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Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra‐operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low‐risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1–2), estrogen receptor‐positive and human‐epidermal‐growth‐factor‐receptor‐2‐negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow‐up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50–86) years at diagnosis. Median follow‐up was 60 (8–120) months. Five‐year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4–17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer‐related death was observed. Estimated 5‐year overall survival was 89.8% (95% CI 86.0–93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR. [ABSTRACT FROM AUTHOR]

The article presents the discussion on worldwide pandemic of type 2 diabetes (T2D) and obesity. Topics include duodenal-jejunal bypass liner being developed to mimic the proposed small-bowel mechanisms of Roux-en-Y gastric bypass; and decrease in medication dosages and/or discontinuation of antidiabetes medication such as insulin being a recognized benefit of EndoBarrier treatment .

Investigate the safety and efficacy of 6 months' duodenal-jejunal bypass liner (DJBL) treatment in comparison with dietary intervention for obesity and type 2 diabetes mellitus (T2DM).The DJBL is a bariatric procedure involving an impermeable sleeve that is delivered endoscopically in the proximal intestine. This procedure not only is less invasive than conventional surgical techniques but also has beneficial effects on obesity and T2DM.A multicenter randomized controlled trial was conducted. Seventy-seven patients with obesity and T2DM were included. Thirty-eight patients were randomized to 6 months' DJBL treatment in combination with dietary intervention (34 successfully implanted, 31 completed the study), 39 patients received only dietary intervention (controls, 35 completed the study). Total study duration for both groups was 12 months, including 6 months of post-DJBL removal follow-up.After 6 months, just before DJBL removal, the DJBL group had lost 32.0% [22.0%-46.7%] of their excess weight versus 16.4% [4.1%-34.6%] in the control group (P < 0.05). Glycated hemoglobin A1c levels improved to 7.0% [6.4%-7.5%] in the DJBL group and to 7.9% [6.6%-8.3%] in the control group (P < 0.05). In addition, 85.3% of DJBL patients showed decreased postprandial glucose excursions versus 48.7% of control patients (P < 0.05). At 12 months, excess weight loss of the DJBL group was 19.8% [10.6%-45.0%] versus 11.7% [1.4%-25.4%] in the control group (P < 0.05). HbA1c was 7.3% [6.6%-8.0%] versus 8.0% [6.8%-8.8%], DJBL versus control respectively (P = ns).The DJBL is a safe and effective alternative to invasive bariatric procedures. Six months of DJBL treatment combined with diet leads to superior weight loss and improvement of T2DM when compared with diet alone. [ABSTRACT FROM AUTHOR]

The innate immune system plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH). Recently we reported complement activation in human NASH. However, it remained unclear whether the alternative pathway of complement, which amplifies C3 activation and which is frequently associated with pathological complement activation leading to disease, was involved. Here, alternative pathway components were investigated in liver biopsies of obese subjects with healthy livers (n = 10) or with NASH (n = 12) using quantitative PCR, Western blotting, and immunofluorescence staining. Properdin accumulated in areas where neutrophils surrounded steatotic hepatocytes, and colocalized with the C3 activation product C3c. C3 activation status as expressed by the C3c/native C3 ratio was 2.6-fold higher (p<0.01) in subjects with NASH despite reduced native C3 concentrations (0.94±0.12 vs. 0.57±0.09; p<0.01). Hepatic properdin levels positively correlated with levels of C3c (rs = 0.69; p<0.05) and C3c/C3 activation ratio (rs = 0.59; p<0.05). C3c, C3 activation status (C3c/C3 ratio) and properdin levels increased with higher lobular inflammation scores as determined according to the Kleiner classification (C3c: p<0.01, C3c/C3 ratio: p<0.05, properdin: p<0.05). Hepatic mRNA expression of factor B and factor D did not differ between subjects with healthy livers and subjects with NASH (factor B: 1.00±0.19 vs. 0.71±0.07, p = 0.26; factor D: 1.00±0.21 vs. 0.66±0.14, p = 0.29;). Hepatic mRNA and protein levels of Decay Accelerating Factor tended to be increased in subjects with NASH (mRNA: 1.00±0.14 vs. 2.37±0.72; p = 0.22; protein: 0.51±0.11 vs. 1.97±0.67; p = 0.28). In contrast, factor H mRNA was downregulated in patients with NASH (1.00±0.09 vs. 0.71±0.06; p<0.05) and a similar trend was observed with hepatic protein levels (1.12±0.16 vs. 0.78±0.07; p = 0.08). Collectively, these data suggest a role for alternative pathway activation in driving hepatic inflammation in NASH. Therefore, alternative pathway factors may be considered attractive targets for treating NASH by inhibiting complement activation. [ABSTRACT FROM AUTHOR]

Objective Intestinal microbiota have been suggested to contribute to the development of obesity, but the mechanism remains elusive. The relationship between microbiota composition, intestinal permeability, and inflammation in nonobese and obese subjects was investigated. Design and Methods Fecal microbiota composition of 28 subjects (BMI 18.6-60.3 kg m−2) was analyzed by a phylogenetic profiling microarray. Fecal calprotectin and plasma C-reactive protein levels were determined to evaluate intestinal and systemic inflammation. Furthermore, HbA1c, and plasma levels of transaminases and lipids were analyzed. Gastroduodenal, small intestinal, and colonic permeability were assessed by a multisaccharide test. Results Based on microbiota composition, the study population segregated into two clusters with predominantly obese (15/19) or exclusively nonobese (9/9) subjects. Whereas intestinal permeability did not differ between clusters, the obese cluster showed reduced bacterial diversity, a decreased Bacteroidetes/Firmicutes ratio, and an increased abundance of potential proinflammatory Proteobacteria. Interestingly, fecal calprotectin was only detectable in subjects within the obese microbiota cluster ( n = 8/19, P = 0.02). Plasma C-reactive protein was also increased in these subjects ( P = 0.0005), and correlated with the Bacteroidetes/Firmicutes ratio ( rs = −0.41, P = 0.03). Conclusions Intestinal microbiota alterations in obese subjects are associated with local and systemic inflammation, suggesting that the obesity-related microbiota composition has a proinflammatory effect. [ABSTRACT FROM AUTHOR]

Background & Aims: Histological evaluation of a liver biopsy is the current gold standard to diagnose non-alcoholic steatohepatitis (NASH), but the procedure to obtain biopsies is associated with morbidity and high costs. Hence, only subjects at high risk are biopsied, leading to underestimation of NASH prevalence, and undertreatment. Since analysis of volatile organic compounds in breath has been shown to accurately identify subjects with other chronic inflammatory diseases, we investigated its potential as a non-invasive tool to diagnose NASH., Methods: Wedge-shaped liver biopsies from 65 subjects (BMI 24.8-64.3 kg/m(2)) were obtained during surgery and histologically evaluated. The profile of volatile organic compounds in pre-operative breath samples was analyzed by gas chromatography-mass spectrometry and related to liver histology scores and plasma parameters of alanine aminotransferase (ALT) and aspartate aminotransferase (AST)., Results: Three exhaled compounds were sufficient to distinguish subjects with (n=39) and without NASH (n=26), with an area under the ROC curve of 0.77. The negative and positive predictive values were 82% and 81%. In contrast, elevated ALT levels or increased AST/ALT ratios both showed negative predictive values of 43%, and positive predictive values of 88% and 70%, respectively. The breath test reduced the hypothetical percentage of undiagnosed NASH patients from 67-79% to 10%, and of misdiagnosed subjects from 49-51% to 18%., Conclusions: Analysis of volatile organic compounds in exhaled air is a promising method to indicate NASH presence and absence. In comparison to plasma transaminase levels, the breath test significantly reduced the percentage of missed NASH patients and the number of unnecessarily biopsied subjects., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)