Purpose: Obesity is associated with increased incidence and mortality in rectal cancer (RC). However, an obesity paradox in the sense of a protective effect of obesity is discussed controversially. ...We evaluated whether adipose tissue distribution has an impact on medical (MC) and surgical complications (SC) after RC surgery. Methods: A total of 296 RC patients underwent oncological surgery and multidetector CT with quantification of total (TAT), visceral (VAT), and subcutaneous adipose tissue (SAT). Logistic regressions on SC (anastomotic leakage n = 26, wound infection n = 58, bleeding n = 12, abscess n = 32, bladder dysfunction n = 24, burst abdomen n = 10), and MC (pulmonary n = 22, cardiac n = 18, urinary tract infection n = 9, sepsis n = 5) were performed. Results: High pelvic VAT was associated with reduced risk for overall SC (OR = 0.915, p = 0.012) and anastomotic leakage (OR = 0.587, p = 0.024, CI: 0.369/0.934). In contrast, CT-quantified obesity was associated with increased risk for wound infection, bladder dysfunction, burst abdomen, overall MC, and cardiac complications (ORs up to 1.423). BMI was not associated with any SC or MC. Conclusion: An obesity paradox with a protective effect of CT-quantified adipose tissue was confirmed for anastomotic leakage and overall SC. In contrast, high adipose tissue was associated with higher risk for other SC and MC. These results show a more complex influence of body composition on MC and SC. CT-quantified obesity is able to provide deeper insights to explain the obesity paradox beyond BMI.
Metabolomics is a valuable tool for biomarker screening of colorectal cancer (CRC). In this study, we profiled the urinary metabolomes of patients enrolled in a prospective patient cohort (ColoCare). ...We aimed to determine changes in the metabolome of the longer clinical follow-up and ascertain candidate markers with possibly prognostic significance. In total, 199 urine samples from CRC patients prior to surgery (n = 97) or 1–8 days post-surgery (n = 12), and then after 6 (n = 52) and 12 months (n = 38) were analyzed using both GC–MS and
1
H-NMR. Both datasets were analyzed separately with built in uni- and multivariate analyses of Metaboanalyst 2.0. Furthermore, adjusted linear mixed effects regression models were constructed. Many concentrations of the metabolites derived from the gut microbiome were affected by CRC surgery, presumably indicating a tumor-induced shift in bacterial species. Associations of the microbial metabolites with disease stage indicate an important role of the gut microbiome in CRC. We were able to differentiate the metabolite profiles of pre-surgery CRC patients from those at any post-surgery timepoint using a multivariate model containing 20 marker metabolites (AUCROC = 0.89; 95 % CI 0.84–0.95). This is one of the first metabolomic studies to follow CRC patients in a prospective setting with repeated urine sampling over time. We were able to confirm markers initially identified in case–control studies and metabolites which may represent prognostic biomarker candidates of CRC.
Background Ventral incisional hernia is the most common long-term complication after an abdominal operation. Among newly diagnosed colorectal cancer patients, we screened the preoperative plasma ...proteome to explore predictive markers for the development of an incisional hernia. Methods We utilized preoperative plasma samples of 72 newly diagnosed colorectal cancer patients who underwent midline incision for tumor resection between 2010 and 2013. A total of 21 patients with incisional hernia occurrence were matched with 51 patients with at least 18 months follow-up without an incisional hernia by sex, age, and body mass index. To assess predictive markers of incisional hernia risk, we screened the plasma proteome for >2,000 distinct proteins using a well-validated antibody microarray test. Paired t tests were used to compare protein levels between cases and controls. A gene-set-enrichment analysis (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) was applied to test for differences in signaling pathways between the 2 groups. Results The proteome screen identified 25 proteins that showed elevated or reduced plasma levels in the hernia group compared to the control group (nominal P values < .05). Several proteins were in pathways associated with wound healing (CCL21, SHBG, BRF2) or cell adhesion (PCDH15, CDH3, EPCAM). Conclusion Our study shows that there are multiple individual and groups of plasma proteins that could feasibly predict the personal hernia risk prior to undergoing an operation. Further investigations in larger, independent sample sets are warranted to replicate findings and validate clinical utility of potential biomarkers. After validation, such a biomarker could be incorporated into a multifactorial risk model to guide clinical decision-making.
Background Although the Ross operation requires double-valve replacement for aortic valve pathology, it is the only autologous, aortic valve replacement available. We report a single-unit's 11-year ...experience. Methods Before August 2006, 467 patients (mean age, 41 ± 15 years; 358 males) underwent a Ross operation. The right ventricular outflow tract was repaired with a cryopreserved pulmonary homograft. Follow-up was 94.4% complete. Results The 30-day mortality was 0.6%. The Kaplan-Meier survival estimate at 120 months was 94.4% ± 2.9% (standard error SE, 0.0146). Reoperation was due to autograft failure in 15 patients (7 repairs, 8 replacements), with a Kaplan-Meier freedom from autograft failure measured as reoperation or regurgitation exceeding grade II at 120 months of 94.2% ± 2.8% (SE, 0.0142). Homograft replacement, mostly due to stenosis, occurred in 11 patients. Freedom from homograft dysfunction, defined as homograft reoperation or peak homograft gradient of 30 mm Hg or more, at 120 months was 79.3% ± 7.3% (SE, 0.0372). Freedom from all autograft- and homograft-related reoperations at 120 months was 85.9% ± 6.3% (SE, 0.0321). Autograft or homograft endocarditis occurred in 8 patients, and 1 patient had simultaneous endocarditis of both valves. Conclusions Patient survival and freedom from prostheses-related events over 11 years still compares favorably with conventional heart valve prostheses. Mortality and morbidity remain low. Reoperation for autograft or homograft failure is higher than our previous reports, and endocarditis is also evident, 1.9% (9 of 467). Homograft dysfunction is higher in younger recipients.
Cachexia is a multifactorial syndrome that is characterized by loss of skeletal muscle mass in cancer patients. The biological pathways involved remain poorly characterized. Here, we compare urinary ...metabolic profiles in newly diagnosed colorectal cancer patients (stage I-IV) from the ColoCare Study in Heidelberg, Germany. Patients were classified as cachectic (
= 16), pre-cachectic (
= 13), or non-cachectic (
= 23) based on standard criteria on weight loss over time at two time points. Urine samples were collected pre-surgery, and 6 and 12 months thereafter. Fat and muscle mass area were assessed utilizing computed tomography scans at the time of surgery.
= 152 compounds were detected using untargeted metabolomics with gas chromatography-mass spectrometry and
= 154 features with proton nuclear magnetic resonance spectroscopy. Thirty-four metabolites were overlapping across platforms. We calculated differences across groups and performed discriminant and overrepresentation enrichment analysis. We observed a trend for 32 compounds that were nominally significantly different across groups, although not statistically significant after adjustment for multiple testing. Nineteen compounds could be identified, including acetone, hydroquinone, and glycine. Comparing cachectic to non-cachectic patients, higher levels of metabolites such as acetone (Fold change (FC) = 3.17;
= 0.02) and arginine (FC = 0.33;
= 0.04) were observed. The two top pathways identified were glycerol phosphate shuttle metabolism and glycine and serine metabolism pathways. Larger subsequent studies are needed to replicate and validate these results.
To determine associations between physical activity (PA), sedentary behavior (SB), and oxidative stress in colorectal cancer patients, ColoCare Study participants in Germany wore an accelerometer 6 ...and/or 12 months after surgery. Spearman partial correlations were used to assess associations between PA and urinary concentrations of oxidized guanine, a validated marker of oxidative stress. There were no significant associations between PA or SB and oxidized guanine in n = 76 measurements (ng/mg creatinine; r = 0.03, p = 0.76 for PA, r = –0.05, p = 0.69 for SB).
Novelty
Objectively measured PA was not associated with a marker of oxidative stress in colorectal cancer patients.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The separation of nitrogen and methane from hydrogen-rich mixtures is systematically investigated on a recently developed binder-free zeolite 5A. For this adsorbent, the present work provides a ...series of experimental data on adsorption isotherms and breakthrough curves of nitrogen and methane, as well as their mixtures in hydrogen. Isotherms were measured at temperatures of 283–313 K and pressures of up to 1.0 MPa. Breakthrough curves of CH4, N2, and CH4/N2 in H2 were obtained at temperatures of 300–305 K and pressures ranging from 0.1 to 6.05 MPa with different feed concentrations. An LDF-based model was developed to predict breakthrough curves using measured and calculated data as inputs. The number of parameters and the use of correlations were restricted to focus on the importance of measured values. For the given assumptions, the results show that the model predictions agree satisfactorily with the experiments under the different operating conditions applied.
Return of left ventricular mass to normal is considered to be a favorable result of aortic valve replacement. The Ross procedure provides near normal hemodynamics and thus allows studies of left ...ventricular (LV) reverse remodeling. LV mass regression may be influenced by surgical technique (subcoronary SC versus root replacement RR).
Data from the German Ross Registry were analyzed. A total of 646 patients (mean age: 43.6+/-12.7 years, range: 16 to 71 years; SC technique n=295, RR technique n=351) underwent a Ross procedure in 7 participating centers from 1990 to 2004. The patients underwent preoperative and postoperative echocardiographic evaluations. Mean follow-up time was 3.5+/-2.5 years (range 0.12 to 13.7 years). Follow-up completeness was 97%. The LV mass index (LVMI) decreased significantly during follow-up in both groups (SC: 209+/-53 preoperatively to 154+/-48 at 1-year follow-up, P<0.01 versus preoperative values to 149+/-51 g/m2 at 2-year follow-up, P=NS 1-year versus 2-year follow-up versus RR: from 195+/-56 preoperatively to 144+/-51 at 1-year follow-up P<0.01 versus preoperative values to 140+/-49 g/m2 P=NS 1-year versus 2-year follow-up). LVMI regression remained stagnant 1 year after the Ross procedure in most patients in both groups. On the basis of multivariate analysis, predictors for incomplete LVMI regression after the autograft procedure were high preoperative LVMI, smoking, and uncontrolled diastolic hypertension.
At mid-term echocardiographic follow-up, patients of both groups had favorable autograft hemodynamics. Risk factors for incomplete postoperative LVMI regression in our study were smoking and persistent diastolic hypertension. This emphasizes the importance of cessation of smoking and treatment of arterial hypertension, even in younger patients, after corrected aortic valve disease.
The Ross operation is increasingly accepted as an alternative to conventional valve prostheses for children, adolescents, and young adults. We review patients younger than 20 years of age.
Of 404 ...Ross operations done before November 2004, 60 were young patients with a median age of 12 years (range, 1 to 20 years). The pulmonary autograft technique universally was as a free root. A cryopreserved pulmonary homograft reconstructed the right ventricular outflow tract.
Early postoperative complications were reentry for bleeding in 2 patients and one pacemaker insertion. No thromboembolic or hemorrhagic events occurred during the follow-up of 42 ± 27 months. Two late deaths occurred, one from myocardial infarction after 3 months and another sudden death after 5 years, probably from critical pulmonary homograft stenosis. Echocardiographic follow-up revealed a median peak gradient of 6.3 ± 3 mm Hg across the autograft. The median pulmonary homograft peak gradient of 19.1 ± 13.7 mm Hg was increased to more than 30 mm Hg in 6 patients. Another 6 patients had moderate but clinically insignificant pulmonary homograft regurgitation. Altogether, 6 patients required reoperation for replacement of stenotic homografts. No autograft related reoperation occurred.
Young patients with the Ross operation had good mid-term autograft function and no perioperative mortality. Factors that justify the choice of the Ross operation for young patients are the normal physiologic hemodynamics and growth of the autograft as well as freedom from anticoagulation. A 10% reoperation rate, elevated pulmonary homograft gradients, and the surgical complexity remain limiting factors.
Objective To assess the association between achievement of prostate‐specific antigen (PSA) levels ≤0.2 ng/mL (henceforth ‘ultralow’) and clinical outcomes in patients in the ‘Targeted Investigational ...Treatment Analysis of Novel Anti‐androgen’ (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration‐sensitive prostate cancer (mCSPC). Patients and Methods Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide ( n = 525) or placebo ( n = 527) plus androgen‐deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2–>0.02 ng/mL (‘ultralow one’ UL1) and ≤0.02 ng/mL (‘ultralow two’ UL2) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression‐free survival (rPFS), overall survival (OS), time to castration‐resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan–Meier methods were used. Results By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide‐treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio HR 0.28, 95% confidence interval CI 0.14–0.54), OS (HR 0.24, 95% CI 0.13–0.43), TTCRPC (HR 0.2, 95% CI 0.11–0.38), and TTPP (HR 0.11, 95% CI 0.04–0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06–0.22; P < 0.001) in apalutamide‐treated patients. Conclusions In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. Patient Summary Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.
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