Side effects of proton beam therapy of choroidal melanoma in dependence of the dose to the optic disc and the irradiated length of the optic nerve

Graefe's Archive for Clinical and Experimental Ophthalmology - To analyze the impact of the dose to the optic disc and the irradiated length of the optic nerve on radiation-induced optic...     

Immune reconstitution and cytomegalovirus infection after allogeneic stem cell transplantation: the important impact of in vivo T cell depletion

We analyzed cytomegalovirus (CMV) infection risk factors and immune reconstitution kinetics in 89 patients after allogeneic stem cell transplantation (allo-SCT). The use of alemtuzumab for in vivo T cell depletion (TCD) had, besides the donor/recipient CMV serostatus, the strongest influence on the CMV infection risk in univariate and multivariate analyses. In comparison to without use of in vivo TCD, the CMV infection risk [hazard ratio (HR)] was 4.82-fold after TCD with alemtuzumab, but only 1.40-fold after TCD with antithymocyte globulin (ATG). Alemtuzumab strongly depressed CD4⁺ and CD8⁺ T cell reconstitution, whereas ATG only delayed CD4⁺ T cell reconstitution. Considering the reconstitution kinetics of CD4⁺ and CD8⁺ T cells, CMV-specific CD8⁺ T cells, NK cells and the IgG concentration, only a low day +60 NK cell count (≤161 versus >161/μl) was significantly associated with CMV infection development (HR 2.92, p = 0.034). CMV-specific CD8⁺ T cells were detected in 57% of patients with a CMV-seropositive donor, but in none of the patients with a CMV-seronegative donor on day +30 (p = 0.01). Our data indicate that the type of in vivo TCD (alemtuzumab or ATG) differentially influences both the CMV infection risk and CD4⁺/CD8⁺ T cell reconstitution kinetics in patients after allo-SCT.     

Preconceptional factors associated with very low birthweight delivery in East and West Berlin: a case control study

Background  

Very low birthweight, i.e. a birthweight < 1500 g, is among the strongest determinants of infant mortality and childhood morbidity. To develop primary prevention approaches to VLBW birth and its sequelae, information is needed on the causes of preterm birth, their personal and social antecedents, and on conditions associated with very low birthweight. Despite the growing body of evidence linking sociodemographic variables with preterm delivery, little is known as to how this may be extrapolated to the risk of very low birthweight.     

Reduction of wound infections in laparoscopic-assisted colorectal resections by plastic wound ring drapes (REDWIL)?—a randomized controlled trial

Introduction

Surgical site infections (SSIs) are frequent complications in colorectal surgery and may lead to burst abdomen, incisional hernia, and increased perioperative costs. Plastic wound ring drapes (RD) were introduced some decades ago to protect the abdominal wound from bacteria and reduce SSIs. There have been no controlled trials examining the benefit of RD in laparoscopic colorectal surgery. The Reduction of wound infections in laparoscopic assisted colorectal resections by plastic wound ring drapes (REDWIL) trial was thus designed to assess their effectiveness in preventing SSIs after elective laparoscopic colorectal resections.

Materials/methods

REDWIL is a randomized controlled monocenter trial with two parallel groups (experimental group with RD and control group without RD). Patients undergoing elective laparoscopic colorectal resection were included. The primary endpoint was SSIs. Secondary outcomes were colonization of the abdominal wall with bacteria, reoperations/readmissions, early/late postoperative complications, and cost of hospital stay. The duration of follow-up was 6?months.

Results

Between January 2008 and October 2010, 109 patients were randomly assigned to the experimental or control group (with or without RD). Forty-six patients in the RD group and 47 patients in the control group completed follow-up. SSIs developed in ten patients with RD (21.7?%) and six patients without RD (12.8?%) (p?=?0.28). An intraoperative swab taken from the abdominal wall was positive in 66.7?% of patients with RD and 57.5?% without RD (p?=?0.46). The number of species cultured within one swab was significantly higher in those without RD (p?=?0.03). The median total inpatient costs including emergency readmissions were 3,402?±?4,038 € in the RD group and 3,563?±?1,735 € in the control group (p?=?0.869).

Conclusions

RD do not reduce the rate of SSIs in laparoscopic colorectal surgery. The inpatient costs are similar with and without RD.     

Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer

Purpose  CCR6 is expressed in various tumors and has been implicated in the process of tumor progression and metastasis. Its chemokine ligand, CCL20, is present in different tissues including lymph nodes, but also the normal prostate. This study was performed to investigate a potential relationship between CCR6 and CCL20 expression and features of human prostate cancer (PCA) at time of primary treatment. Methods  Immunohistochemistry was used to detect CCR6 and CCL20 expression in archival tissue blocks of 80 PCA cases of various tumor grades and stages. Evaluation was semiquantitatively by visual scoring and quantitatively by digital image analysis (DIA). CCR6 and CCL20 expression was compared with Gleason score, stage, perineural invasion, nodal metastasis, age, and preoperative serum prostate-specific antigen (PSA) level by univariate and multivariate analyses. Results  Staining intensity of CCR6 in tumor cells varied considerably, with it being: weak in 21 tumors (26.2%), intermediate in 44 (55.0%), and strong in 15 (18.8%), with 3.6-log differences in DIA measurements. CCL20 expression was absent in eight tumors (10.0%), weak in 41 (51.2%), intermediate in 23 (28.8%), and strong in eight (10.0%). CCR6 and CCL20 expression did not correlate. CCR6 expression was associated with T-category (P < 0.0005), Gleason score (P = 0.003), and lymph node metastasis (P = 0.002). Conclusions  Expression levels of CCR6 in PCA were associated with clinical and pathologic features of more advanced and aggressive prostate cancer. Thus, CCR6 may directly or indirectly be involved in tumor progression and should be evaluated as novel candidate target molecule for specific treatment interventions.     

Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell transplantation

Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation (HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (<1 microg/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells (>30%). However, the number of tumor reactive (CD107a+) NK cells was 13.16 per mul and 1.15 per microl (mean) in patients receiving T-cell depletion with 6 mg/kg thymoglobulin and in patients receiving 100 mg alemtuzumab, respectively (P=0.02). Although thymoglobulin and alemtuzumab are equally NK cell toxic in vitro, the recovery of NK cell frequency and anti-tumor reactivity is reduced in recipients of alemtuzumab. Our findings can be explained by a longer half-life of alemtuzumab as compared to active thymoglobulin under therapeutic conditions. Prolonged immunosuppression with increased risk of infections and tumor relapse are a potential threat to patients undergoing HCST and receiving alemtuzumab as T-cell depletion.     

Measurable learning effects after a 1-week skills course in digestive surgery

Aim  

The aim of this study was to assess the learning effects of a surgical skills course focussed on theoretical knowledge, anastomosis techniques and practical suturing skills in digestive surgery.     

Prognostic implications of NOTCH1 and FBXW7 mutations in adult acute T-lymphoblastic leukemia

Background

NOTCH1 mutations have been associated with a favorable outcome in pediatric acute T-lymphoblastic leukemia. However, the results of studies on the prognostic significance of NOTCH1 mutations in adult T-lymphoblastic leukemia remain controversial.

Design and Methods

Here we have investigated the prognostic impact of mutations in the NOTCH1 pathway, in particular, the NOTCH1 and FBXW7 genes, in a large cohort of adult patients with T-lymphoblastic leukemia (n=126). We determined the occurrence of mutations in NOTCH1 and FBXW7 by DNA amplification and direct sequencing of polymerase chain reaction products.

Results

Mutations were identified in 57% and 12% of the NOTCH1 and FBXW7 genes, respectively. The characteristics of patients carrying NOTCH1 and/or FBXW7 (NOTCH1-FBXW7) mutations were similar to those with wild-type genes. Patients with NOTCH1-FBXW7 mutations more often showed a thymic immunophenotype (p=0.001). In the overall cohort, no significant differences were seen in the complete remission or event-free survival rates between patients with mutated or wild-type NOTCH1-FBXW7 (p=0.39).

Conclusions

NOTCH1 and FBXW7 mutations were not predictive of outcome in the overall cohort of adult patients with T-lymphoblastic leukemia, but there was a trend towards a favorable prognostic impact of NOTCH1-FBXW7 mutations in the small subgroup of patients with low-risk ERG/BAALC expression status. Our findings further confirm the high frequency of NOTCH1 mutations in adult T-lymphoblastic leukemia.