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.

Bleeding management: rFVIIIFc in hemophilia A and liver transplantation.

BACKGROUND: In patients with severe hemophilia A prolonged bleeding may occur even in cases of minor trauma or surgery. OBJECTIVE: To investigate the feasibility and efficacy of a recombinant extended half-life (EHL) FVIII concentrate for perioperative bleeding management in a patient with severe hemophilia A undergoing liver transplantation. MATERIAL AND METHODS: Prior to transplantation FVIII activity and perioperatively required FVIII supply were estimated. In an individualized approach efmoroctocog alfa was supplemented if the intrinsic clotting time in the thrombelastometry was > 170 s. RESULTS: The patient perioperatively received a total of 28,000 IU efmoroctocog alfa. No signs of hemorrhage or complications were detected and no further intervention was necessary. CONCLUSION: The present case demonstrates that the use of an EHL FVIII is suitable for a successful perioperative bleeding control even in hemophilia patients at a high bleeding risk during major surgery. Due to the EHL constant FVIII levels could be achieved with relatively few injections. In order to confirm the obtained results, more real-world data in different operative settings are essential. Further research is needed on the use of thrombelastometry to guide substitution of factor VIII perioperatively.

Expression of Checkpoint Molecules in the Tumor Microenvironment of Intrahepatic Cholangiocarcinoma: Implications for Immune Checkpoint Blockade Therapy.

Background: The tumor microenvironment (TME) in cholangiocarcinoma (CCA) influences the immune environment. Checkpoint blockade is promising, but reliable biomarkers to predict response to treatment are still lacking. Materials and Methods: The levels of checkpoint molecules (PD-1, PD-L1, PD-L2, LAG-3, ICOS, TIGIT, TIM-3, CTLA-4), macrophages (CD68), and T cells (CD4 and CD8 cells) were assessed by multiplexed immunofluorescence in 50 intrahepatic cases. Associations between marker expression, immune cells, and region of expression were studied in the annotated regions of tumor, interface, sclerotic tumor, and tumor-free tissue. Results: ICCA demonstrated CD4_TIM-3 high densities in the tumor region of interest (ROI) compared to the interface (p = 0.014). CD8_PD-L1 and CD8_ICOS densities were elevated in the sclerotic tumor compared to the interface (p = 0.011 and p = 0.031, respectively). In a multivariate model, high expression of CD8_PD-L2 (p = 0.048) and CD4_ICOS_TIGIT (p = 0.011) was associated with nodal metastases. Conclusions: High densities of PD-L1 were more abundant in the sclerotic tumor region; this is meaningful for the stratification of immunotherapy. Lymph node metastasis correlates with CD4_ICOS_TIGIT co-expression and CD8_PD-L2 expression, indicating the checkpoint expression profile of patients with a poor prognosis. Also, multiple co-expressions occur, and this potentially suggests a role for combination therapy with different immune checkpoint targets than just PD-1 blockade monotherapy.

No difference in outcomes between large- and small-pore meshes in a prospective, randomized, multicenter trial investigating open retromuscular meshplasty for incisional hernia repair.

STUDY DESIGN: A randomized, controlled, prospective multicenter clinical trial with a parallel group design was initiated in eight surgical centers to compare a large-pore polypropylene mesh (Ultrapro®) to a small-pore polypropylene mesh (Premilene®) within a standardized retromuscular meshplasty for incisional hernia repair. METHODS: Between 2004 and 2006, patients with a fascial defect with a minimum diameter of 4 cm after vertical midline laparotomy were recruited for the trial. Patients underwent retromuscular meshplasty with either a large-pore or a small-pore mesh to identify the superiority of the large-pore mesh. Follow-up visits were scheduled at 5 and 21 days and 4, 12, and 24 months after surgery. A clinical examination, a modified short form 36 (SF-36®), a daily activity questionnaire, and an ultrasound investigation of the abdominal wall were completed at every follow-up visit. The primary outcome criterion was foreign body sensation at the 12-month visit, and the secondary endpoint criteria were the occurrence of hematoma, seroma, and chronic pain within 24 months postoperatively. RESULTS: In 8 centers, 181 patients were included in the study. Neither foreign body sensation within the first year after surgery (27.5% Ultrapro®, 32.2% Premilene®) nor the time until the first occurrence of foreign body sensation within the first year was significantly different between the groups. Regarding the secondary endpoints, no significant differences could be observed. At the 2-year follow-up, recurrences occurred in 5 Ultrapro® patients (5.5%) and 4 Premilene® patients (4.4%). CONCLUSION: Despite considerable differences in theoretical and experimental works, we have not been able to identify differences in surgical or patient-reported outcomes between the use of large- and small-pore meshes for retromuscular incisional hernia repair. TRIAL REGISTRATION: Clinical Trials NCT04961346 (16.06.2021) retrospectively registered.

Perioperative and long-term outcome of en-bloc arterial resection in pancreatic surgery.

BACKGROUND: Pancreatic tumors are frequently diagnosed in a locally advanced stage with poor prognosis if untreated. This study assesses the safety and oncological outcomes of pancreatic surgery with arterial en-bloc resection. METHODS: We retrospectively reviewed a prospectively maintained database of patients who underwent a pancreatic resection with arterial resection between 2011 and 2020. Univariable analyses were used to assess prognostic factors for survival. RESULTS: Forty consecutive patients (22 female; 18 male) undergoing arterial resections were included. Surgical procedures consisted of 19 pancreatoduodenectomies (PD, 48%), 16 distal splenopancreatectomy (DSP, 40%), and 5 total pancreatectomies (TP, 12%). Arterial resection included hepatic arteries (HA, N = 23), coeliac trunk (TC, N = 15) and superior mesenteric artery (SMA, N = 2). Neoadjuvant therapy was applied in 22 patients (58%). Major complications after surgery were observed in 15% of cases. 90-day mortality was 5%. Median disease-free survival and median overall survival were for the R0/CRM- group 22.8 months and 27.9 months, 9.5 and 19.8 months for the R0/CRM+ group, and 10.1 and 13.1 months for the R1 group, respectively. CONCLUSION: In highly selected patients, arterial en-bloc resection can be performed with acceptable mortality and morbidity rates and beneficial oncological outcome.

Safety of laparoscopic hepatectomy in patients with severe comorbidities - A propensity score matched analysis.

BACKGROUND: Laparoscopic hepatectomy (LH) is nowadays considered as the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after LH in patients with severe comorbidities are still sparse. METHODS: 247 patients, who underwent LH between January 2016 and March 2020 at European surgical center Aachen Maastricht (ESCAM) were retrospectively analyzed regarding surgical outcome. All patients were categorized according to the ASA guidelines and a propensity score matched (PSM) analysis was performed to compare patients with severe comorbidities with patients with minor or no comorbidities. RESULTS: After PSM, no statistically significant differences regarding clinical characteristics were observed. We performed major resections in 26.4% of h-ASA (ASA > 2) patients and 19.4% of l-ASA (ASA≤2) patients, respectively (P = .322). Overall morbidity (Clavien-Dindo≥1) was observed more frequently in the h-ASA group (h-ASA: 25.0% vs. l-ASA: 8.3%; P = .007) while analysis of major morbidity (Clavien-Dindo≥3b) showed a non-significant tendency for more complications in h-ASA patients (h-ASA: 8.3% vs. l-ASA: 1.4%; P = .053). A subgroup analysis identified major resection (HR = 5.05; P = .006) as an independent risk factor for the occurrence of any postoperative complication and chronic kidney disease (HR = 22.59; P = .030) and liver fibrosis (HR = 30.16; P = .031) as risk factors for the occurrence of major complications in h-ASA patients. CONCLUSION: LH in patients with severe systemic comorbidities shows a strong tendency towards an increased rate of major complications. Careful patient selection with respect to the planned extent of resection and the presence of chronic kidney disease and liver fibrosis should be performed to improve perioperative results.

Liver transplantation in malignant disease.

Liver transplantation for malignant disease has gained increasing attention as part of transplant oncology. Following the implementation of the Milan criteria, hepatocellular carcinoma (HCC) was the first generally accepted indication for transplantation in patients with cancer. Subsequently, more liberal criteria for HCC have been developed, and research on this topic is still ongoing. The evident success of liver transplantation for HCC has led to the attempt to extend its indication to other malignancies. Regarding perihilar cholangiocarcinoma, more and more evidence supports the use of liver transplantation, especially after neoadjuvant therapy. In addition, some data also show a benefit for selected patients with very early stage intrahepatic cholangiocarcinoma. Hepatic epithelioid hemangioendothelioma is a very rare but nonetheless established indication for liver transplantation in primary liver cancer. In contrast, patients with hepatic angiosarcoma are currently not considered to be optimal candidates. In secondary liver tumors, neuroendocrine cancer liver metastases are an accepted but comparability rare indication for liver transplantation. Recently, some evidence has been published supporting the use of liver transplantation even for colorectal liver metastases. This review summarizes the current evidence for liver transplantation for primary and secondary liver cancer.

Nerve Fibers in the Tumor Microenvironment as a Novel Biomarker for Oncological Outcome in Patients Undergoing Surgery for Perihilar Cholangiocarcinoma.

INTRODUCTION: Perihilar cholangiocarcinoma (pCCA) is a biliary tract cancer with a dismal prognosis, with surgery being the only chance of cure. A characteristic aggressive biological feature of pCCA is perineural growth which is defined by the invasion of cancer cells to nerves and nerve fibers. Recently, nerve fiber density (NFD) was linked to oncological outcomes in various malignancies; however, its prognostic role in pCCA remains to be elucidated. MATERIALS AND METHODS: Data of 101 pCCA patients who underwent curative-intent surgery between 2010 and 2019 were included in this study. Extensive group comparisons between patients with high and low NFD were carried out, and the association of cancer-specific survival (CSS) and recurrence-free survival with NFD and other clinicopathological characteristics was assessed using univariate and multivariable cox regression models. RESULTS: Patients with high NFD showed a median CSS of 90 months (95% CI: 48-132, 3-year CSS = 77%, 5-year CSS = 72%) compared to 33 months (95% CI: 19-47, 3-year CSS = 46%, 5-year CSS = 32%) in patients with low NFD (p = 0.006 log rank). Further, N1 category (HR = 2.84, p = 0.001) and high NFD (HR = 0.41, p = 0.024) were identified as independent predictors of CSS in multivariable analysis. Patients with high NFD and negative lymph nodes showed a median CSS of 90 months (3-year CSS = 88%, 5-year CSS = 80%), while patients with either positive lymph nodes or low NFD displayed a median CSS of 51 months (3-year CSS = 59%, 5-year CSS = 45%) and patients with both positive lymph nodes and low NFD a median CSS of 24 months (3-year CSS = 26%, 5-year CSS = 16%, p = 0.001 log rank). CONCLUSION: NFD has been identified as an important novel prognostic biomarker in pCCA patients. NFD alone and in combination with nodal status in particular allows to stratify pCCA patients based on their risk for inferior oncological outcomes after curative-intent surgery.

CT-Based Prediction of Liver Function and Post-PVE Hypertrophy Using an Artificial Neural Network.

BACKGROUND: This study aimed to evaluate whether hypertrophy after portal vein embolization (PVE) and maximum liver function capacity (LiMAx) are predictable by an artificial neural network (ANN) model based on computed tomography (CT) texture features. METHODS: We report a retrospective analysis on 118 patients undergoing preoperative assessment by CT before and after PVE for subsequent extended liver resection due to a malignant tumor at RWTH Aachen University Hospital. The LiMAx test was carried out in a subgroup of 55 patients prior to PVE. Associations between CT texture features and hypertrophy as well as liver function were assessed by a multilayer perceptron ANN model. RESULTS: Liver volumetry showed a median hypertrophy degree of 33.9% (16.5-60.4%) after PVE. Non-response, defined as a hypertrophy grade lower than 25%, was found in 36.5% (43/118) of the cases. The ANN prediction of the hypertrophy response showed a sensitivity of 95.8%, specificity of 44.4% and overall prediction accuracy of 74.6% (p < 0.001). The observed median LiMAx was 327 (248-433) µg/kg/h and was strongly correlated with the predicted LiMAx (R2 = 0.89). CONCLUSION: Our study shows that an ANN model based on CT texture features is able to predict the maximum liver function capacity and may be useful to assess potential hypertrophy after performing PVE.

Laparoscopic hepatectomy reduces postoperative complications and hospital stay in overweight and obese patients.

BACKGROUND: Laparoscopic liver surgery is currently considered the standard of care for various liver malignancies. However, studies focusing on perioperative outcome after laparoscopic hepatectomy (LH) in overweight patients are still sparse and its benefit compared to open hepatectomy (OH) is a matter of debate. AIM: To analyze postoperative outcomes in overweight [body mass index (BMI) over 25 kg/m²] and obese (BMI over 30 kg/m²) patients undergoing LH and compare postoperative outcome with patients undergoing OH. METHODS: Perioperative data of 68 overweight (BMI over 25 kg/m²) including a subcohort of obese (BMI over 30 kg/m²) patients (n = 27) who underwent LH at our institution between 2015 and 2019 were retrospectively analyzed regarding surgical outcome and compared to an equal number of patients undergoing OH. RESULTS: The mean BMI was 29.8 ± 4.9 kg/m2 in the LH group and 29.7 ± 3.6 kg/m2 in the OH group with major resections performed in 20.6% (LH) and 26.5% (OH) of cases, respectively. Operative time (194 ± 88 min vs 275 ± 131 min; P < 0.001) as well as intensive care (0.8 ± 0.7 d vs 1.1 ± 0.8 d; P = 0.031) and hospital stay (7.3 ± 3.6 d vs 15.7 ± 13.5 d; P < 0.001) were significant shorter in the LH group. Also, overall complications (20.6% vs 45.6%; P = 0.005) and major complications (1.5% vs 14.7%, P = 0.002) were observed less frequently after LH. An additional investigation analyzing the subgroup of obese patients who underwent LH (n = 27) and OH (n = 29) showed a shorter operative time (194 ± 81 min vs 260 ± 137 min; P = 0.009) and a reduced length of hospitalization (7.7 ± 4.3 d vs 17.2 ± 17 d; P < 0.001) but no difference in postoperative complications or overall cost. CONCLUSION: LH is safe and cost-effective in overweight and obese patients. Furthermore, LH is significantly associated with fewer postoperative complications and reduced hospital stay compared to OH in these patients.

Operative Time, Age, and Serum Albumin Predict Surgical Morbidity After Laparoscopic Liver Surgery.

Background. Laparoscopic liver resection (LLR) has emerged as a considerable alternative to conventional liver surgery. However, the increasing complexity of liver resection raises the incidence of postoperative complications. The aim of this study was to identify risk factors for postoperative morbidity in a monocentric cohort of patients undergoing LLR. Methods. All consecutive patients who underwent LLR between 2015 and 2019 at our institution were analyzed for associations between complications with demographics and clinical and operative characteristics by multivariable logistic regression analyses. Results. Our cohort comprised 156 patients who underwent LLR with a mean age of 60.0 ± 14.4 years. General complications and major perioperative morbidity were observed in 19.9% and 9.6% of the patients, respectively. Multivariable analysis identified age>65 years (HR = 2.56; P = .028) and operation time>180 minutes (HR = 4.44; P = .001) as significant predictors of general complications (Clavien ≥1), while albumin<4.3 g/dl (HR = 3.66; P = .033) and also operative time (HR = 23.72; P = .003) were identified as predictors of major postoperative morbidity (Clavien ≥3). Conclusion. Surgical morbidity is based on patient- (age and preoperative albumin) and procedure-related (operative time) characteristics. Careful patient selection is key to improve postoperative outcomes after LLR.

Short-term outcomes of laparoscopic versus open hepatectomy in the elderly patient: systematic review and meta-analysis.

BACKGROUND AND AIM: Favorable outcomes of laparoscopic hepatectomy (LH) over open hepatectomy (OH) have been demonstrated. LH offers less postoperative morbidity, less blood loss, and shorter hospital stay, while maintaining oncological safety. Only limited evidence about outcomes of LH in elderly is currently available. Therefore, this study aimed to compare short term outcomes of LH to OH for patients >65 years. METHODS: A systematic review and meta-analysis were performed according to Cochrane guidelines. Embase, PubMed, Cochrane Library, and Google Scholar were searched to identify eligible studies. Studies were included if they compared LH to OH, and focused on an elderly population, or had a majority of patients >65 years. Perioperative and postoperative outcomes were analyzed. RESULTS: Thirteen studies with 1174 patients (LH:532, OH:642) were included for analysis. When compared to OH, elderly undergoing LH had significantly less postoperative complications (risk ratio [RR]0.52; 95% confidence interval (CI):0.43-0.63), less blood loss (mean difference [MD]-198.58; 95% CI:-299.88 to -97.28), and shorter length of stay (MD-4.83; 95%CI:-7.91 to -1.84), while oncological safety was non-inferior (RR1.04; 95%CI:1.00-1.08). CONCLUSIONS: Within the elderly population LH seems to be superior to OH, concerning short-term outcomes. However, for broader applicability more trials are needed including more difficult and major resections.

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.

Primary Tumor Location Is a Prognostic Factor for Intrahepatic Progression-Free Survival in Patients with Colorectal Liver Metastases Undergoing Portal Vein Embolization as Preparation for Major Hepatic Surgery.

The aim of this study was to identify prognostic factors affecting intrahepatic progression-free survival (ihPFS) and overall survival (OS) in patients with colorectal cancer liver metastases (CRCLM) undergoing portal vein embolization (PVE) and subsequent (extended) right hemihepatectomy. A total of 59 patients (mean age: 60.8 ± 9.3 years) with CRCLM who underwent PVE in preparation for right hemihepatectomy were included. IhPFS and OS after PVE were calculated using the Kaplan-Meier method. Cox regression analyses were conducted to investigate the association between the following factors and survival: patient age, laterality of the colorectal cancer (right- versus left-sided), tumor location (colon versus rectal cancer), time of occurrence of hepatic metastases (synchronous versus metachronous), baseline number and size of hepatic metastases, presence or absence of metastases in the future liver remnant (FLR) before PVE, preoperative carcinoembryogenic antigen (CEA) levels, time between PVE and surgery, history of neoadjuvant or adjuvant chemotherapy, and the presence or absence of extrahepatic disease before PVE. Median follow up was 18 months. The median ihPFS was 8.2 months (95% confidence interval: 6.2-10.2 months), and median OS was 34.1 months (95% confidence interval: 27.3-40.9 months). Laterality of the primary colorectal cancer was the only statistically significant predictor of ihPFS after PVE (hazard ratio (HR) = 2.242; 95% confidence interval: 1.125, 4.465; p = 0.022), with patients with right-sided colorectal cancer having significantly shorter median ihPFS than patients with left-sided cancer (4.0 ± 1.9 months versus 10.2 ± 1.5 months; log rank test: p = 0.018). Other factors, in particular also the presence or absence of additional metastases in the FLR, were not associated with intrahepatic progression-free survival. The presence of extrahepatic disease was associated with worse OS (HR = 3.050, 95% confidence interval: 1.247, 7.459; p = 0.015).

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.

Noninvasive Evaluation of Liver Function in Morbidly Obese Patients.

BACKGROUND: More than half of the obese patients develop nonalcoholic fatty liver disease (NAFLD), which may further progress to nonalcoholic steatohepatitis (NASH) and cirrhosis. The aim of this study was to assess alterations in liver function in obese patients with a noninvasive liver function test. METHODS: In a prospective cohort study 102 morbidly obese patients undergoing bariatric surgery were evaluated for their liver function. Liver function capacity was determined by the LiMAx® test (enzymatic capacity of cytochrome P450 1A2). Liver biopsy specimens were obtained intraoperatively and classified according to the NAFLD Activity Score (NAS). NASH clinical score was additionally calculated from laboratory and clinical parameters. RESULTS: Median liver function capacity was 286 (IQR = 141) µg/kg/h. 27% of patients were histologically categorized as definite NASH, 39% as borderline, and 34% as not NASH. A significant correlation was observed between liver function capacity and NAS (r = -0.492; p < 0.001). The sensitivity and specificity of the LiMAx® test to distinguish between definite NASH and not NASH were 85.2% and 82.9% (AUROC 0.859), respectively. According to the NASH clinical scoring system, 14% were classified as low risk, 31% as intermediate, 26% as high, and 29% as very high risk. Liver function capacity is also significantly correlated with the NASH clinical scoring system (r = -0.411; p < 0.001). CONCLUSIONS: Obese patients show a diminished liver function capacity, especially those suffering from type 2 diabetes. The liver function capacity correlates with histological and clinical scoring systems. The LiMAx® test may be a valuable tool for noninvasive screening for NASH in obese patients.

Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation.

BACKGROUND: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma (HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points (exceptional MELD, exMELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional (neoadjuvant) treatment (LRT) is used. For patients unlikely to timely receive an organ via primary allocation, "extended critera donor (ECD) organs" are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. METHODS: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42 (84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients (82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. RESULTS: One- and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached (P = 0.487). LRT had no impact on overall survival (P = 0.629). Median waiting time was shorter if no LRT was performed (4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival (P = 0.663). CONCLUSIONS: Patients with an expected waiting time to transplantation of >6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.

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.