Identifying radiomics signatures in body composition imaging for the prediction of outcome following pancreatic cancer resection.

Background: Computerized radiological image analysis (radiomics) enables the investigation of image-derived phenotypes by extracting large numbers of quantitative features. We hypothesized that radiomics features may contain prognostic information that enhances conventional body composition analysis. We aimed to investigate whether body composition-associated radiomics features hold additional value over conventional body composition analysis and clinical patient characteristics used to predict survival of pancreatic ductal adenocarcinoma (PDAC) patients. Methods: Computed tomography images of 304 patients undergoing elective pancreatic cancer resection were analysed. 2D radiomics features were extracted from skeletal muscle and subcutaneous and visceral adipose tissue (SAT and VAT) compartments from a single slice at the third lumbar vertebra. The study population was randomly split (80:20) into training and holdout subsets. Feature ranking with Least Absolute Shrinkage Selection Operator (LASSO) followed by multivariable stepwise Cox regression in 1000 bootstrapped re-samples of the training data was performed and tested on the holdout data. The fitted regression predictors were used as "scores" for a clinical (C-Score), body composition (B-Score), and radiomics (R-Score) model. To stratify patients into the highest 25% and lowest 25% risk of mortality compared to the middle 50%, the Harrell Concordance Index was used. Results: Based on LASSO and stepwise cox regression for overall survival, ASA ≥3 and age were the most important clinical variables and constituted the C-score, and VAT-index (VATI) was the most important body composition variable and constituted the B-score. Three radiomics features (SATI_original_shape2D_Perimeter, VATI_original_glszm_SmallAreaEmphasis, and VATI_original_firstorder_Maximum) emerged as the most frequent set of features and yielded an R-Score. Of the mean concordance indices of C-, B-, and R-scores, R-score performed best (0.61, 95% CI 0.56-0.65, p<0.001), followed by the C-score (0.59, 95% CI 0.55-0.63, p<0.001) and B-score (0.55, 95% CI 0.50-0.60, p=0.03). Kaplan-Meier projection revealed that C-, B, and R-scores showed a clear split in the survival curves in the training set, although none remained significant in the holdout set. Conclusion: It is feasible to implement a data-driven radiomics approach to body composition imaging. Radiomics features provided improved predictive performance compared to conventional body composition variables for the prediction of overall survival of PDAC patients undergoing primary resection.

Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare.

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.

Morphological changes of the human face after massive weight-loss due to bariatric surgery.

The aim of this study was to evaluate the morphological changes in the face of obese patients during massive weight loss using a more reliable method than two dimensional photographs or tape measures. The faces of 23 patients were recorded prior to and six months after bariatric surgery. Distances between important anatomical landmarks of the face were calculated and the volume of the neck was compared. The distance between the Tragion and Subnasale (132.7 ± 6.804 mm to 131.5 ± 6.866 mm; p = 0.0003), and the distance between Tragion and Stomion became significantly longer 136.0 ± 8.016 mm to 134.3 ± 7.698 mm; p = 0.0031), while distances between the Tragion and Pogonion (150.2 ± 8.216 mm to 148.3 ± 8.383 mm; p < 0.0001), Tragion and Menton (152.3 ± 9.037 mm to 148.9 ± 9.623 mm; p < 0.0001), and Tragion and tip of the nose (144.9 ± 7.273 mm to 144.0 ± 7.416 mm; p = 0.0023) were significantly reduced. The mean volume loss of the neck was 75.218 ± 40.197 ml. No significant correlation was found between total weight loss and cervical volume loss (r = 0.3447; p = 0.1072). The morphological changes of the face after massive weight loss vary in different areas of the face. Patients and their attending physicians must be aware of the face's morphology change after massive weight loss in an extent that does not correlate with the total weight loss of the patient.

3D Optical Imaging as a New Tool for the Objective Evaluation of Body Shape Changes After Bariatric Surgery.

INTRODUCTION: Bariatric surgery is the most effective treatment option for obesity. It results in massive weight loss and improvement of obesity-related diseases. At the same time, it leads to a drastic change in body shape. These body shape changes are mainly measured by two-dimensional measurement methods, such as hip and waist circumference. These measurement methods suffer from significant measurement errors and poor reproducibility. Here, we present a three-dimensional measurement tool of the torso that can provide an objective and reproducible source for the detection of body shape changes after bariatric surgery. MATERIAL AND METHODS: In this study, 25 bariatric patients were scanned with Artec EVA®, an optical three-dimensional mobile scanner up to 1 week before and 6 months after surgery. Data were analyzed, and the volume of the torso, the abdominal circumference and distances between specific anatomical landmarks were calculated. The results of the processed three-dimensional measurements were compared with clinical data concerning weight loss and waist circumference. RESULTS: The volume of the torso decreased after bariatric surgery. Loss of volume correlated strongly with weight loss 6 months after the operation (r = 0.6425, p = 0.0005). Weight loss and three-dimensional processed data correlated better (r = 0.6121, p = 0.0011) than weight loss and waist circumference measured with a measuring tape (r = 0.3148, p = 0.1254). CONCLUSION: Three-dimensional imaging provides an objective and reproducible source for the detection of body shape changes after bariatric surgery. We recommend its use for the evaluation of central obesity, particularly for research issues and body imaging before and after bariatric surgery.

Serum levels of miR-29, miR-122, miR-155 and miR-192 are elevated in patients with cholangiocarcinoma.

OBJECTIVES: Cholangiocarcinoma (CCA) represents the second most common primary hepatic malignancy. Despite tremendous research activities, the prognosis for the majority of patients is still poor. Only in case of early diagnosis, liver resection might potentially lead to long-term survival. However, it is still unclear which patients benefit most from extensive liver surgery, highlighting the need for new diagnostic and prognostic stratification strategies. METHODS: Serum concentrations of a 4 miRNA panel (miR-122, miR-192, miR-29b and miR-155) were analyzed using semi-quantitative reverse-transcriptase PCR in serum samples from 94 patients with cholangiocarcinoma undergoing tumour resection and 40 healthy controls. Results were correlated with clinical data. RESULTS: Serum concentrations of miR-122, miR-192, miR-29b and miR-155 were significantly elevated in patients with CCA compared to healthy controls or patients with primary sclerosing cholangitis without malignant transformation. Although preoperative levels of these miRNAs were unsuitable as a prognostic marker of survival, a strong postoperative decline of miR-122 serum levels was significantly associated with a favorable patients' prognosis. CONCLUSIONS: Analysis of circulating miRNAs represents a promising tool for the diagnosis of even early stage CCA. A postoperative decline in miRNA serum concentrations might be indicative for a favorable patients' outcome and helpful to identify patients with a good prognosis after extended liver surgery.

Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients.

BACKGROUND: Hepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. METHODS: A retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level (L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. RESULTS: Univariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic (P = 0.035) and sarcopenic obese (P = 0.048) patients as well as a trend favoring obese (P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. CONCLUSIONS: Sarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.

A New Physiologic Mouse Model of One Anastomosis Gastric Bypass.

BACKGROUND: One anastomosis gastric bypass (OAGB) is a modern metabolic operation that has been demonstrated to be a rapid, safe, and effective procedure. As for other bariatric operations, the mechanisms and long-term effects of this procedure remain largely unknown and are difficult to address in human studies. Here, we present a new physiologic mouse model for mechanistic and long-term investigations. METHODS: Six-week-old C57Bl/6 mice were fed a high-fat diet for 12 weeks and scheduled for OAGB or sham operation. Mice were observed for 2 weeks after the operation, and weight and metabolic condition were monitored. RESULTS: Six mice were used to adapt the surgical technique. Afterwards, another 7 mice were scheduled for OAGB without further complications. The newly established OAGB procedure resulted in significant weight loss and improvement of glucose metabolism 2 weeks after the operation. CONCLUSIONS: The operation presented here is an easy-to-learn and physiologic mouse model of OAGB that can be used for further studies in mice.