Anemia is associated with abdominal aortic aneurysm (AAA) size and decreased long-term survival after endovascular AAA repair

OBJECTIVE: Anemia is a common comorbid condition in various inflammatory states and an established predictor of mortality in patients with chronic heart failure, ischemic heart disease, and end-stage renal disease. The present study of patients with abdominal aortic aneurysm (AAA) undergoing endovascular repair (EVAR) assessed the relationships between baseline hemoglobin concentration and AAA size, as well as anemia and long-term survival. METHODS: Between March 1994 and November 2006, 711 patients (65 women, mean age 75.8 +/- 7.8 years) underwent elective EVAR. Anemia was defined as a hemoglobin level <13 g/dL in men and <12 g/dL in women. Post-EVAR mean follow-up was 48.3 +/- 32.0 months. Association of hemoglobin level with AAA size was assessed with multiple linear regression. Mortality was determined with use of the internet-based Social Security Death Index and the electronic hospital record. Kaplan-Meier survival curves of anemic and nonanemic patient groups were compared by the log-rank method. Multivariable logistic regression models were used to determine the influence of anemia on vital status after EVAR. RESULTS: A total of 218/711 (30.7%) of AAA patients undergoing EVAR had anemia at baseline. After adjustment for various risk factors, hemoglobin level was inversely related to maximum AAA diameter (beta: - .144, 95%-CI: -1.482 - .322, P = .002). Post-EVAR survival was 65.5% at 5 years and 44.4% at 10 years. In long-term follow-up, survival was significantly lower in patients with anemia as compared to patients without anemia (P < .0001 by log-rank). Baseline hemoglobin levels were independently related to long-term mortality in multivariable Cox regression analysis adjusted for various risk factors (adjusted HR: 0.866, 95% CI: .783 to .958, P = .005). Within this model, statin use (adjusted HR: .517, 95% CI: .308 to .868, P = .013) was independently related to long-term survival, whereas baseline AAA diameter (adjusted HR: 1.022, 95% CI: 1.009 to 1.036, P = .001) was an independently associated with increased mortality. CONCLUSIONS: Baseline hemoglobin concentration is independently associated with AAA size and reduced long-term survival following EVAR. Thus, the presence or absence of anemia offers a potential refinement of existing risk stratification instruments.

IDH/MGMT-driven molecular classification of low-grade glioma is a strong predictor for long-term survival

BACKGROUND Low-grade gliomas (LGGs) are rare brain neoplasms, with survival spanning up to a few decades. Thus, accurate evaluations on how biomarkers impact survival among patients with LGG require long-term studies on samples prospectively collected over a long period. METHODS The 210 adult LGGs collected in our databank were screened for IDH1 and IDH2 mutations (IDHmut), MGMT gene promoter methylation (MGMTmet), 1p/19q loss of heterozygosity (1p19qloh), and nuclear TP53 immunopositivity (TP53pos). Multivariate survival analyses with multiple imputation of missing data were performed using either histopathology or molecular markers. Both models were compared using Akaike's information criterion (AIC). The molecular model was reduced by stepwise model selection to filter out the most critical predictors. A third model was generated to assess for various marker combinations. RESULTS Molecular parameters were better survival predictors than histology (ΔAIC = 12.5, P< .001). Forty-five percent of studied patients died. MGMTmet was positively associated with IDHmut (P< .001). In the molecular model with marker combinations, IDHmut/MGMTmet combined status had a favorable impact on overall survival, compared with IDHwt (hazard ratio [HR] = 0.33, P< .01), and even more so the triple combination, IDHmut/MGMTmet/1p19qloh (HR = 0.18, P< .001). Furthermore, IDHmut/MGMTmet/TP53pos triple combination was a significant risk factor for malignant transformation (HR = 2.75, P< .05). CONCLUSION By integrating networks of activated molecular glioma pathways, the model based on genotype better predicts prognosis than histology and, therefore, provides a more reliable tool for standardizing future treatment strategies.

Prolonged inflammation following critical illness may impair long-term survival: a hypothesis with potential therapeutic implications

Despite successful intensive care a substantial portion of critically ill patients dies after discharge from the intensive care unit or hospital. Observational studies investigating long-term survival of critically ill patients reported that most deaths occur during the first months or year after discharge. Only limited data on the causes of impaired quality of life and post-intensive care unit deaths exist in the current literature. In this manuscript we hypothesize that the acute inflammatory response which characteristically accompanies critical illness is ensued by a prolonged imbalance or activation of the immune system. Such a chronic low-grade inflammatory response to critical illness may be sub-clinical and persist for a variable period of time after discharge from the intensive care unit and hospital. Chronic inflammation is a well-recognized risk factor for long-term morbidity and mortality, particularly from cardiovascular causes, and may thus partly contribute to the impaired quality of life as well as increased morbidity and mortality following intensive care unit and hospital discharge of critically ill patients. Assuming that critical illness is indeed followed by a prolonged inflammatory response, important implications for treatment would arise. An interesting and potentially beneficial therapy could be the administration of immune-modulating drugs during the time after intensive care unit or hospital discharge until chronic inflammation has subsided. Statins are well-investigated and effective drugs to attenuate chronic inflammation and could potentially also improve long-term outcome of critically ill patients after intensive care unit or hospital discharge. Future studies evaluating the course of inflammation during and after critical illness as well as its response to statin therapy are required.

Long term survival after trimodal therapy in malignant pleural mesothelioma

Trimodal therapy results in long term survival in a small fraction of patients with malignant pleural mesothelioma, particularly in patients having epithelial histology, R0-resection and no nodal involvement. This study analyses the outcome after trimodal therapy including extrapleural pneumonectomy.

Impact of age and comorbidities on long-term survival of patients with high-risk prostate cancer treated with radical prostatectomy: a multi-institutional competing-risks analysis

Survival after surgical treatment using competing-risk analysis has been previously examined in patients with prostate cancer (PCa). However, the combined effect of age and comorbidities has not been assessed in patients with high-risk PCa who might have heterogeneous rates of competing mortality despite the presence of aggressive disease.

Objective response to radiation therapy and long-term survival of patients with WHO grade II astrocytic gliomas with known LOH 1p/19q status

BACKGROUND: WHO grade II gliomas are often approached by radiation therapy (RT). However, little is known about tumor response and its potential impact on long-term survival. PATIENTS AND METHODS: Patients subjected to RT were selected from the own database of WHO grade II gliomas diagnosed between 1991 and 2000. The volumetric tumor response after RT was assessed based on magnetic resonance imaging and graded according to standard criteria as complete, partial (PR, >or= 50%), or minor (MR, 25% to <50%). RESULTS: There were 24 astrocytomas and three oligoastrocytomas. 21 patients (78%) were dead at follow-up (mean survival 74 months). None of the patients had chemotherapy. Objective response occurred in 14 patients (52%, five PR and nine MR) but was not associated with overall survival. The vast majority of the tumors had no loss of heterozygosity (LOH) 1p and/or 19q (86%). CONCLUSION: Approximately 50% of patients with astrocytic WHO grade II gliomas respond to RT despite the absence of LOH for 1p/19q. The potential predictive factors for response and the impact of response on overall survival remain unclear.

Clinical outcome and long-term survival in 118 consecutive patients with neuroendocrine tumours of the pancreas

BACKGROUND: The aim was to assess the clinical relevance of the World Health Organization and tumour node metastasis (TNM) classifications in patients with pancreatic neuroendocrine tumours (pNETs). METHODS: Prospectively collected data from 118 consecutive patients with a pNET receiving surgical intervention were analysed. RESULTS: Forty-one patients had well differentiated neuroendocrine tumours, 64 had well differentiated neuroendocrine carcinomas and 13 had poorly differentiated neuroendocrine carcinomas. Five-year survival rates were 95, 44 and 0 per cent respectively (P < 0.001). There was no difference in survival after R0 and R1/R2 resections in patients with neuroendocrine carcinomas (P = 0.905). In those with well differentiated neuroendocrine carcinomas, any resection and having a clinically non-functional tumour significantly increased survival (P = 0.003 and P = 0.037 respectively). The TNM stage was I in 37 patients, II in 15 patients, III in 32 patients and IV in 34 patients. There were significant differences in 5-year survival between stage I and II (88 and 85 per cent respectively) and stage III and IV (31 and 42 per cent respectively) (P = 0.010). CONCLUSION: Both classifications accurately reflect the clinical outcome of patients with pNET. The resection status may not be critical for long-term survival in patients with pNET.

Influence of deep sternal wound infection on long-term survival after cardiac surgery

BACKGROUND: This study aimed to investigate the influence of deep sternal wound infection on long-term survival following cardiac surgery. MATERIAL AND METHODS: In our institutional database we retrospectively evaluated medical records of 4732 adult patients who received open-heart surgery from January 1995 through December 2005. The predictive factors for DSWI were determined using logistic regression analysis. Then, each patient with deep sternal wound infection (DSWI) was matched with 2 controls without DSWI, according to the risk factors identified previously. After checking balance resulting from matching, short-term mortality was compared between groups using a paired test, and long-term survival was compared using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Overall, 4732 records were analyzed. The mean age of the investigated population was 69.3±12.8 years. DSWI occurred in 74 (1.56%) patients. Significant independent predictive factors for deep sternal infections were active smoking (OR 2.19, CI95 1.35-3.53, p=0.001), obesity (OR 1.96, CI95 1.20-3.21, p=0.007), and insulin-dependent diabetes mellitus (OR 2.09, CI95 1.05-10.06, p=0.016). Mean follow-up in the matched set was 125 months, IQR 99-162. After matching, in-hospital mortality was higher in the DSWI group (8.1% vs. 2.7% p=0.03), but DSWI was not an independent predictor of long-term survival (adjusted HR 1.5, CI95 0.7-3.2, p=0.33). CONCLUSIONS: The results presented in this report clearly show that post-sternotomy deep wound infection does not influence long-term survival in an adult general cardio-surgical patient population.

A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft

Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway-to-Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only-treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA.

Very long-term survival patterns of young patients treated with radical prostatectomy for high-risk prostate cancer

OBJECTIVE In patients with a long life expectancy with high-risk (HR) prostate cancer (PCa), the chance to die from PCa is not negligible and may change significantly according to the time elapsed from surgery. The aim of this study was to evaluate long-term survival patterns in young patients treated with radical prostatectomy (RP) for HRPCa. MATERIALS AND METHODS Within a multiinstitutional cohort, 600 young patients (≤59 years) treated with RP between 1987 and 2012 for HRPCa (defined as at least one of the following adverse characteristics: prostate specific antigen>20, cT3 or higher, biopsy Gleason sum 8-10) were identified. Smoothed cumulative incidence plot was performed to assess cancer-specific mortality (CSM) and other cause mortality (OCM) rates at 10, 15, and 20 years after RP. The same analyses were performed to assess the 5-year probability of CSM and OCM in patients who survived 5, 10, and 15 years after RP. A multivariable competing risk regression model was fitted to identify predictors of CSM and OCM. RESULTS The 10-, 15- and 20-year CSM and OCM rates were 11.6% and 5.5% vs. 15.5% and 13.5% vs. 18.4% and 19.3%, respectively. The 5-year probability of CSM and OCM rates among patients who survived at 5, 10, and 15 years after RP, were 6.4% and 2.7% vs. 4.6% and 9.6% vs. 4.2% and 8.2%, respectively. Year of surgery, pathological stage and Gleason score, surgical margin status and lymph node invasion were the major determinants of CSM (all P≤0.03). Conversely, none of the covariates was significantly associated with OCM (all P≥ 0.09). CONCLUSIONS Very long-term cancer control in young high-risk patients after RP is highly satisfactory. The probability of dying from PCa in young patients is the leading cause of death during the first 10 years of survivorship after RP. Thereafter, mortality not related to PCa became the main cause of death. Consequently, surgery should be consider among young patients with high-risk disease and strict PCa follow-up should enforce during the first 10 years of survivorship after RP.

Dextran sulfate facilitates anti-CD4 mAb-induced long-term rat cardiac allograft survival after prolonged cold ischemia

Ischemia/reperfusion injury leads to activation of graft endothelial cells (EC), boosting antigraft immunity and impeding tolerance induction. We hypothesized that the complement inhibitor and EC-protectant dextran sulfate (DXS, MW 5000) facilitates long-term graft survival induced by non-depleting anti-CD4 mAb (RIB 5/2). Hearts from DA donor rats were heterotopically transplanted into Lewis recipients treated with RIB 5/2 (20 mg/kg, days-1,0,1,2,3; i.p.) with or without DXS (grafts perfused with 25 mg, recipients treated i.v. with 25 mg/kg on days 1,3 and 12.5 mg/kg on days 5,7,9,11,13,15). Cold graft ischemia time was 20 min or 12 h. Median survival time (MST) was comparable between RIB 5/2 and RIB 5/2+DXS-treated recipients in the 20-min group with >175-day graft survival. In the 12-h group RIB 5/2 only led to chronic rejection (MST = 49.5 days) with elevated alloantibody response, whereas RIB 5/2+DXS induced long-term survival (MST >100 days, p < 0.05) with upregulation of genes related to transplantation tolerance. Analysis of the 12-h group treated with RIB 5/2+DXS at 1-day posttransplantation revealed reduced EC activation, complement deposition and inflammatory cell infiltration. In summary, DXS attenuates I/R-induced acute graft injury and facilitates long-term survival in this clinically relevant transplant model.

Long-term follow-up of lung and heart transplant recipients with pre-transplant malignancies

Concern regarding recurrence of pre-transplant (Tx) malignancy has disqualified patients from Tx. Because this has been poorly studied in lung and heart Tx recipients our aim was to investigate the influence of pre-Tx malignancy on post-Tx recurrence and long-term survival, focusing on pre-operative cancer-free intervals.

Are there accurate predictors of long-term vital and functional outcomes in cardiac surgical patients requiring prolonged intensive care?

BACKGROUND AND OBJECTIVE: The decision to maintain intensive treatment in cardiac surgical patients with poor initial outcome is mostly based on individual experience. The risk scoring systems used in cardiac surgery have no prognostic value for individuals. This study aims to assess (a) factors possibly related to poor survival and functional outcomes in cardiac surgery patients requiring prolonged (> or = 5 days) intensive care unit (ICU) treatment, (b) conditions in which treatment withdrawal might be justified, and (c) the patient's perception of the benefits and drawbacks of long intensive treatments. METHODS: The computerized data prospectively recorded for every patient in the intensive care unit over a 3-year period were reviewed and analyzed (n=1859). Survival and quality of life (QOL) outcomes were determined in all patients having required > or =5 consecutive days of intensive treatment (n=194/10.4%). Long-term survivors were interviewed at yearly intervals in a standardized manner and quality of life was assessed using the dependency score of Karnofsky. No interventions or treatments were given, withhold, or withdrawn as part of this study. RESULTS: In-hospital, 1-, and 3-year cumulative survival rates reached 91.3%, 85.6%, and 75.1%, respectively. Quality of life assessed 1 year postoperatively by the score of Karnofsky was good in 119/165 patients, fair in 32 and poor in 14. Multivariate logistic regression analysis of 19 potential predictors of poor outcome identified dialysis as the sole factor significantly (p=0.027) - albeit moderately - reducing long-term survival, and sustained neurological deficit as an inconstant predictor of poor functional outcome (p=0.028). One year postoperatively 0.63% of patients still reminded of severe suffering in the intensive station and 20% of discomfort. Only 7.7% of patients would definitely refuse redo surgery. CONCLUSIONS: This study of cardiac surgical patients requiring > or =5 days of intensive treatment did not identify factors unequivocally justifying early treatment limitation in individuals. It found that 1-year mortality and disability rates can be maintained at a low level in this subset of patients, and that severe suffering in the ICU is infrequent.

Removal of Limited Nodal Disease in Patients Undergoing Radical Prostatectomy: Long-Term Results Confirm a Chance for Cure

Abstract PURPOSE: In 2003 we reported on the outcomes of 88 patients with node positive disease who underwent radical prostatectomy and pelvic lymph node dissection (median 21 nodes) between 1989 and 1999. Patients with limited nodal disease appeared to have a good chance of long-term survival, even without immediate adjuvant therapy (androgen deprivation therapy and/or radiotherapy). In this study we update the followup in these patients and verify the reported projected probability of survival. MATERIALS AND METHODS: The projected 10-year cancer specific survival probability after the initially reported followup of 3.2 years was 60% for these patients with node positive disease. The outcome has been updated after a median followup of 15.6 years. RESULTS: Of the 39 patients with 1 positive node 7 (18%) remained biochemically relapse-free, 11 (28%) showed biochemical relapse only and 21 (54%) experienced clinical progression. Of these 39 patients 22 (57%) never required deferred androgen deprivation therapy and 12 (31%) died of prostate cancer. All patients with 2 (20) or more than 2 (29) positive nodes experienced biochemical relapse and only 5 (10%) of these 49 experienced no clinical progression. Of these 49 patients 39 (80%) received deferred androgen deprivation therapy. CONCLUSIONS: Biochemical relapse is likely in patients with limited nodal disease after radical prostatectomy and pelvic lymph node dissection, but for 47% of patients this does not imply death from prostate cancer. Patients with 1 positive node have a good (75%) 10-year cancer specific survival probability and a 20% chance of remaining biochemical relapse-free even without immediate adjuvant therapy.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.Leukemia advance online publication, 20 November 2015; doi:10.1038/leu.2015.281.