Influence Patient Survival Research Articles

Moderate level of HER2 expression and its prognostic significance in breast cancer with intermediate grade.

Overexpression of human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive marker of response to anti-HER2 therapy in breast cancer. Our goal was to analyze the prognostic significance of moderate expression of HER2 in breast cancer with intermediate differentiation grade. We performed a multicenter retrospective register study of 8494 patients with primary non-metastatic breast cancer admitted between 2000 and 2011 to eight Clinics in Saxony-Anhalt, federal state of Germany. Patients were divided into three groups according to their HER2 score: 4073 were classified as HER2 negative (HER2 0 and 1+), 822 HER2 moderate (HER2 2+/HER2), and 1238 HER2 positive (HER2 3+ or HER2 2+/HER2+). HER2-positive cases were excluded from analysis. Tumors with moderate HER2 (HER2 2+) expression demonstrated an aggressive behavior and worse patient survival compared with HER2 0 and 1+ status. HER2 2+ status was associated with shorter median overall survival (OS) (P < 0.0001) in breast cancer patients with an intermediate grade of differentiation. Comparing low-grade and high-grade tumors, HER2 moderate expression did not significantly influence patient survival. In multivariate analysis after adjustment for other prognostic factors HER2 2+ status remained an unfavorable prognostic factor for OS (HR 1.224, 95 % CI 1.059-1.415, P = 0.006) in breast cancer patients with an intermediate grade of differentiation. HER2 2+ status is an unfavorable prognostic factor regarding the OS of breast cancer patients with intermediate grade of differentiation and could be used to identify patients, who may benefit from adjuvant therapy.

The Efficacy of Intraluminal Brachytherapy as Palliative Therapy of Hilar Cholangiocarcinoma

Background/Aims: The aim of this study is to assess the therapeutic benefits of a combination of external beam radiation therapy (EBRT) and intraluminal brachytherapy (ILBT) in hilar cholangiocarcinoma as palliative therapy. Methods: A total of 21 patients with hilar cholangiocarcinoma were included. Only 12 patients were treated with EBRT (group 1), and only nine patients were treated with EBRT and ILBT (group 2). The survival data and stent patency period were measured in both groups and the results were compared. Results: No statistically significant difference in patient survival was observed between the two groups. The median survival period of group 1 was 353 days and that of group 2 was 224 days. Also, stent patency did not differ significantly between groups. The period for group 1 was 250 days, and that of group 2 was 133 days. In addition, there were no other factors influencing patient survival and stent patency period. However, patient survival tended to increase with increase in the amount of irradiation dose (Spearman’s correlation coefficient=0.65, p =0.065). Conclusions: EBRT with ILBT did not have a benefit when compared with the treatment effect of EBRT alone as palliative therapy for hilar cholangiocarcinoma. Korean J Pancreatobiliary 2015;20(2):71-77

HIF-2α attenuates lymphangiogenesis by up-regulating IGFBP1 in hepatocellular carcinoma.

Tumour-associated lymphangiogenesis was identified as an important clinical determinant for the prognosis of hepatocellular carcinoma (HCC) and significantly influences patient survival. However, in this context, little is known about regulation of lymphangiogenesis by hypoxia-inducible factors (HIF). In HCC, mainly HIF-1α was positively correlated with lymphatic invasion and metastasis, whereas a defined role of HIF-2α is missing. We created a stable knockdown (k/d) of HIF-1α and HIF-2α in HepG2 cells and generated co-cultures of HepG2 spheroids with embryonic bodies. This constitutes an in vitro tumour model mimicking the cancer microenvironment and allows addressing the role of distinct HIF isoforms in regulating HCC lymphangiogenesis. In co-cultures with a HIF-2α k/d, lymphangiogenesis was significantly increased, whereas the k/d of HIF-1α showed no effect. The HIF-2α-dependent lymphangiogenic phenotype was confirmed in vivo using matrigel plug assays with supernatants of HIF-2α k/d HepG2 cells. We identified and verified insulin-like growth factor binding protein 1 (IGFBP1) as a HIF-2α target gene. The potential of HepG2 cells to induce lymphangiogenesis in two independent functional assays was significantly enhanced either by a k/d of HIF-2α or by silencing IGFBP1. Moreover, we confirmed IGF as a potent pro-lymphatic growth factor with IGFBP1 being its negative modulator. We propose that HIF-2α acts as an important negative regulator of hepatic lymphangiogenesis in vitro and in vivo by inducing IGFBP1 and thus, interfering with IGF signalling. Therefore, HIF-2α may constitute a critical target in HCC therapy.

Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats.

Approximately 42% of patients with sepsis undergo acute kidney injury (AKI), which evidently influences patient survival. However, effective therapy strategies are lacking, thus, the present study investigated the protective effects of dexmedetomidine (DEX), a highly selective α-2 adrenoceptor agonist, in rat sepsis models. Rat sepsis models were generated through lipopolysaccharide injection (LPS; 5 mg/kg) in the tail vein. Rats were pretreated with DEX (10 µg/kg) 10 min before LPS injection to observe its protective effects. Of note, a unique α-2-adrenergic receptor antagonist, yohimbine (YOH; 1 mg/kg, intraperitoneally), was also used to antagonize the protective effects of DEX 30 min before DEX exposure. Thirty-two male Sprague Dawley rats were randomly divided into the Sham, LPS, DEX + LPS and YOH + DEX + LPS groups (n=8/group). All the rats were sacrificed 4 h later to observe the pathological changes of renal tissue, including plasma creatinine (Cr), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1) and high mobility group protein 1 (HMGB-1) expression. Interleukin 6 (IL-6), IL-18 and tumor necrosis factor α (TNF-α) were all determined to examine the mechanisms of LPS-induced AKI relative to inflammatory reaction. The results indicated that AKI induced by LPS was serious. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18 and TNF-α were all evidently increased in varying degrees. KIM-1 and HMGB-1 expression was upregulated in the LPS group (P<0.05 vs. Sham group). However, when rats were pretreated with DEX, AKI induced by LPS was decreased significantly. Renal pathological injury, plasma Cr, BUN, IL-6, IL-18, TNF-α, and KIM-1 and HMGB-1 expression were all reduced (P<0.05 vs. LPS group). In addition, exposure of the α-2-adrenergic receptor antagonist, YOH, eliminated this reduction. In conclusion, DEX protected against sepsis-induced AKI through depressing the inflammatory reaction, mechanisms of which may be associated with α-2 receptors inhibition.

Cyclic nucleotide phosphodiesterase-1C (PDE1C) drives cell proliferation, migration and invasion in glioblastoma multiforme cells in vitro.

Cyclic nucleotides (cAMP & cGMP) are critical intracellular second messengers involved in the transduction of a diverse array of stimuli and their catabolism is mediated by phosphodiesterases (PDEs). We previously detected focal genomic amplification of PDE1C in >90 glioblastoma multiforme (GBM) cells suggesting a potential as a novel therapeutic target in these cells. In this report, we show that genomic gain of PDE1C was associated with increased expression in low passage GBM-derived cell cultures. We demonstrate that PDE1C is essential in driving cell proliferation, migration and invasion in GBM cultures since silencing of this gene significantly mitigates these functions. We also define the mechanistic basis of this functional effect through whole genome expression analysis by identifying down-stream gene effectors of PDE1C which are involved in cell cycle and cell adhesion regulation. In addition, we also demonstrate that Vinpocetine, a general PDE1 inhibitor, can also attenuate proliferation with no effect on invasion/migration. Up-regulation of at least one of this gene set (IL8, CXCL2, FOSB, NFE2L3, SUB1, SORBS2, WNT5A, and MMP1) in TCGA GBM cohorts is associated with worse outcome and PDE1C silencing down-regulated their expression, thus also indicating potential to influence patient survival. Therefore we conclude that proliferation, migration, and invasion of GBM cells could also be regulated downstream of PDE1C.

The faster the better: anastomosis time influences patient survival after deceased donor kidney transplantation.

Despite a continuously growing knowledge of the impact of factors on kidney graft function, such as donor age, body mass index, and cold ischemia time, few data are available regarding anastomosis time (AT) and its impact on long-term results. We investigated whether surgical AT correlates with patient and graft survival after kidney transplantation performing a retrospective analysis of 1245 consecutive deceased donor kidney transplantations between 01/2000 and 12/2010 at Innsbruck Medical University. Kaplan-Meier and log-rank analyses were carried out for 1- and 5-year patient and graft survival. AT was defined as time from anastomosis start until reperfusion. Median AT was 30 min. Five-year survival of allografts with an AT >30 min was 76.6% compared with 80.6% in the group with AT <30 min (P = 0.027). Patient survival in the group with higher AT similarly was inferior with 85.7% after 5 years compared with 89.6% (P < 0.0001) [Correction added on February 18, 2015, after first online publication: the percentage value for patient survival was previously incorrect and have now been changed to 89.6%]. Cox regression analysis revealed AT as an independent significant factor for patient survival (HR 1.021 per minute; 95% CI 1.006-1.037; P = 0.006). As longer AT closely correlates with inferior long-term patient survival, it has to be considered as a major risk factor for inferior long-term results after deceased donor kidney transplantation.

Second-line treatment of metastatic gastric cancer: Current options and future directions.

Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase III trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.

Concurrent chemoradiotherapy with vinorelbine plus split-dose cisplatin may be an option in inoperable stage III non-small cell lung cancer: a single-center experience.

BackgroundConcurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) in patients with inoperable stage III NSCLC followed in our oncology clinic.Material/MethodsMedical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m2) and vinorelbine (20 mg/m2) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system.ResultsOur study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39–75) and 87 (89.7%) of the patients were men. ECOG performance score was 0–1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3–4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity.ConclusionsThe results of this study suggest that split-dose cisplatin may offer fewer grade III–IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.

Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome.

Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]). Area under the curve of the ROC curve (0.77 [0.74–0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001). Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.

The Effect of Differentiation Grade of Cutaneous Squamous Cell Carcinoma on Excision Margins, Local Recurrence, Metastasis, and Patient Survival

The incidence of cutaneous squamous cell carcinoma (SCC) is increasing worldwide. Despite a growing body of literature on prognostic factors, it remains unclear how tumor differentiation grade influences patient survival. The aim of this study was to investigate a possible correlation between cutaneous SCC differentiation, local recurrence, metastasis, and patient survival. All consecutive patients treated for cutaneous SCC between 2001 and 2008 were retrospectively analyzed. Univariate survival analysis was used to assess the association of different tumor characteristics with survival. One hundred thirty-one patients with 155 SCCs were included (median follow-up, 81 months; range, 27-125 months). Although no significant correlation between tumor differentiation grade and local recurrence could be found, it was an independent prognostic factor for metastatic disease and overall survival (OS). Metastasis-free survival at 5 years was significantly higher in well-differentiated tumors (70%) compared to moderately (51%) and poorly differentiated SCCs (26%; P = 0.012); identical percentages were found for OS (P = 0.005). Furthermore, patients with incomplete excision of the first tumor showed an increased relative risk of dying of SCC of 4.0 (95% confidence interval, 2.4-6.6; P < 0.001) compared to excision with clear margins. Studies that investigated the relationship between SCC differentiation grade and patient survival are scarce and inconsistent. The present study indicates tumor differentiation grade is an independent prognostic factor for OS. This finding suggests poor differentiation of cutaneous SCC alone is sufficient to upstage the primary tumor in the TNM classification system.

Predictive and Prognostic Significance of Immunohistochemical Markers and Blood Absolute Lymphocyte Count in Diffuse Large B-Cell Lymphoma in Rituximab Era: A Polish Lymphoma Research Group (PLRG) Multicenter Retrospective Analysis

This report is a retrospective analysis of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were treated with R-CHOP-21. The aim of the study was to determine the impact of peripheral blood absolute lymphocyte count (ALC), Ki67 proliferation index and immunohistochemical expression of Bcl-2 and Bcl-6 at diagnosis on complete response rate and survival.The study group consisted of 161 patients with stage II-IV who were treated with six cycles of R-CHOP-21 between January 2004 and December 2013. With International Prognostic Index (IPI), 29% patients were low, 29% low-intermediate, 25% high-intermediate and 17% high risk. Bcl-2 and Bcl-6 expression was detected with immunohistochemical staining on paraffin sections in 83% and 77% of patients, respectively. Bcl-2 expression with high Ki67 proliferation index, greater than 80%, was found in 15% of patients. BcL-6 expression with Ki67 index of 80% or lower was detected in 52% of patients. Median ALC at diagnosis was 1.4 G/L (0.1-4.2). ALC below 1.0 G/L was revealed in 27% patients.Results: The complete response rate to R-CHOP was 69%. In univariate logistic regression for complete response to immunochemotherapy, the variables that were correlated with lower response rate were IPI > 2 (p=0.016) and ALC < 1.0 G/L (p=0.014). In multivariate logistic regression, ALC < 1.0 G/L remained the only independent variable associated with failure to achieve complete response (OR 2.6; 95%CI 1.2-5.9; p=0.03). After the median follow-up time of 37 months (6-109), the 5-year progression free and overall survival (OS) estimated with Kaplan-Meier method were 67% (95% CI 56-76) and 66% (95% CI 55-75), respectively. In univariate analysis IPI (log-rank test, p=0.001), ALC (log-rank test, p=0.009) (fig.1), Bcl-2 expression with high Ki67 index (log-rank test, p=0.015) (fig.2) and Bcl-6 expression with low Ki67 index (log-rank test, p=0.05) were statistically significant for OS. In the multivariate analysis with Cox model, ALC at diagnosis (HR 2.9; 95%CI 1.1-7.3; p=0.024) and Bcl-2 expression with high Ki67 index (HR 2.8; 95%CI 1.1-7.5; p=0.039) remained significant for OS. IPI higher than 2 tended to impact negatively OS (HR 2.4; 95%CI 0.9-6.3; p=0.067).In conclusion, our results indicate that low ALC at diagnosis is independent predictor of poor response to R-CHOP for patients with DLBCL. In addition, low ALC and Bcl-2 expression with high Ki67 index adversely influence patient survival in the rituximab era. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Acute myeloid leukemia: survival analysis of patients at a university hospital of Paraná.

ObjectiveThe aim of this study was to analyze the prognostic factors correlated with survival of patients with acute myeloid leukemia at the Hospital de Clínicas, Universidade Federal do Paraná between 2003 and 2009, as well as to investigate the clinical and epidemiological profile.MethodsThe overall survival and disease-free survival were statistically evaluated using the Kaplan–Meier method, the log-rank test and multivariate evaluation by Cox regression analysis.ResultsThe study population was predominantly younger than 60 years old (81,6%), had intermediate cytogenetic risk (40.8%), in first complete remission after induction chemotherapy (46.9%), with a white blood count at diagnosis of less than 30 × 109/L (57.1%) and de novo acute myeloid leukemia (62.2%). Survival curves showed that better prognosis was related to age below 60 years (median:12,4 months; p-value = 0,2227; Odds Ratio = 0,6676), good prognostic cytogenetic markers (median: 97.7 months; p-value = 0.0037; Odds Ratio = 0.4239) and white blood cell count at diagnosis of less than 30 × 109/L (median survival: 23.6 months; p-value = 0.0001; Odds Ratio = 0.3651). Regarding the French-American-British subgroups, the median overall survival was 23.5 months for M0, M1 and M2, 97.7 months for M3 and 7.4 months for M4, M5, M6, and M7 (p-value = 0.0288).ConclusionPrognostic factors strongly influenced patient survival, as well as guided treatment. Moreover, these factors were consistent with the available literature adjusted for the population in question.

Local recurrence and survival in acral lentiginous melanoma comparing 3D histology and conventional histology

Background Surgical treatment of acral lentiginous melanomas with wide excisional margins as recommended often requires amputation of distal extremities. The current study analyzes whether smaller excisions in combination with a complete histological evaluation of the excisional margins (3D histology) have a negative impact on the prognosis. Patients and methods 304 patients were retrospectively evaluated. 192 patients with reduced excisional margins followed by 3D histology (group A) were compared with 112 patients treated with conventional wide margins (group B). The outcome of both groups was compared. Results The median tumor thickness was higher in group A (p = 0.022) and ulcerations occured more frequently (p = 0.017). The median excisional margin was 8 mm in group A and 20 mm in group B (p < 0.0001). 10.9 % (4.2 % invasive) of group A und 8.9 % (4.5 % invasive) of group B (p = 0.577) developed a local recurrence in a median of 40 months. The melanoma specific 10-year survival was 66.8 % in group A und 63.4 % in group B (p = 0.531). There was no difference in survival of patients with or without local recurrence (p = 0.643). Conclusions Excision with small margins followed by 3D histology is not inferior to conventional surgery with wide margins in terms of the rate of local and has no negative impact on prognosis or the further course of the disease. Local recurrences are rare and do not influence patient survival.

The Faster the Better: Anastomosis Time Influences Patient Survival Significantly After Deceased Donor Kidney Transplantation.

The Faster the Better: Anastomosis Time Influences Patient Survival Significantly After Deceased Donor Kidney Transplantation.

Induction of p53-mediated transcription and apoptosis by exportin-1 (XPO1) inhibition in mantle cell lymphoma.

The nuclear transporter exportin-1 (XPO1) is highly expressed in mantle cell lymphoma (MCL) cells, and is believed to be associated with the pathogenesis of this disease. XPO1-selective inhibitors of nuclear export (SINE) compounds have been shown to induce apoptosis in MCL cells. Given that p53 is a cargo protein of XPO1, we sought to determine the significance of p53 activation through XPO1 inhibition in SINE-induced apoptosis of MCL cells. We investigated the prognostic impact of XPO1 expression in MCL cells using Oncomine analysis. The significance of p53 mutational/functional status on sensitivity to XPO1 inhibition in cell models and primary MCL samples, and the functional role of p53-mediated apoptosis signaling, were also examined. Increased XPO1 expression was associated with poor prognosis in MCL patients. The XPO1 inhibitor KPT-185 induced apoptosis in MCL cells through p53-dependent and -independent mechanisms, and p53 status was a critical determinant of its apoptosis induction. The KPT-185-induced, p53-mediated apoptosis in the MCL cells occurred in a transcription-dependent manner. Exportin-1 appears to influence patient survival in MCL, and the SINE XPO1 antagonist KPT-185 effectively activates p53-mediated transcription and apoptosis, which would provide a novel strategy for the therapy of MCL.

Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases.

To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival. A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases in 2009 and 2010 at a tertiary referral center. Variables related to postoperative survival were all included in the same multivariable logistic regression analysis with either 3- or 12-month survival as the dependent variable. The independent variables were: transfusion of allogenic red blood cells, age at surgery, gender, preoperative hemoglobin, revised Tokuhashi score and no. of instrumented levels. Perioperative allogenic blood transfusion of 1-2 units was associated with increased 12-month survival [p=0.049, odds ratio 2.619 (confidence interval 1.004-6.831)], but not with 3-month survival. Larger transfusion volumes did not significantly influence survival. The results of the present study support that perioperative blood transfusion of <5 units does not decrease survival in patients operated for spinal metastases. Transfusion of 1-2 units seems to be associated with increased 12-month survival. Future studies should assess if a liberal transfusion regime can be applied to this group of patients; thereby, prioritizing early postoperative mobilization.

Impact of farnesylation inhibitors on survival in Hutchinson-Gilford progeria syndrome.

Hutchinson-Gilford progeria syndrome is an ultrarare segmental premature aging disease resulting in early death from heart attack or stroke. There is no approved treatment, but starting in 2007, several recent single-arm clinical trials administered inhibitors of protein farnesylation aimed at reducing toxicity of the disease-producing protein progerin. No study assessed whether treatments influence patient survival. The key elements necessary for this analysis are a robust natural history of survival and comparison with a sufficiently large patient population that has been treated for a sufficient time period with disease-targeting medications. We generated Kaplan-Meier survival analyses for the largest untreated Hutchinson-Gilford progeria syndrome cohort to date. Mean survival was 14.6 years. Comparing survival for treated versus age- and sex-matched untreated cohorts, hazard ratio was 0.13 (95% confidence interval, 0.04-0.37; P<0.001) with median follow-up of 5.3 years from time of treatment initiation. There were 21 of 43 deaths in untreated versus 5 of 43 deaths among treated subjects. Treatment increased mean survival by 1.6 years. This study provides a robust untreated disease survival profile that can be used for comparisons now and in the future to assess changes in survival with treatments for Hutchinson-Gilford progeria syndrome. The current comparisons estimating increased survival with protein farnesylation inhibitors provide the first evidence of treatments influencing survival for this fatal disease. http://www.clinicaltrials.gov. Unique Indentifiers: NCT00425607, NCT00879034, and NCT00916747.

Which Cannulation Technique for Which Patient

Cannulation of arteriovenous (AV) access is a crucial part of vascular access management in hemodialysis patients. It can significantly affect survival of the AV access, and consequently, it probably influences patient survival. The best type of cannulation technique, rotating site versus constant site (or buttonhole), is currently debated, but the increase in infectious complications observed with the buttonhole technique suggests a prudent use of this technique, restricting it to specific patients. Even in cases with a specific indication, the balance between advantages of the constant site needling and the potentially severe consequences of access related systemic infection should be considered. Educational efforts in improving cannulation skills of dialysis staff are important for improving outcomes, as the proper use of the rotating site technique might still be the best approach to cannulation.

Prognosis of esophageal squamous cell carcinoma patients with preoperative radiotherapy: Comparison of different cancer staging systems.

The 7th edition American Joint Committee on Cancer tumor-node-metastasis (AJCC TNM) staging system was published in 2010. Here we evaluate its predictive ability and compare the 6th and 7th editions of the AJCC TNM staging systems in esophageal squamous cell cancer (ESCC) with preoperative radiotherapy. A total of 296 esophageal squamous cell carcinoma patients receiving preoperative radiotherapy between 1980 and 2007 were included. Patients were staged using the 6th and 7th edition staging systems. Survival analyses were performed using Cox regression models. The homogeneity, discriminatory ability, and monotonicity of gradients of the two staging systems were compared using linear trend χ(2), likelihood ratio statistics, and Akaike information criterion calculation. The overall five-year survival rate for the entire cohort was 27.1%. Female gender, length, "T," and "N," classifications according to the 7th edition staging system were the prognostic factors in univariate analyses. However, tumor histological grade and cancer location did not significantly influence patient survival. The 7th edition staging system has the highest linear trend χ(2)and likelihood ratio χ(2)scores. Compared to the 6th edition, the 7th edition staging system also has a smaller Akaike information criterion value, which represents the optimum prognostic stratification. The strength of the 7th edition AJCC TNM staging system lies in the new descriptors for "T" and "N" classifications. However, we did not find cancer location to be a significant prognostic factor in our cohort. Overall, the 7th edition AJCC TNM staging system performed better than the previous edition.

Treatment of medulloblastoma with oncolytic measles viruses expressing the angiogenesis inhibitors endostatin and angiostatin

BackgroundMedulloblastoma is the most common type of pediatric brain tumor. Although numerous factors influence patient survival rates, more than 30% of all cases will ultimately be refractory to conventional therapies. Current standards of care are also associated with significant morbidities, giving impetus for the development of new treatments. We have previously shown that oncolytic measles virotherapy is effective against medulloblastoma, leading to significant prolongation of survival and even cures in mouse xenograft models of localized and metastatic disease. Because medulloblastomas are known to be highly vascularized tumors, we reasoned that the addition of angiogenesis inhibitors could further enhance the efficacy of oncolytic measles virotherapy. Toward this end, we have engineered an oncolytic measles virus that express a fusion protein of endostatin and angiostatin, two endogenous and potent inhibitors of angiogenesis.MethodsOncolytic measles viruses encoding human and mouse variants of a secretable endostatin/angiostatin fusion protein were designed and rescued according to established protocols. These viruses, known as MV-hE:A and MV-mE:A respectively, were then evaluated for their anti-angiogenic potential and efficacy against medulloblastoma cell lines and orthotopic mouse models of localized disease.ResultsMedulloblastoma cells infected by MV-E:A readily secrete endostatin and angiostatin prior to lysis. The inclusion of the endostatin/angiostatin gene did not negatively impact the measles virus’ cytotoxicity against medulloblastoma cells or alter its growth kinetics. Conditioned media obtained from these infected cells was capable of inhibiting multiple angiogenic factors in vitro, significantly reducing endothelial cell tube formation, viability and migration compared to conditioned media derived from cells infected by a control measles virus. Mice that were given a single intratumoral injection of MV-E:A likewise showed reduced numbers of tumor-associated blood vessels and a trend for increased survival compared to mice treated with the control virus.ConclusionsThese data suggest that oncolytic measles viruses encoding anti-angiogenic proteins may have therapeutic benefit against medulloblastoma and support ongoing efforts to target angiogenesis in medulloblastoma.