

Are endoscopic or percutaneous biliary drainage effective forobstructive jaundice caused by hepatocellular carcinoma?

The prognosis of patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) has been reported to be poor. The aims of this study were to determine whether effective biliary drainage in patients with obstructive jaundice caused by HCC can affect clinical outcome and to identify those factors that affect effective biliary drainage and clinical outcome. The clinical records of 68 patients with obstructive jaundice caused by HCC who underwent endoscopic or percutaneous transhepatic biliary drainage from 1 January 2004 to 31 December 2008 were analyzed. Effective biliary drainage was defined as a decrease in total bilirubin level of more than 30% of the preprocedural value within 4 weeks. (i) Effective biliary drainage was achieved in 51.5% of the patients who underwent a biliary drainage procedure. The independent risk factors for ineffective biliary drainage were total bilirubin more than 13 mg/dl and Child-Turcotte-Pugh class C. (ii) Patients with effective biliary drainage showed a significant improvement of Child-Turcotte-Pugh class and received additional treatment for HCC. (iii) The mean survival times of patients who received effective or ineffective biliary drainage were 247 and 44 days, respectively. (iv) The independent risk factors of mortality were an age of more than 63 years, ineffective biliary drainage, and no following treatment for HCC. When effective biliary drainage was achieved after an appropriate biliary drainage procedure in patients with obstructive jaundice caused by HCC, survival improved.