Bone Mineral Density Is a Predictor of Mortality in Female Patients with Cholangiocellular Carcinoma Undergoing Palliative Treatment.

BACKGROUND: Cholangiocellular adenocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts. Its general prognosis is poor as therapeutic options are limited. Many patients present with advanced stages of disease, and palliative chemotherapy remains the only treatment option. Prognostic markers to assess the outcome of chemotherapeutic treatment in CCA are limited. We therefore evaluated bone mineral density (BMD) as a prognostic tool in patients with advanced CCA. PATIENTS AND METHODS: We included 75 patients with advanced CCA that were treated at our academic tumor center. Prior to treatment, bone mineral density was analyzed at the first lumbar vertebra using routine CT scans in the venous phase and the local PACS (IntelliSpace PACS, Philips, Amsterdam, The Netherlands). RESULTS: BMD was not significantly different between male and female patients but decreased with age. Patients with BMD above 167 HU have a significantly improved overall survival (474 days vs. 254 days; log-rank X2(1) = 6.090; p = 0.014). The prognostic value of BMD was confirmed using univariate (HR 2.313 (95%CI: 1.170-4.575); p = 0.016) and multivariate (HR 4.143 (95%CI: 1.197-14.343); p = 0.025) Cox regression analyses. Subgroup analysis revealed that the prognostic value of BMD was only present in female patients and not in male patients, suggesting sex-specific differences. CONCLUSIONS: Our data suggest that BMD is a valuable, easily accessible, and independent prognostic marker for overall survival in patients with advanced CCA. Furthermore, subgroup analysis showed the sex specificity of this marker, which demonstrated relevance only in female patients.

Sarcopenia Predicts Cancer Mortality in Male but Not in Female Patients Undergoing Surgery for Cholangiocellular Carcinoma.

INTRODUCTION: Surgery represents the only curative treatment option for patients with cholangiocarcinoma. However, complete tumor resection requires extensive surgery in many patients, and it is still debated which patients represent the ideal candidates for such therapy in terms of overall survival. Sarcopenia has been associated with an adverse outcome for various malignancies, but its role in the context of patients undergoing tumor resection for cholangiocellular adenocarcinoma (CCA) is only poorly understood. Here, we evaluated the role of sarcopenia in the outcome of CCA patients undergoing radical tumor resection. METHODS: Pre-operative CT scans were used to assess the skeletal muscle index (L3SMI) as well as the psoas muscle index (L3PMI) in n = 76 patients receiving curative intended surgery for CCA. L3SMI and L3PMI were correlated with clinical and laboratory markers. RESULTS: Patients with a skeletal muscle index or psoas muscle index above an established ideal cut-off (54.26 and 1.685 cm2/m2) showed a significantly better overall survival in Kaplan-Meier Curve analyses (L3SMI: 1814 days (95% CI: 520-3108) vs. 467 days (95% CI: 225-709) days; log rank X2(1) = 7.18, p = 0.007; L3PMI: 608 days (95% CI: 297-919) vs. 87 days (95% CI: 33-141), log rank X2(1) = 18.71; p < 0.001). Notably, these findings, especially for L3PMI, were confirmed in univariate (L3SMI: HR 0.962 (0.936-0.989); p = 0.006; L3PMI: HR 0.529 (0.366-0.766); p ≤ 0.001) and multivariate Cox regression analyses. Further analyses revealed that the prognostic value of both L3SMI and L3PMI was restricted to male patients, while in female patients survival was independent of the individual muscle mass. CONCLUSION: Measurement of muscle mass from preoperative CT scans represents an easily obtainable tool to estimate patient prognosis following curative surgery. The prognostic value was restricted to male patients, while in female patients these parameters did not reflect the patient outcome.

Sarcopenia and Myosteatosis as Prognostic Markers in Patients with Advanced Cholangiocarcinoma Undergoing Palliative Treatment.

BACKGROUND: Cholangiocarcinoma (CCA) represents the second most common primary liver cancer and is characterized by a very poor outcome, but reliable prognostic markers are largely missing. Sarcopenia, the progressive loss of muscle mass and strength, as well as myosteatosis have been associated with an unfavorable outcome in several clinical conditions, including cancer. Here, we evaluated the prognostic relevance of sarcopenia and myosteatosis using routine abdominal CT (computed tomography) scans in advanced stage CCA patients undergoing palliative treatment. METHODS: Routine abdominal CT scans were used to assess the skeletal muscle and the psoas muscle index (L3SMI/L3PMI) at the level of the third lumbar vertebra as radiological indices for sarcopenia as well as the mean skeletal muscle attenuation (MMA) as a surrogate for myosteatosis. Results were correlated with clinical data and outcomes. RESULTS: Using a calculated optimal cut-off value of 71.95 mm2/cm, CCA patients with an L3SMI value below this cut-off showed a significantly reduced median overall survival (OS) of only 250 days compared to 450 days in patients with a higher L3SMI. Moreover, the median OS of CCA patients with an L3PMI above 6345 mm2/cm was 552 days compared to 252 days in patients with a lower L3PMI. Finally, CCA patients with an MMA above 30.51 Hounsfield Units survived significantly longer (median OS: 430 days) compared to patients with an MMA value below this ideal cut-off (median OS: 215 days). The prognostic relevance of L3SMI, L3PMI, and MMA was confirmed in uni- and multivariate Cox regression analyses. CONCLUSION: Routine abdominal CT scans represent a unique opportunity to evaluate sarcopenia as well as myosteatosis in advanced CCA patients. We identified the L3SMI/L3PMI as well as the MMA as negative prognostic factors in CCA patients undergoing palliative therapy, arguing that the "opportunistic" evaluation of these parameters might yield important clinical information in daily routine.

Sporosarcina pasteurii use in extreme alkaline conditions for recycling solid industrial wastes.

The ureolytic bacteria are one of the most efficient organisms able to produce high amounts of carbonate that easily react with the free calcium ions from the environment. Sporosarcina pasteurii, a robust microbe in alkaline environments, was tested in this work for its potential use in an eco-cementation process that involves the biomediated calcite precipitation (BCP). Bacterial behavior in extreme alkaline environment (pH values of 9-13) was tested in controlled laboratory conditions and in the presence of solid industry wastes, such as Cement Kiln Dust (CKD) and Lime Kiln Dust (LKD), by evaluating the enzymatic activity and the calcite precipitation capacity. Grain consolidation potential of S. pasteurii was tested for one type of CKD mixed with ground granulated blast-furnace slag (GGBS), with possible bioclogging and biocementation applications. The results revealed the formation of stable biocalcite in the presence of CKD, with a performance depending on the pH-value and free calcium ion content. The BCP induced by S. pasteurii and the recycling of solid wastes, such as CKD with high lime content, is a promising way for different bioclogging and biocementation applications, with benefits in construction costs and reduction of environmental pollution.

Alternative nutrient sources for biotechnological use of Sporosarcina pasteurii.

The potential use of Sporosarcina pasteurii in possible biotechnological applications on a large scale (ground improvement, consolidation of building structures and ornamental stone, or in developing bio-materials for the building industry), is based on its ability to produce high amounts of carbonate in a short period of time via urea hydrolysis. Industrial biomass production would have a low environmental impact and would be most economical if the standard growth media could be replaced with alternative nutrient sources, such as byproducts or wastes from other industries, or other low cost ingredients. The use of cost effective ingredients must guarantee ureolytic activities and growth conditions that are comparable to those resulting from the standard nutrient medium. In this work, three types of alternative media were tested for growing the ureolytic active bacteria S. pasteurii: (1) alternative nutrient sources such as industrial wastes resulting from the dairy and brewery industries, (2) fertilizer urea as an alternative urea substitute, and (3) different types of poultry manure based fertilizers as nutrient and urea substitutes. The comparison between the standard media, the nutrient alternatives and urea substitutes was possible by taking the protein concentration and nitrogen content into account. Bacterial activity was evaluated in terms of biomass changes over time (CFU, optical density, ATP measurements) and indirect estimation of the enzyme production (Nessler assay, conductivity measurement). The results revealed that some of the dairy wastes tested, such as whey and buttermilk, are potential alternative nutrients for bacterial development, while the urea fertilizer is perfectly suitable as an economical substitute for pure laboratory grade urea.

In situ sonochemical synthesis of ZnO particles embedded in a thermoplastic matrix for biomedical applications.

Zinc oxide particles were synthesized and dispersed in situ in a polystyrene (PS) matrix using ultrasound. PS ultrasonic degradation was investigated at different polymer concentrations in organic solvent in contact with aqueous media prior to the particle synthesis. Decrease in weight-average molecular weight (Mw) was strongly dependent on polymer concentration in organic solvent and sonication time: degradation occurred less at higher polymer concentration, yet increased with longer times of more than 30min. The ZnO particles with a 800nm flower-like morphology were dispersed in the polystyrene matrix in situ; the composite presented both a lower average molecular weight (Mw) and lower number average molecular weight Mn when compared to pristine polystyrene, however thermal degradation temperature and Young's modulus were similar to the pristine polystyrene. The composite prepared in situ presented lower particle aggregation in comparison with ZnO commercially dispersed with ultrasound under the same conditions. Antibacterial activity of the ZnO/PS coating was tested against Escherichia coli (Gram-negative bacteria; DMS No. 10290) by evaluating bacterial growth inhibition after 20h on contact with the film surface. The results indicated that bacterial growth was inhibited in the medium in contact with the composite prepared in situ compared to the film of composite prepared by mixing and the pristine PS. This study showed the potential use of ZnO/PS composite prepared in situ as antibacterial coatings.