Dietmar Tamandl

Bio: Dietmar Tamandl is an academic researcher from Medical University of Vienna. The author has contributed to research in topics: Bevacizumab & Colorectal cancer. The author has an hindex of 30, co-authored 89 publications receiving 3525 citations. Previous affiliations of Dietmar Tamandl include University of Vienna & Iuliu Hațieganu University of Medicine and Pharmacy.

Vitamin D3 down-regulates monocyte TLR expression and triggers hyporesponsiveness to pathogen-associated molecular patterns.

Abstract: Toll-like receptors (TLR) represent an ancient front-line defence system that enables the host organism to sense the presence of microbial components within minutes As inducers of inflammation, TLR act as important triggers of distinct entities such as sepsis or autoimmune disease exacerbation We report here that vitamin D3 [1alpha,25-dihydroxycholecalciferol, 1,25(OH)(2)D3] suppresses the expression of TLR2 and TLR4 protein and mRNA in human monocytes in a time- and dose-dependent fashion Despite 1,25(OH)(2)D3-induced up-regulation of CD14, challenge of human monocytes with either LPS or lipoteichoic acid resulted in impaired TNF-alpha and procoagulatory tissue factor (CD142) production, emphasizing the critical role of TLR in the induction of inflammation Moreover, reduced TLR levels in 1,25(OH)(2)D3-treated phagocytes were accompanied by impaired NF-kappaB/RelA translocation to the nucleus and by reduced p38 and p42/44 (extracellular signal-regulated kinase 1/2) phosphorylation upon TLR-ligand engagement Both TLR down-regulation and CD14 up-regulation were substantially inhibited by the vitamin D receptor (VDR) antagonist ZK 159222, indicating that the immunomodulatory effect of 1,25(OH)(2)D3 on innate immunity receptors requires VDR transcription factor activation Our data provide strong evidence that 1,25(OH)(2)D3 primes monocytes to respond less effectively to bacterial cell wall components in a VDR-dependent mechanism, most likely due to decreased levels of TLR2 and TLR4

Bevacizumab, Capecitabine, and Oxaliplatin As Neoadjuvant Therapy for Patients With Potentially Curable Metastatic Colorectal Cancer

Abstract: Purpose Patients with colorectal cancer (CRC) and liver metastases have a poor prognosis, but can benefit from perioperative chemotherapy and disease resection. Bevacizumab improves outcomes in patients with metastatic CRC; however, its impact on surgical complications and hepatic regeneration after liver resection remains to be determined. Patients and Methods Fifty-six patients with metastatic CRC with liver metastases potentially curable by resection were eligible for this single-center, nonrandomized phase II trial. Eligibility criteria defined patients at high risk of early recurrence. Patients received biweekly bevacizumab plus capecitabine and oxaliplatin for six cycles. The sixth cycle of therapy did not include bevacizumab, resulting in 5 weeks between the last administration of bevacizumab and surgery. Results Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%). Fifty-two patients underwent liver resection including 11 with synchronous primary tumor resection. No inc...

Cetuximab, gemcitabine, and oxaliplatin in patients with unresectable advanced or metastatic biliary tract cancer: a phase 2 study

Abstract: Summary Background Patients with biliary tract cancer have a poor prognosis, and, until recently, no standard palliative chemotherapy has been defined We aimed to investigate the efficacy and safety of cetuximab in combination with gemcitabine and oxaliplatin (GEMOX) for first-line treatment of biliary tract cancer Methods From Oct 1, 2006, to July 26, 2008, patients with unresectable locally advanced or metastatic biliary tract cancer were sequentially enrolled and treated at one centre in Austria All patients received intravenous infusions of 500 mg/m 2 cetuximab on day 1, 1000 mg/m 2 gemcitabine on day 1, and 100 mg/m 2 oxaliplatin on day 2, every 2 weeks for 12 cycles The primary outcome was overall response rate Analysis was by intention to treat Adverse reactions were assessed according to National Cancer Institute Common Toxicity Criteria The study is completed and registered with ClinicalTrialsgov, number NCT01216345 Findings 30 patients with median age of 68 years (IQR 62–73) were enrolled and included in the analysis Objective response occurred in 19 patients (63%; 95% CI 56·2–69·8), of whom three (10%; 3·2–16·8) achieved complete response, and 16 (53%; 46·2–59·8) achieved partial response Nine patients underwent potentially curative secondary resection after major response to therapy Grade 3 adverse events were recorded in 13 patients: skin rash (n=4), peripheral neuropathy (n=4), thrombocytopenia (n=3), nausea (n=1), diarrhoea (n=1), and neutropenia (n=1); no grade 4 adverse events were recorded Interpretation Cetuximab plus GEMOX was well tolerated and had encouraging antitumour activity, leading to secondary resection in a third of patients These findings warrant further study of cetuximab plus GEMOX in a large randomised trial Funding Association of Research on the Biology of Liver Tumors, Vienna, Austria

Markers of sarcopenia quantified by computed tomography predict adverse long-term outcome in patients with resected oesophageal or gastro-oesophageal junction cancer

Abstract: To assess the impact of sarcopenia and alterations in body composition parameters (BCPs) on survival after surgery for oesophageal and gastro-oesophageal junction cancer (OC). 200 consecutive patients who underwent resection for OC between 2006 and 2013 were selected. Preoperative CTs were used to assess markers of sarcopenia and body composition (total muscle area [TMA], fat-free mass index [FFMi], fat mass index [FMi], subcutaneous, visceral and retrorenal fat [RRF], muscle attenuation). Cox regression was used to assess the primary outcome parameter of overall survival (OS) after surgery. 130 patients (65 %) had sarcopenia based on preoperative CT examinations. Sarcopenic patients showed impaired survival compared to non-sarcopenic individuals (hazard ratio [HR] 1.87, 95 % confidence interval [CI] 1.15–3.03, p = 0.011). Furthermore, low skeletal muscle attenuation (HR 1.91, 95 % CI 1.12–3.28, p = 0.019) and increased FMi (HR 3.47, 95 % CI 1.27–9.50, p = 0.016) were associated with impaired outcome. In the multivariate analysis, including a composite score (CSS) of those three parameters and clinical variables, only CSS, T-stage and surgical resection margin remained significant predictors of OS. Patients who show signs of sarcopenia and alterations in BCPs on preoperative CT images have impaired long-term outcome after surgery for OC. • Sarcopenia is associated with impaired OS after surgery for oesophageal cancer. • Other body composition parameters are also associated with impaired survival. • This influence on survival is independent of established clinical parameters. • Sarcopenia provides a better estimation of cachexia than BMI. • Sarcopenia assessment could be considered in risk/benefit stratification before oesophagectomy.

Monocyte toll-like receptor 4 expression and LPS-induced cytokine production increase during gestational aging.

Abstract: Premature newborns are highly susceptible to severe bacterial infections. This is partially due to their immature innate immune system, characterized by decreased neutrophil and monocyte activity as well as by reduced concentrations of complement factors. However, additional mechanisms might be important for innate immunity and are still the subject of considerable debate. The importance of pattern recognition domains such as Toll-like receptors (TLR) has been fully acknowledged within the last few years. Therefore, we investigated age-related monocyte TLR4 expression and lipopolysaccharide-induced cytokine secretion from very low birth weight infants (VLBWI) and from newborns after wk 30 of gestation in comparison to healthy adults. In VLBWI, expression of TLR4 surface protein, detected by flow cytometry, and TLR4-specific mRNA, quantified by real time-PCR, were significantly reduced in comparison to mature infants and to adults. Reduced TLR4 expression was paralleled by significantly diminished ex vivo LPS stimulated IL-1beta, IL-6, and tumor necrosis factor-alpha secretion into whole blood. We conclude that, in VLBWI, the minimized expression of TLR4 contributes to the susceptibility of VLBWI to infections with Gram-negative bacteria due to the lack of cytokines to boost initial immune response.

Nonalcoholic Fatty Liver Disease: A Systematic Review

Abstract: Importance Nonalcoholic fatty liver disease and its subtype nonalcoholic steatohepatitis affect approximately 30% and 5%, respectively, of the US population. In patients with nonalcoholic steatohepatitis, half of deaths are due to cardiovascular disease and malignancy, yet awareness of this remains low. Cirrhosis, the third leading cause of death in patients with nonalcoholic fatty liver disease, is predicted to become the most common indication for liver transplantation. Objectives To illustrate how to identify patients with nonalcoholic fatty liver disease at greatest risk of nonalcoholic steatohepatitis and cirrhosis; to discuss the role and limitations of current diagnostics and liver biopsy to diagnose nonalcoholic steatohepatitis; and to provide an outline for the management of patients across the spectrum of nonalcoholic fatty liver disease. Evidence Review PubMed was queried for published articles through February 28, 2015, using the search termsNAFLD and cirrhosis, mortality, biomarkers,andtreatment. A total of 88 references were selected, including 14 randomized clinical trials, 19 cohort or case-control studies, 1 population-based study, 2 practice guidelines, 7 meta-analyses, 43 classified as other, and 2 webpages. Findings Sixty-six percent of patients older than 50 years with diabetes or obesity are thought to have nonalcoholic steatohepatitis with advanced fibrosis. Even though the ability to identify the nonalcoholic steatohepatitis subtype within those with nonalcoholic fatty liver disease still requires liver biopsy, biomarkers to detect advanced fibrosis are increasingly reliable. Lifestyle modification is the foundation of treatment for patients with nonalcoholic steatosis. Available treatments with proven benefit include vitamin E, pioglitazone, and obeticholic acid; however, the effect size is modest ( Conclusions and Relevance Between 75 million and 100 million individuals in the United States are estimated to have nonalcoholic fatty liver disease and its potential morbidity extends beyond the liver. It is important that primary care physicians, endocrinologists, and other specialists be aware of the scope and long-term effects of the disease. Early identification of patients with nonalcoholic steatohepatitis may help improve patient outcomes through treatment intervention, including transplantation for those with decompensated cirrhosis.

Clinical practice guidelines in oncology

Abstract: Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions in the breast ducts. The goal for management of DCIS is to prevent the development of invasive breast cancer. This manuscript focuses on the NCCN Guidelines Panel recommendations for the workup, primary treatment, risk reduction strategies, and surveillance specific to DCIS.

Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

Abstract: The vitamin D endocrine system is essential for calcium and bone homeostasis. The precise mode of action and the full spectrum of activities of the vitamin D hormone, 1,25-dihydroxyvitamin D [1,25-(OH)2D], can now be better evaluated by critical analysis of mice with engineered deletion of the vitamin D receptor (VDR). Absence of a functional VDR or the key activating enzyme, 25-OHD-1α-hydroxylase (CYP27B1), in mice creates a bone and growth plate phenotype that mimics humans with the same congenital disease or severe vitamin D deficiency. The intestine is the key target for the VDR because high calcium intake, or selective VDR rescue in the intestine, restores a normal bone and growth plate phenotype. The VDR is nearly ubiquitously expressed, and almost all cells respond to 1,25-(OH)2D exposure; about 3% of the mouse or human genome is regulated, directly and/or indirectly, by the vitamin D endocrine system, suggesting a more widespread function. VDR-deficient mice, but not vitamin D- or 1α-hydroxylase-deficient mice, and man develop total alopecia, indicating that the function of the VDR and its ligand is not fully overlapping. The immune system of VDR- or vitamin D-deficient mice is grossly normal but shows increased sensitivity to autoimmune diseases such as inflammatory bowel disease or type 1 diabetes after exposure to predisposing factors. VDR-deficient mice do not have a spontaneous increase in cancer but are more prone to oncogene- or chemocarcinogen-induced tumors. They also develop high renin hypertension, cardiac hypertrophy, and increased thrombogenicity. Vitamin D deficiency in humans is associated with increased prevalence of diseases, as predicted by the VDR null phenotype. Prospective vitamin D supplementation studies with multiple noncalcemic endpoints are needed to define the benefits of an optimal vitamin D status.