AIMS Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. METHODS AND RESULTS Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. CONCLUSION Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship.

For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibit angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.

Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia. The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF. A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured. Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A–antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia. Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia.

BACKGROUND Blood flow in the intestinal arteries is reduced in patients with stable heart failure (HF) and relates to gastrointestinal (GI) symptoms and cardiac cachexia.OBJECTIVES The aims of this study were to measure arterial intestinal blood flow and assess its role in juxtamucosal bacterial growth, GI symptoms, and cachexia in patients with HF.METHODS A total of 65 patients and 25 controls were investigated. Twelve patients were cachectic. Intestinal blood flow and bowel wall thickness were measured using ultrasound. GI symptoms were documented. Bacteria in stool and juxtamucosal bacteria on biopsies taken during sigmoidoscopy were studied in a subgroup by fluorescence in situ hybridization. Serum lipopolysaccharide antibodies were measured.RESULTS Patients showed 30% to 43% reduced mean systolic blood flow in the superior and inferior mesenteric arteries and celiac trunk (CT) compared with controls (p < 0.007 for all). Cachectic patients had the lowest blood flow (p < 0.002). Lower blood flow in the superior mesenteric artery and CT was correlated with HF severity (p < 0.04 for all). Patients had more feelings of repletion, flatulence, intestinal murmurs, and burping (p < 0.04). Burping and nausea or vomiting were most severe in patients with cachexia (p < 0.05). Patients with lower CT blood flow had more abdominal discomfort and immunoglobulin A-antilipopolysaccharide (r = 0.76, p < 0.02). Antilipopolysaccharide response was correlated with increased growth of juxtamucosal but not stool bacteria. Patients with intestinal murmurs had greater bowel wall thickness of the sigmoid and descending colon, suggestive of edema contributing to GI symptoms (p < 0.05). In multivariate regression analysis, lower blood flow in the superior mesenteric artery, CT (p < 0.04), and inferior mesenteric artery (p = 0.056) was correlated with the presence of cardiac cachexia.CONCLUSIONS Intestinal blood flow is reduced in patients with HF. This may contribute to juxtamucosal bacterial growth and GI symptoms in patients with advanced HF complicated by cachexia. (c) 2014 by the American College of Cardiology Foundation.

Ge ZZ, Chen HM, Gao YJ, Liu WZ, Xu CH, Tan HH, Chen HY, Wei W, Fang JY, Xiao SD. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology 2011; 141: 1629–1637 Lazzerini M, Martelossi S, Magazzù G, Pellegrino S, Lucanto MC, Barabino A, Calvi A, Arrigo S, Lionetti P, Lorusso M, Mangiantini F, Fontana M, Zuin G, Palla G, Maggiore G, Bramuzzo M, Pellegrin MC, Maschio M, Villanacci V, Manenti S, Decorti G, De Iudicibus S, Paparazzo R, Montico M, Ventura A. Effect of Thalidomide on Clinical Remission in Children and Adolescents with Refractory Crohn Disease – A Randomized Clinical Trial. JAMA 2013; 310: 2164– 2173

Gillams AR, Lees WR. Five-year survival in 309 patients with colorectal liver metastases treated with radiofrequency ablation. Eur Radiol 2009; 19: 1206 – 1213.

Hintergrund: Die Radiofrequenzablation (RFA) stellt ein etabliertes Therapieverfahren zur Behandlung des Hepatozellulären Karzinoms (HCC) dar. Der Erfolg der Therapie ist jedoch von Faktoren wie Größe und Lokalisation abhängig. Die Mehrzahl der HCC sind nodulär konfiguriert und gut abgrenzbar, jedoch sind bereits sehr kleine HCC <3 cm teilweise durch ein frühinfiltratives Wachstum mit unscharfen Randbegrenzungen gekennzeichnet. Ziel: Ziel der Studie war es, zu untersuchen, ob infiltrative HCC schlechtere Ergebnisse nach RFA als nodulär konfigurierte HCC zeigen. Methoden: 28 Pat. mit insgesamt 34 histologisch gesicherten HCC < 5 cm (mittl. Größe: 28,1±1,4mm) wurden mittels US und Kontrastsonografie (CEUS; SonoVue 2ml; Bracco; Siemens Acuson Sequoia, CPS) untersucht, hinsichtlich des Wachstumstyps in nodulär bzw. infiltrativ klassifiziert und mittels RFA behandelt. Ergebnisse: 24/34 (71%) der HCC waren nodulär konfiguriert und gut abgrenzbar, 10/34 (29%) infiltrativ. Die Gruppen unterschieden sich nicht hinsichtlich Tumorgröße (29,4 vs. 23,7mm), Häufigkeit subkapsulärer Lokalisation und Nähe zu großen Gefäßen. Insgesamt traten während einer mittleren Verlaufsbeobachtung von 23 Monaten bei 7/34 (19%) aller abladierten HCC Lokalrezidive auf. Bei nodulären HCC traten in 2/24 (8%) Fällen Lokalrezidive auf, bei infiltrativen HCC hingegen in 5/10 (50%) Fällen (p<0,01). Bei frühinfiltrativen HCC mit unscharfen Tumorrändern waren die Ablationsvolumina kleiner und mehr RFA-Prozeduren erforderlich (p<0,03). Zusammenfassung: Frühinfiltrative, sonographisch unscharf abgrenzbare HCC zeigen ungünstigere Ablationsergebnisse nach RFA. Für diese Tumore sollten modifizierte RFA-Protokolle evaluiert werden.

Aim: Radiofrequency thermal ablation (RFA) has shown promise as a technique for treating solid tumors. This method has been suggested as an alternative to surgery in patients with adrenocortical carcinoma (ACC).Materials and Methods: We reviewed the literature, and report the case of a patient with stage 4 ACC who received intraoperative and percutaneous RFA of two liver metastasis according to a standard ablation protocol.Results: Post-interventional imaging in our patient demonstrated that after both interventions, a stellar-like structure of vital tumor tissue had remained within the coagulation necrosis. This was the starting point of a fast and progressive tumor recurrence. We suspect heat-sink effects of blood vessels in the highly vascularized metastasis to cause the tumor recurrence. In literature, there are only a few reports of RFA in ACC patients. In addition, there is no large randomized trial investigating the efficacy of RFA against surgery in those patients.Conclusions: Presently, RFA in ACC should be restricted to patients in whom surgery is contraindicated. It is necessary that strongly vascularized ACC metastases deserve a modified ablation protocol due to perfusion related cooling effects and to increase the efficacy of RFA.

Nonalcoholic fatty liver disease represents the hepatic manifestation of the metabolic syndrome. Nonalcoholic steatohepatitis (NASH) is the progressive form of liver injury. The pathophysiology that leads to NASH is not well understood.We hypothesize that an altered cortisol metabolism in the liver may be a pathogenetic factor.75 patients (28 men, 47 women) underwent liver biopsy for elevation in liver enzymes. Histological diagnosis identified normal liver in eight, fatty liver in 20, NASH grade 1 in 22, grade 2 in nine, grade 3 in three patients, and other forms of hepatitis or cirrhosis in 13 patients. We quantified hepatic 11beta-hydroxysteroid dehydrogenase type1 (11beta-HSD1) and hexose-6-phosphate-dehydrogenase (H6PDH) mRNA expression by real-time PCR. In addition, analysis of 24 h urinary excretion of cortisol metabolites using GCMS was performed and compared with healthy controls.11beta-HSD1 mRNA expression correlated significantly (R2= 0.809; P < 0.001) with H6PDH mRNA expression, negatively with waist-to-hip ratio in women (R2= 0.394; P= 0.005), but not with urinary (THF + 5alpha-THF)/THE ratio, total cortisol metabolite excretion, age, BMI, degree of fatty liver or NASH stages. Total cortisol metabolite excretion was increased in patients with fatty liver or NASH compared with healthy controls.Our data suggest that expression of hepatic 11beta-HSD1 and H6PDH are closely interlinked. 11beta-HSD1 gene expression does not seem to be involved in the pathogenesis of fatty liver or NASH. However, those patients showed an increased 5alpha- and 5beta-reduction of cortisol leading to an increased cortisol turnover rate and an activation of the HPA axis.

Hintergrund: Perkutane Ethanolinjektion (PEI) und Radiofrequenzablation (RFA) stellen etablierte Therapieverfahren zur Behandlung des Hepatozellulären Karzinoms (HCC) dar. Der Erfolg der Therapie ist jedoch von Faktoren wie Größe und Lokalisation abhängig. Die Mehrzahl der HCC sind nodulär konfiguriert und gut abgrenzbar, jedoch sind bereits sehr kleine HCC <3–5cm teilweise durch ein frühinfiltratives Wachstum mit unscharfen Randbegrenzungen gekennzeichnet.

Problemstellung: Perkutane Ethanolinjektion (PEI) und Radiofrequenzablation (RFA) stellen etablierte Therapieverfahren zur Behandlung des hepatozellulären Karzinoms (HCC) bzw. maligner Lebertumore dar. Die Überwachung nach Therapie erfolgt üblicherweise mittels Computertomografie (CT). Die Kontrastsonografie (CEUS) stellt ein geeignetes Verfahren zur Therapiekontrolle dar. Wir verglichen CEUS und CT zur Überwachung von Patienten nach ablativer Therapie von Lebertumoren.