Early Detection of a Colorectal Carcinoma in an Asymptomatic Patient Using a Combined DNA Stool Test.

BACKGROUND: Modern, simple stool tests could close the gap regarding the recognition rate (sensitivity) between the current test methods and colonoscopy. METHODS: Here we report a case of a 68-year-old asymptomatic patient, who applied an innovative combined DNA stool test. RESULTS: Due to a positive KRAS mutation, a colonoscopy was performed and an invasive adenocarcinoma was diagnosed. After colonoscopical resection in two steps pathological findings could not be identified anymore. All further parameters, including KRAS, stayed continuously negative. CONCLUSIONS: In this case report, it was demonstrated that a combined DNA stool test can also be successfully applied as alternative diagnostic tool.

Intra- and Inter-rater Reliability of Navigated Ultrasound in the Assessment of Pelvic Tilt in Symptom-Free Young Adults.

OBJECTIVES: Pelvic tilt is the angle between the anterior pelvic plane and the coronal plane. It affects cup positioning in total hip arthroplasty. The primary objective of this study was to test the intra- and inter-rater reliability of a navigated smart device-based ultrasound system for pelvic tilt assessment. The secondary objective was to test the inter-rater variability of the measurements on a hip phantom. METHODS: A repeated-measures design was used. Two raters measured the pelvic tilt of 12 symptom-free young adults in upright and supine positions. Additionally, pelvic tilt was measured on a hip phantom. Each rater performed 3 measurements in each body position on the participants and 12 measurements on the hip phantom. Intra- and inter-rater reliability were calculated with the use of intraclass correlation coefficients. The variability in measurements on the hip phantom was assessed by a Bland-Altman analysis of agreement. RESULTS: Intraclass correlation coefficient 95% confidence intervals for intra-rater reliability ranged from good to excellent and moderate to excellent for the supine and upright positions respectively. Intraclass correlation coefficient 95% confidence intervals for inter-rater reliability ranged from poor to excellent for both positions. Hip phantom measurements showed no significant average bias (P > .05) and no significant proportional bias (P > .05). The 95% inter-rater limits of agreement were ±1.3° and ±1.7° for the supine and upright positions, respectively. CONCLUSIONS: The intra-rater reliability values achieved were suitable. Intraclass correlation coefficient values for inter-rater reliability remained below an acceptable level. Possible reasons and overcoming strategies were presented. The 95% limits of agreement were good, at less than ±2°.

[Mid-term, relatively tumor-stable outcome after an initially successful interdisciplinary surgical intervention with locally achieved R0 resection status including a multimodal therapeutic concept of a metastasized leiomyosarcoma of the inferior vena cava]. / Mittelfristiges, relativ tumorstabiles Outcome eines erfolgreich interdisziplinär lokal R0-resezierten, metastasierten Leiomyosarkoms der V. cava inferior mit multimodaler Behandlung.

UNLABELLED: Progredient tumor-growth does not mean necessarily nihilism since (because of the latest multimodal therapeutic options) it might be possible to convert the malignant disease into a chronic stage depending on tumor entity, specific tumor-associated findings and expertise of the interdisciplinary oncological/oncosurgical team to utilize available and potential therapeutic measures. The aim of this report on an unusual case (with its patient-associated, therapeutic and prognostic aspects) of a leiomyosarcoma of the inferior vena cava with advanced tumor growth (characterized initially by pulmonary and hepatic, later on by additional vertebral metastases) is to illustrate its changeful clinical course after and during multimodal treatment episodes comprising surgical (abdomino-/vascular-/cardio- and neurosurgical-locally, R0 resection status), radiological and chemotherapeutic measures. A relatively stable disease over a specific time period of 5 years and 6 months was achieved. The 54-year old female patient with metastasized leiomyosarcoma of the inferior vena cava underwent local tumor resection en bloc with inferior vena cava segmental resection (following vascular surgical interposition of a prosthesis) and hemihepatectomy as well as resection of hepatic segment I. After recovery, a multistep and -modal treatment was initiated comprising of various protocols of systemic chemotherapy, thermoablation of recurrent hepatic metastases, various brachytherapy procedures (for hepatic and pulmonary metastases) and resection of a cerebral metastasis by a neurosurgeon including subsequent radiation. CONCLUSIONS: The patient demonstrates impressively that even in case of advanced tumor stage with initial, novel and recurrent metastases, a relatively stable disease over an intermediate time period (of more than 5 years) with an acceptable quality of life was achieved despite several complications.

Transcriptome analysis of the spalax hypoxia survival response includes suppression of apoptosis and tight control of angiogenesis.

BACKGROUND: The development of complex responses to hypoxia has played a key role in the evolution of mammals, as inadequate response to this condition is frequently associated with cardiovascular diseases, developmental disorders, and cancers. Though numerous studies have used mice and rats in order to explore mechanisms that contribute to hypoxia tolerance, these studies are limited due to the high sensitivity of most rodents to severe hypoxia. The blind subterranean mole rat Spalax is a hypoxia tolerant rodent, which exhibits unique longevity and therefore has invaluable potential in hypoxia and cancer research. RESULTS: Using microarrays, transcript abundance was measured in brain and muscle tissues from Spalax and rat individuals exposed to acute and chronic hypoxia for varying durations. We found that Spalax global gene expression response to hypoxia differs from that of rat and is characterized by the activation of functional groups of genes that have not been strongly associated with the response to hypoxia in hypoxia sensitive mammals. Using functional enrichment analysis of Spalax hypoxia induced genes we found highly significant overrepresentation of groups of genes involved in anti apoptosis, cancer, embryonic/sexual development, epidermal growth factor receptor binding, coordinated suppression and activation of distinct groups of transcription factors and membrane receptors, in addition to angiogenic related processes. We also detected hypoxia induced increases of different critical Spalax hub gene transcripts, including antiangiogenic genes associated with cancer tolerance in Down syndrome human individuals. CONCLUSIONS: This is the most comprehensive study of Spalax large scale gene expression response to hypoxia to date, and the first to use custom Spalax microarrays. Our work presents novel patterns that may underlie mechanisms with critical importance to the evolution of hypoxia tolerance, with special relevance to medical research.

Risk of wound hematoma at carotid endarterectomy under dual antiplatelet therapy.

BACKGROUND AND PURPOSE: This study aims to assess perioperative incidence of wound hematoma and bleeding in patients who underwent carotid endarterectomy (CEA) under dual antiplatelet therapy. METHODS: Consecutive patients with initial CEA receiving aspirin, clopidogrel, or a combination of both were subjected to standard patch endarterectomy. Postoperative wound hematoma was assessed as moderate (subcutaneous bleeding, nonspace-occupying hematoma, and oozing suture bleeding) or severe, i.e., needing operative re-exploration. RESULTS: Six hundred eighty-four (80.9%) patients with one of the three types of antiplatelet therapy out of 844 patients registered from 1995 to 2010 were enrolled. Wound hematoma occurred in 27 of 112 (24.1%) patients under combined aspirin and clopidogrel, 33 of 162 (20.4%) under clopidogrel, and 48 of 410 (11.7 %) under aspirin. Relative risk compared to aspirin was 2.4 (95% CI, 1.4 to 4.1) for aspirin and clopidogrel and 1.9 (95% CI, 1.2 to 3.1) for clopidogrel. Severe space-occupying hematoma needing operative re-exploration occurred in four (3.6%) patients under aspirin and clopidogrel, seven (4.3%) under clopidogrel, and five (1.2%) under aspirin. Corresponding relative risks were 3.0 (95% CI, 0.8 to 11.4) for aspirin and clopidogrel and 3.7 (95% CI, 1.1 to 11.7) for clopidogrel. Relative risks remained without relevant change after adjustment for potentially confounding variables. CONCLUSIONS: Dual antiplatelet therapy with combined aspirin and clopidogrel as well as clopidogrel is associated with an increased incidence of perioperative wound hematoma compared to aspirin but on an acceptable low level of incidence. The latter may be achieved by adapting operative procedures to more intensive antiplatelet regimes.

The crude latex of Euphorbia tirucalli modulates the cytokine response of leukocytes, especially CD4+ T lymphocytes

The plants of the Euphorbiaceae family, especially those of the genus Euphorbia, are frequently used by Brazilian folk communities to treat a wide variety of infectious, tumoral and inflammatory illnesses. Among the species of this genus, Euphorbia tirucalli L. is widely used in some Brazilian regions, such as the Jequitinhonha River Valley. There is evidence that the latex produced by E. tirucalli has antiviral and antitumor activities, but little is known about the mechanisms involved in these effects. It is likely that the mechanism for such activities involves leukocyte activation and cytokine production. In this work, we aimed to evaluate the production of type 1 (TNF-α and IFN-γ) and type 2 (IL-4 and IL-10) cytokines by circulating leukocyte subsets submitted to brief stimulation with the crude latex of E. tirucalli. Peripheral blood leukocytes of twenty healthy subjects were submitted to 4 h incubation with crude E. tirucalli latex diluted in dimethylsulfoxide. After the incubation period, the cells were stained with FITC-conjugated monoclonal antibodies specific to the cell surface receptors CD4, CD8 and CD14, and to PE-conjugated monoclonal antibodies specific to the cytokines TNF-α, IFN-γ, IL-4 and IL-10. The acquisition and analysis of data were performed by flow cytometry. The results showed a significant increase (p<0.05) in the percentage of CD4+ T lymphocytes positive for the type 1 cytokines TNF-α and IFN-γ. Neutrophils and CD8+ T lymphocytes showed a mixed profile of cytokine production, characterized by an increase in the percentage of cells expressing IFN-γ, TNF-α, and IL-10. The data indicate a predominant type 1 cytokine response. The findings presented suggest that the effect popularly attributed to E. tirucalli usage may be attributed to its effect on the production of TNF-α and IFN-γ. However, the relationship between the in vitro and in vivo effects of E. tirucalli needs to be investigated.

Sympathetic modulation of intestinal microvascular blood flow oscillations in experimental endotoxemia.

Impairment of the intestinal microcirculation has been recognized as an important factor in the pathogenesis of endotoxin related sepsis syndrome. We investigated the effects of endotoxemia on the variability of intestinal microvascular blood flow (IMBF) and arterial blood pressure (BP) in a prospective, randomized, controlled animal study. Recordings of IMBF (laser Doppler fluxmetry) and BP were performed before, two and four hours after i.v. injection of either placebo or endotoxin (5 mg/kg b.w. lipopolysaccharide from E. coli, serotype O55:B5). Control experiments were performed with systemic (clonidine) and local intestinal (surgery) sympathectomy. Spectral analysis was performed using the autoregressive approach. Spectral power was determined in two frequency bands (low frequency (LF): 0.27-0.74 Hz; high frequency (HF): 0.76-3.00 Hz). Two hours after endotoxin challenge a significant decrease in IMBF was observed. LF spectral power of IMBF and BP increased significantly in the endotoxin challenged group, while no effects were observed in the placebo group. Four hours after endotoxin administration IMBF decreased further and LF spectral power of IMBF and BP remained elevated. Denervation prevented the decrease in IMBF but did not abolish the LF power increase. Clonidine administration attenuated the IMBF decrease and significantly diminished the increase in LF spectral power of IMBF and BP. We conclude that endotoxemia is associated with increased sympathetic outflow to the systemic vasculature, as indicated by the increase in LF spectral power of arterial blood pressure. The increase in LF variability of IMBF is secondary to the increase in LF spectral power of BP, since it could be attenuated by systemic and not by local intestinal sympathectomy.