Are computed tomography-based measures of specific abdominal muscle groups predictive of adverse outcomes in older cancer patients?

PURPOSE: It is unknown whether computed tomography (CT)-based total abdominal muscle measures are representative of specific abdominal muscle groups and whether analysis of specific abdominal muscle groups are predictive of the risk of adverse outcomes in older cancer patients. METHODS: Retrospective single-center cohort study in elective colon cancer patients aged ≥65 years. CT-based skeletal muscle (SM) surface area, muscle density and intermuscular adipose tissue (IMAT) surface area were determined for rectus abdominis; external- and internal oblique and transversus abdominis (lateral muscles); psoas; and erector spinae and quadratus lumborum (back muscles). Outcomes were defined as severe postoperative complications (Clavien-Dindo score >2) and long-term survival (median follow-up 5.2 years). RESULTS: 254 older colon cancer patients were included (median 73.6 years, 62.2% males). Rectus abdominis showed the lowest SM surface area and muscle density and the back muscles showed the highest IMAT surface area. Psoas muscle density, and lateral muscle density and percentage IMAT were associated with severe postoperative complications independent of gender, age and cancer stage. CONCLUSIONS: CT-based total abdominal muscle quantity and quality do not represent the heterogeneity that exists between specific muscle groups. The potential added value of analysis of specific muscle groups in predicting adverse outcomes in older (colon) cancer patients should be further addressed in prospective studies.

Occupational exposure of pharmacy technicians and cleaning staff to cytotoxic drugs in Dutch hospitals.

Many studies into surface contamination of hospital environments have demonstrated that occupational exposure to cytotoxics through the dermal route remains a possible risk. In this study, we assess the actual dermal exposure of the hands of pharmacy technicians and cleaning personnel in a panel of hospitals performing tasks that pose a risk of exposure. We compare the dermal exposure to a tentative limit value for cyclophosphamide. Pharmacy technicians and cleaning personnel were asked for hand rinsing after performance of nine tasks previously identified as posing a risk of occupational exposure. All samples were analyzed for the presence and quantity of eight antineoplastic drugs. By using data on both the frequency of the performance of the tasks and the measured dermal contamination during these tasks, weekly exposure to the marker drug (cyclophosphamide) was calculated. In five Dutch hospitals, 70 hand rinse samples and 8 blanks were collected. These were analyzed and results were used to calculate weekly exposure. The tentative limit value used was 0.74 µg of cyclophosphamide. For cleaning personnel, all results remained below this threshold value. For pharmacy technicians, the compounding itself also remained well below the limit; however, the task involving preparatory work, as well as the checking of compounded drugs, had a 13% chance of exceeding the limit. All of the highest values were found when employees were not wearing gloves on these tasks. Cleaning personnel and pharmacy technicians compounding cytotoxic drugs in our study were sufficiently protected from occupational exposure. In contrast, pharmacy technicians who perform preparatory and finishing tasks (before and after the actual compounding) are not protected enough when they do not wear gloves.

Skeletal muscle mass and quality as risk factors for postoperative outcome after open colon resection for cancer.

BACKGROUND: The prevalence of colorectal cancer in the elderly is increasing and, therefore, surgical interventions with a risk of potential complications are more frequently performed. This study investigated the role of low skeletal muscle mass (sarcopenia), muscle quality, and the sarcopenic obesity as prognostic factors for postoperative complications and survival in patients with resectable colon cancer. METHODS: We conducted a retrospective chart review of 91 consecutive patients who underwent an elective open colon resection for cancer with primary anastomosis between 2011 and 2013. Skeletal muscle mass was measured as total psoas area (TPA) and total abdominal muscle area (TAMA) at three anatomical levels on the preoperative CT scan. Skeletal muscle quality was measured using corresponding mean Hounsfield units (HU) for TAMA. Their relation with complications (none vs one or more), severe complications, and survival was analyzed. RESULTS: The study included 91 patients with a mean age of 71.2 ± 9.7 years. Complications were noted in 55 patients (60 %), of which 15 (16.4 %) were severe. Lower HU for TAMA, as an indicator for impaired skeletal muscle quality, was an independent risk factor for one or more complications (all P ≤ 0.002), while sarcopenic obesity (TPA) was an independent risk factor for severe complications (all P ≤ 0.008). Sarcopenia was an independent predictor of worse overall survival (HR 8.54; 95 % confidence interval (CI) 1.07-68.32). CONCLUSION: Skeletal muscle quality is a predictor for overall complications, whereas sarcopenic obesity is a predictor for severe postoperative complications after open colon resection for cancer. Sarcopenia on itself is a predictor for worse overall survival.

Hepatocellular carcinoma after danazol treatment for hereditary angio-oedema.

Hereditary angio-oedema is characterised by recurrent episodes of laryngeal, intra-abdominal, facial or peripheral oedema. Danazol can be used as prophylaxis for recurrent attacks. Hepatotoxicity is a recognised adverse effect of danazol. We report an exceptional case of a danazol-induced hepatocellular carcinoma in a 75-year-old patient with hereditary angio-oedema.

Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia.

t(1;22) is the principal translocation of acute megakaryoblastic leukemias. Here we show this chromosomal rearrangement to result in the fusion of two novel genes, RNA-binding motif protein-15 (RBM15), an RNA recognition motif-encoding gene with homology to Drosophila spen, and Megakaryoblastic Leukemia-1 (MKL1), a gene encoding an SAP (SAF-A/B, Acinus and PIAS) DNA-binding domain.

Spontaneous blastomere fusion after freezing and thawing of early human embryos leads to polyploidy and chromosomal mosaicism.

The incidence of blastomere fusion after cryopreservation of early human embryos (day 2 and day 3) was investigated using the standard propanediol technique. The process of fusion was observed in all developmental stages (from 2 to 10 cells) and the frequency of this event was 4.6% in day 2 (41/889) and 1.5% in day 3 (10/646) embryos that survived the thawing (embryos with 50-100% intact cells). Fusion of two, and occasionally of several, blastomeres resulted in the formation of multinucleated hybrid cells, which clearly indicated that the ploidy of these newly created cells had been altered. This event, depending on the number of fused cells per embryo, transformed the embryos into either entirely polyploid embryos (complete fusion at 2- or 3-cell stage) or into mosaics being a mixture of polyploid and normal cells. Chromosomal preparations of embryos affected by blastomere fusion indicated the presence of tetraploid mitotic plates. Also, fluorescence in-situ hybridization (FISH) analysis using DNA probes targeting unique sequences on chromosomes 9, 15, 17 and 22 indicated the existence of tetraploid and diploid fluorescence signals in the interphase nuclei within mosaics. Therefore, observations on live and fixed embryos suggested that tetraploid (4n) or hexaploid (6n) and tetraploid-diploid or more complex aberrations of ploidy might be formed as a consequence of blastomere fusion. Furthermore, this demonstrates that freezing and thawing may induce numerical chromosomal changes in human embryos.

Clonal heterogeneity of dendritic cells derived from patients with chronic myeloid leukemia and enhancement of their T-cells stimulatory activity by IFN-alpha.

Adoptive immunotherapy in form of donor leukocyte infusions is effective in a significant number of patients with chronic myeloid leukemia (CML) that have relapsed after allogeneic bone marrow transplantation (BMT). However, the therapy is associated with clinically significant side effects such as graft-versus-host disease (GVHD) and bone marrow (BM) hypoplasia that may be avoided through the administration of T cells with specific antileukemic activity. Dendritic cells (DC) functioning as potent antigen presenting cells (APC) may play an important role in the generation of T cells with specificity against CML. We examined a subpopulation of CD1a+/CD14- DC generated in vitro from BM of normal subjects and patients with CML using granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha) and interleukin-4 (IL-4). These DC derived from both the BM of normal subjects and of patients with CML, differentiated and matured in culture in a similar way. However, DC derived from patients with CML, displayed decreased activity when tested with allogeneic T cells in a mixed lymphocyte reaction (MLR). Addition of interferon-alpha (IFN-alpha) to DC cultures significantly upregulated the expression of major histocompatibility complex (MHC) molecules (class I and class II) and costimulatory molecules (B7.1 and B7.2) on DC from normal donors and CML patients. However, DC grown from CML patients required a higher concentration of IFN-alpha. IFN-alpha also significantly improved the capacity of CML DC to stimulate T-lymphocyte responses. Fluorescence in situ hybridization (FISH) showed that only some CD1a+/CD14- DC derived from BM of patients with CML expressed the bcr/abl fusion gene. Incubation with INF-alpha decreased the proportion of bcr/abl positive DC.

Frequent monoallelic loss of D13S319 in multiple myeloma patients shown by interphase fluorescence in situ hybridization.

Deletions or monosomy of chromosome 13 are frequent in multiple myeloma (MM). A candidate tumor suppressor gene might reside telomeric of the retinoblastoma gene (RBl) at band 13q14 and to play a role in B cell neoplasm. The D13S319 locus, between RB1 and D13S25 loci at 13q14 is the most commonly deleted marker in chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL). We evaluated the D13S319 locus in 24 MM cases by fluorescence in situ hybridization (FISH). We observed monosomy for D13S319 in 6/20 (30%) MM patients with an apparently normal karyotype. As expected, in four karyotypically abnormal MM cases with partial or complete monosomy for chromosome 13, all of them had monoallelic loss of D13S319. Our results indicated that the loss of D13S319 is commonly found in MM, even at diagnosis, and is more frequent than predicted based on conventional cytogenetic analysis of metaphase spreads. This finding implicates a candidate tumor suppressor gene at 13q14 in the pathogenesis of MM.