Search

Contains fulltext : 174816pub.pdf (Publisher’s version ) (Closed access) Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Item does not contain fulltext PURPOSE: Brain MR imaging is essential in the assessment of Chiari II malformation in clinical and research settings concerning spina bifida. However, the interpretation of MR images of the malformation is not always straightforward. Morphometric analyses of the extent of Chiari II malformation may improve the assessment. In an attempt to select appropriate morphometric measures for this purpose, we investigated the interobserver reliability and diagnostic performance of several morphometric measures of Chiari II malformation on MR images. METHODS: Brain MR images of 79 children [26 with open spinal dysraphism, 17 with closed spinal dysraphism, and 36 without spinal dysraphism; mean age 10.6 (SD 3.2; range, 6-16) years] were evaluated. All children had been assessed for Chiari II malformation (defined as cerebellar herniation in combination with open spinal dysraphism; n = 23). Three observers blindly and independently reviewed the MR images for 21 measures of the cerebellum, brainstem, and posterior fossa in three planes. The interobserver reliability was assessed by an agreement index (AI = 1 - RRE) and the diagnostic performance by receiver operating characteristic analyses. RESULTS: Reliability was good for most measures, except for the degree of herniation of the vermis and tonsil. Most values differed statistically significantly between children with and without Chiari II malformation. The measures mamillopontine distance and cerebellar width showed excellent diagnostic performance. CONCLUSIONS: Morphometric measures may reliably quantify the morphological distortions of Chiari II malformation on MR images and provide additional tools to assess the severity of Chiari II malformation in clinical and research settings. 01 juli 2012

Item does not contain fulltext Graft-versus-host disease (GVHD) and fungal infections are frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT). Single nucleotide polymorphisms (SNPs) in genes of the immune system can influence the inflammatory cascade and T cell-driven alloimmune reactions after HSCT, and thus increasing the incidence of GVHD and infectious complications. Here, we investigated the effect of SNPs in IL-23R and CCR6 on posttransplantation outcome in 161 recipients of partially T cell-depleted HSCT. Remarkably, IL-23R SNPs were not associated with clinical outcome, but we found that disparities in the CCR6 tagSNP rs2301436 and SNP rs3093023 are independently associated with the occurrence of chronic GVHD (cGVHD) and invasive fungal disease. In multivariate analysis, patients receiving a transplant from a homozygous rs2301436 G allele donor showed less cGVHD (odds ratio [OR]: 0.16; P = .002), as was the case for a homozygous donor rs3093023 G allele (OR: 0.24; P = .005). In parallel, the GG genotype at rs2301436 in donors was associated with a higher incidence of invasive fungal disease at day 100 after HSCT (OR: 3.59; P = .008). This study shows that CCR6 SNPs can be used to predict clinical outcome, and that polymorphisms in the CCR6 gene may influence T cell-mediated immune reactions after HSCT.

The surgical treatment of spinal metastases is evolving. The major problem is the selection of patients who may benefit from surgical treatment. One of the criteria is an expected survival of at least 3 months. A prediction model has been previously developed. The present study has been performed in order to validate externally the model and to demonstrate that this model can be generalized to other institutions and other countries than the Netherlands. Data of 356 patients from five centers in Germany, Spain, Sweden, and the Netherlands who were treated for metastatic epidural spinal cord compression were collected. Hazard ratios in the test population corresponded with those of the developmental population. However, the observed and the expected survival were different. Analysis revealed that the baseline hazard function was significantly different. This tempted us to combine the data and develop a new prediction model. Estimating iteratively, a baseline hazard was composed. An adapted prediction model is presented. External validation of a prediction model revealed a difference in expected survival, although the relative contribution of the specific hazard ratios was the same as in the developmental population. This study emphasized the need to check the baseline hazard function in external validation. A new model has been developed using an estimated baseline hazard

Item does not contain fulltext BACKGROUND: The 2 most frequently used endoscopic methods to treat Zenker's diverticulum are staple-assisted and CO(2) laser esophagodiverticulostomy. METHODS: The study centered around a retrospective evaluation of 107 patients with Zenker's diverticulum who were treated endoscopically by CO(2) laser (n = 72) or staple-assisted diverticulostomy (n = 35). RESULTS: Patients in the staple-assisted group had a shorter duration of postoperative hospitalization, attributed to earlier oral intake, than patients in the CO(2) laser group. There were no serious postoperative complications in either group. Postoperative fever and emphysema in the neck or mediastinum occurred more frequently in the CO(2) laser group, but this did not lead to any complications. Most patients reported partial or complete relief of their symptoms and there was no significant difference in the number of reoperations between the 2 treatment groups. CONCLUSIONS: Zenker's diverticulum was treated safely and effectively by the 2 endoscopic techniques, but the staple-assisted method seemed to be the most favorable.

Contains fulltext : 87320.pdf (Publisher’s version ) (Closed access) BACKGROUND: Currently, objective tests are lacking that enable the extent and duration of intestinal mucosal damage induced by myeloablative chemotherapy to be determined. To address this problem, we explored a citrulline-based assessment score as this amino acid is a simple quantitative marker of intestinal failure. PATIENTS AND METHODS: From March 2004 to June 2007, citrulline concentrations were determined at baseline and at least once weekly after the start of myeloablative chemotherapy until 30 days thereafter among 94 allogeneic or autologous haematopoietic stem-cell transplant recipients. The patients were divided into three groups according to the regimen they received: (i) carmustine, etoposide, cytarabine and melphalan/high-dose melphalan, (ii) cyclophosphamide and total body irradiation +/- antithymocyte globulin and (iii) idarubicin-containing regimens. Intestinal mucosal damage was described either by level of citrulline on each day, on the basis of different thresholds of citrulline indicating the severity of villous atrophy, or by area under the curve using reciprocal value of 10/citrulline. RESULTS: Regimens that incorporated idarubicin induced the most severe intestinal toxicity. Scores based on the level of citrulline, using severity thresholds, and on the area under the reciprocal curve are able to discriminate between the damage induced by different high-dose chemotherapy regimens. CONCLUSION: A citrulline-based assessment score appears objective, validated, reproducible, reliable, specific and sensitive making it a suitable first choice for measuring and monitoring intestinal mucositis. 01 augustus 2010

Contains fulltext : 89589.pdf (Publisher’s version ) (Closed access) PURPOSE: We determined the potential value of protein profiling of tissue samples by assessing how precise this approach enables discrimination of B-cell lymphoma from reactive lymph nodes, and how well the profiles can be used for lymphoma classification. EXPERIMENTAL DESIGN: Protein lysates from lymph nodes (n=239) from patients with the diagnosis of reactive hyperplasia (n=44), follicular lymphoma (n=63), diffuse large B-cell lymphoma (n=43), mantle cell lymphoma (n=47), and chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma (n=42) were analysed by SELDI-TOF MS. Data analysis was performed by (i) classification and regression tree-based analysis and (ii) binary and polytomous logistic regression analysis. RESULTS: After internal validation by the leave-one-out principle, both the classification and regression tree and logistic regression classification correctly identified the majority of the malignant (87 and 96%, respectively) and benign cases (73 and 75%, respectively). Classification was less successful since approximately one-third of the cases of each group were misclassified according to the histological classification. However, an additional mantle cell lymphoma case that was misclassified as chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma initially was identified based on the protein profile. CONCLUSIONS AND CLINICAL RELEVANCE: SELDI-TOF MS protein profiling allows for reliable identification of the majority of malignant lymphoma cases; however, further validation and testing robustness in a diagnostic setting is needed. 01 mei 2010

Contains fulltext : 80217.pdf (Publisher’s version ) (Closed access) BACKGROUND & AIMS: The success of home parenteral nutrition (HPN) programs is compromised by complications of central venous catheters (CVCs), such as occlusions and bloodstream infections. We performed a retrospective analysis of complication rates of arteriovenous fistulae versus CVCs in patients on long-term HPN. METHODS: Data were collected from 127 consecutive patients who received HPN between January 2000 and October 2006, comprising 344 access years of CVCs and 194 access years of arteriovenous fistulae. We evaluated access-related bloodstream infection and occlusion incidence rates (number of complications per access year) using Poisson-normal regression analysis. Complication incidence rate ratios were calculated by dividing complication incidence rates of CVCs by those of arteriovenous fistulae, adjusting for HPN frequency, medication use, infusion fluid composition, and underlying diseases. RESULTS: Bloodstream infection incidence rates were 0.03/year for arteriovenous fistulae, 1.37/year for long-term CVCs (Port-a-Caths and tunneled catheters), and 3.12/year for short-term CVCs (nontunneled catheters). Occlusion incidence rates were 0.60/year for arteriovenous fistulae, 0.35/year for long-term CVCs, and 0.93/year for shortterm CVCs. Adjusted incidence rate ratios of long-term CVCs over arteriovenous fistulae were 47 (95% confidence interval, 19-117) for bloodstream infections and 0.53 (95% confidence interval, 0.31-0.89) for occlusions. CONCLUSIONS: The occlusion incidence rate was higher for arteriovenous fistulae than for certain types of CVCs. The incidence rate of the most serious access-related complication (bloodstream infections) was much lower for arteriovenous fistulae than for all types of CVCs. Thus, arteriovenous fistulae are safe and valuable alternatives to CVCs for patients requiring long-term HPN.

Contains fulltext : 70727.pdf (Publisher’s version ) (Closed access) OBJECTIVE: This study aimed to determine the diagnostic application of multiplex ligation-dependent probe amplification (MLPA) as a stand-alone test for targeted detection of common chromosomal aneuploidies (i.e. 13, 18, 21, X and Y) in amniotic fluid cells in routine prenatal clinical practice. METHODS: In this evaluation study, the MLPA test using kit P095 was performed on 1000 consecutive amniotic fluid samples and the results obtained were compared with traditional karyotyping (TK), the gold standard. RESULTS: The absolute specificity and sensitivity of the MLPA test were 100%. The test yielded a rapid reporting time: 94% within three working days and 5% within seven working days. The test failure rate was 0.8%. The percentage of abnormalities undetectable using this specific test was 2.4%: abnormal foetal ultrasound (N=9), increased risk first trimester screening (N=2), advanced maternal age (N=3) or other reason for referral (N=10). These abnormalities can be categorised in clinically significant (N=8), clinically uncertain (N=4) and clinically nonsignificant (N=12). CONCLUSIONS: MLPA P095 is suitable as a stand-alone test for the rapid and efficient detection of the most common chromosomal aneuploidies in routine prenatal clinical practice. A flow chart for integrating the MLPA test into the cytogenetic laboratory workflow is presented.

Contains fulltext : 52398.pdf (Publisher’s version ) (Closed access) BACKGROUND: The surgical treatment of spinal epidural metastasis is evolving. To be a surgical candidate, a patient should have a life expectancy of at least 3 months. Estimation of survival by experienced specialists has proven to be unreliable. METHODS: The Cox proportional hazards model was used to make a prediction model. To validate the model, Efron optimism correction by bootstrapping was performed. Retrospective data of patients treated for a spinal metastasis were used. Possible predictive factors were defined based on clinical experience and the literature. Statistical methods and clinical knowledge were also used to reveal an optimal set of predictors of survival. Data from patients treated at the Department of Radiation Oncology for spinal metastasis between 1998 and 2005 were evaluated. RESULTS: The case notes of 219 patients form the base of this study. In the final model, only 5 variables were required to predict the survival of a patient with spinal metastasis: sex, location of the primary lesion, intentional curative treatment of the primary tumor, cervical location of the spinal metastasis, and Karnofsky performance score. Examples with different predictors are given. The R(2) (N) index of Nagelkerke was 0.36 (95% confidence interval [95% CI], 0.28-0.48) and the c-index 0.72 (95% CI, 0.68-0.77). CONCLUSIONS: A reliable and simple model with which to predict the survival of a patient with spinal epidural metastasis is presented. Without the need for extensive investigations, survival can be predicted and only 5 easily obtainable parameters are required.

Contains fulltext : 80406.pdf (Publisher’s version ) (Closed access) B-cell chronic lymphocytic leukemia (CLL) is characterized by a highly variable clinical course. Characteristic genomic abnormalities provide clinically important prognostic information. Because karyotyping and fluorescence in situ hybridization (FISH) are laborious techniques, we investigated the diagnostic efficacy of the more recently developed multiplex ligation-dependent probe amplification (MLPA) technique. MLPA and interphase FISH data of 88 CLL patients were compared for loci encompassing the 13q14 region, chromosome 12, and the ATM (11q22) and TP53 (17p13) genes. We found a perfect correlation, provided that the abnormal clone was present in at least 10-20% of the cells. Because multiple loci and multiple probes per locus were included in the MLPA assay, additional abnormalities not covered by the FISH probes were detected. Furthermore, in 13 cases deletions partly covering the 13q14.3 locus were observed, including three deletions that remained undetected by FISH. All the deletions included the noncoding RNA locus DLEU1 (previously BCMS), which is considered to be the most likely CLL-associated candidate tumor suppressor gene within the 13q14 region. We conclude that MLPA serves as a comprehensive and reliable technique for the simultaneous identification of different clinically relevant and region-specific genomic aberrations in CLL.

Contains fulltext : 51865.pdf (Publisher’s version ) (Closed access) AIMS: The objective of this study is to establish factors associated with death after diagnosis of Ebstein's anomaly (EA) during childhood and adolescence. METHODS AND RESULTS: This study is a retrospective chart review. All paediatric patients were diagnosed with EA and followed in tertiary-care university hospitals between 1980 and 2005. Factors associated with death were obtained using the Cox regression and log-rank tests. Of the 93 patients with EA, 18 (19%) died and 75 (81%) survived. The median age at EA diagnosis and follow-up was 0 (range 0-162) and 86 months (range 0-216), respectively. After 35 months of diagnosis, the Kaplan-Meier survival probability remains stable at 80%. Young age at presentation (< or =12 months), hepatomegaly, the need for medication (diuretics and Prostin) and mechanical ventilation at presentation, pulmonary valve defects (defined as moderate-to-severe pulmonary stenosis and pulmonary atresia), patent arterial duct, and ventricular septal defect were significantly associated with death. CONCLUSION: The overall survival of patients with EA during childhood and adolescence has dramatically improved when compared with earlier reports.

Contains fulltext : 47450.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To study the role of eustachian tube function in the development of recurrent otitis media with effusion (OME) in children treated with tympanostomy tubes for OME. DESIGN: Prospective cohort study. SETTING: Three academic and general hospitals. PATIENTS: Children aged 2 to 7 years with a first clinical episode of OME that persisted for at least 3 months; 136 (81%) of 168 eligible children participated. All children received tympanostomy tubes for bilateral OME at study entry. MAIN OUTCOME MEASURE: Recurrence of OME within 6 months of tube extrusion. RESULTS: No statistically significant differences were present in eustachian tube function test results between ears that developed recurrent OME and those that did not. The difference in passive ventilatory function between ears with and without OME recurrence was 10 daPa (95% confidence interval, -24 to 43 daPa) for opening pressure and -3 daPa (95% confidence interval, -18 to 11 daPa) for closing pressure. The overall difference in the proportion of ears with and without OME recurrence that could not equilibrate positive and negative applied pressures was 12% (95% confidence interval, -2% to 26%). The proportions of ears with and without OME recurrence that induced negative pressure in the middle ear by forcefully sniffing were 22% and 31%, respectively (P = .75). CONCLUSION: Measurement of ventilatory and protective eustachian tube function using the forced response test, the pressure equilibration test, and the sniff test has no value in predicting whether children have an increased risk of OME recurrence.