Sarcopenic Obesity Promotes Recurrence in Patients Undergoing Resection for Colorectal Liver Metastases (CRLM).

BACKGROUND/AIM: Sarcopenia, is predictive of a worse outcome after resection for colorectal liver metastases (CRLM). Obesity leads to a metabolic double burden if sarcopenia is as present, prompting malignancy progression, known as sarcopenic obesity (SO). This study aimed to compare sarcopenia and SO in patients undergoing CRLM resection, to prognostic parameters. PATIENTS AND METHODS: The skeletal muscle index (SMI) defined sarcopenia using sex specific cut off values (48.4 cm2/m2 for females and 59.1 cm2/m2 for males) by calculating the preoperative muscle mass at the vertebral height L3 using OSIRIX DICOM viewer. SO was determined as sarcopenia in patients showing obesity, as shown via fat percentage measurements on the preoperative CT scan. Established prognostic parameters (KRAS status, TNM classification, inflammatory response) were evaluated against SMI and SO to assess their predictability for postoperative outcomes. RESULTS: A total of 251 patients (62% female, median age 68 years) were included. Sarcopenic patients showed a threefold higher risk for postoperative death as compared to non-sarcopenic patients (p=0.04). Prevalent SO increased this risk to fivefold (p=0.01) compared to non-sarcopenic patients. COX regression analysis revealed SO and KRAS positivity as independent prognostic factors for disease-free survival (SO: p=0.038; KRAS: p=0.041; TNM, tumor size, Charlson Comorbidity Index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio all not significant). Patients risk of death in case of KRAS positivity and SO was seven times higher (p=0.03). CONCLUSION: There seems to be a benefit in merging data on mutational status and muscle wasting in patients with CRLM to facilitate an individual, patient-tailored approach.

Mechanical upper bowel obstruction caused by a large trichobezoar in a young woman: A very unusual case report.

BACKGROUND: Bezoars usually compile human fibers and debris. A special form of bezoar in case of psychologically altered individuals is the trichobezoar. It consists of voluntarily swallowed hair bulks and is normally removed via gastroscopy. Trichobezoars leading to ileus have rarely been reported. CASE SUMMARY: A 24-year-old female patient presented to the emergency room with abdominal pain, nausea, and vomiting for 3 d. Her previous medical and psychiatric history was unremarkable. Laboratory analysis showed iron deficiency anemia, leukocytosis, and elevated liver enzymes. An abdominal CT scan revealed a dense structure in the patients' stomach which turned out to be a huge trichobezoar completely obstructing the pylorus. The trichobezoar had to be removed surgically. During her postoperative course, a subcutaneous seroma formed. After a single puncture, the rest of the recovery process was unremarkable, and the patient recovered fully. CONCLUSION: A mechanical bowel obstruction is a potentially life-threatening event for every patient. In our case a young female was suffering from severe symptoms of an obstruction which might have resulted in serious harm without successful surgical management.

Genetic Modulation: Future Trends Toward Graft Optimization During Machine Perfusion.

Dynamic preservation methods such as normothermic, subnormothermic, and hypothermic machine perfusion circuits have emerged as viable alternatives to conventional static cold storage. These organ perfusion technologies serve as preservation methods and enable organ assessment, reconditioning, and repair before transplantation. Gene therapy is a novel strategy with the potential to transform the field of graft optimization and treatment. Thereby specific pathways involved in the transplantation process can be targeted and modified. This review aims to provide an overview of gene delivery methods during ex vivo machine perfusion of kidney and liver grafts. Recent literature on state-of-the-art gene therapy approaches during ex situ organ preservation, especially with respect to ischemia-reperfusion injury, as well as acute and chronic graft rejection have been analyzed. Additionally, potential challenges that could affect further refinement of this therapeutic modality are outlined.

Prediction of Biliary Complications After Human Liver Transplantation Using Hyperspectral Imaging and Convolutional Neural Networks: A Proof-of-concept Study.

BACKGROUND: Biliary complications (BCs) negatively impact the outcome after liver transplantation. We herein tested whether hyperspectral imaging (HSI) generated data from bile ducts (BD) on reperfusion and machine learning techniques for data readout may serve as a novel approach for predicting BC. METHODS: Tissue-specific data from 136 HSI liver images were integrated into a convolutional neural network (CNN). Fourteen patients undergoing liver transplantation after normothermic machine preservation served as a validation cohort. Assessment of oxygen saturation, organ hemoglobin, and tissue water levels through HSI was performed after completing the biliary anastomosis. Resected BD segments were analyzed by immunohistochemistry and real-time confocal microscopy. RESULTS: Immunohistochemistry and real-time confocal microscopy revealed mild (grade I: 1%-40%) BD damage in 8 patients and moderate (grade II: 40%-80%) injury in 1 patient. Donor and recipient data alone had no predictive capacity toward BC. Deep learning-based analysis of HSI data resulted in >90% accuracy of automated detection of BD. The CNN-based analysis yielded a correct classification in 72% and 69% for BC/no BC. The combination of HSI with donor and recipient factors showed 94% accuracy in predicting BC. CONCLUSIONS: Deep learning-based modeling using CNN of HSI-based tissue property data represents a noninvasive technique for predicting postoperative BC.

Incidence of Diabetes Mellitus and Its Impact on Outcomes in Patients Undergoing Surgical Pancreatectomy for Non-Malignant and Malignant Pancreatobiliary Diseases-A Retrospective Analysis.

Diabetes mellitus (DM) is a prominent risk factor for malignant and non-malignant pancreatic diseases. Furthermore, the presence of DM predicts an unfavourable outcome in people with pancreatic cancer. This retrospective observational study investigated 370 patients who underwent pancreatic resection surgery for various indications (84.3% in malignant indication) in a single surgery centre in Graz, Austria. The preoperative and postoperative diabetes statuses were evaluated according to surgery method and disease entity and predictors for diabetes development after surgery, as well as outcomes (survival and cancer recurrence) according to diabetes status, were analysed. In the entire cohort, the postoperative diabetes (postopDM) incidence was 29%. PostopDM occurred significantly more frequently in malignoma patients than in those with benign diseases (31.3% vs. 16.7%; p = 0.040, OR = 2.28). In the malignoma population, BMI, longer surgery duration, and prolonged ICU and hospital stay were significant predictors of diabetes development. The 1- and 2-year follow-ups showed a significantly increased mortality of people with postopDM in comparison to people without diabetes (HR 1-year = 2.02, p = 0.014 and HR 2-years = 1.56, p = 0.034). Local cancer recurrence was not influenced by the diabetes status. Postoperative new-onset diabetes seems to be associated with higher mortality of patients with pancreatic malignoma undergoing pancreatobiliary surgery.

Gallstone as a cause of intestinal obstruction (Bouveret syndrome).

Gallstone ileus is a rare cause of bowel obstruction. Here we report about two cases with clinical findings and therapy options. Both patients were presented with typical ileus-like symptoms, although the surgical treatment differs due to the CT scan and intraoperative findings. There are many methods for treating patients with Bouveret syndrome. Endoscopy should be the first treatment option for young patients with no significant diseases in the medical history, depending on the size of the stone. Surgical approach is the next possible option. Combination of these two methods is associated with higher mortality. In case there is no extraluminal gas or intraperitoneal fluid in CT-scan, there is no need for an acute surgery. Conservative therapy prior to the intervention enables a precise planning of whether the endoscopic approach or open surgery would be beneficial for the patient.

Pharmacokinetics of immunosuppressive agents during hemoperfusion in a sheep model.

Introduction: Hemoadsorption shows promising signals in organ preservation and post lung transplantation. However, its potential impact on the pharmacokinetics of immunosuppressant drugs (ID) is still unknown. Methods: In this interventional study, CytoSorb® hemoperfusion was tested in healthy sheep (n = 5) against a sham extracorporeal circuit (n = 3). Seven different ID (tacrolimus (TAC), cyclosporin A (CYA), mycophenolate mofetil (MMF), everolimus (EVER), basiliximab (BAS), methylprednisolone (MP) and prednisolone (PRED)) were administered in clinically relevant doses and combinations. Their levels were measured repeatedly in blood samples from the extracorporeal circulation over 6 h following administration. Population pharmacokinetic modeling analysis (NONMEM® 7.5) was performed. Results: Negligible clearance was observed for PRED and BAS. For all other substances, a saturable adsorption sub-model with linear decrease of the adsorption effect over the adsorbed amount best described the measured concentrations. The maximum absolute adsorbed amounts (95% CI) for TAC, CYA, MMF, EVER, and MP were 0.040 (0.028-0.053), 1.15 (0.39-1.91), 4.17 (2.00-6.35), 0.0163 (0.007-0.026), and 53.4 mg (20.9-85.9), respectively, indicating an adsorption of less than 5% of the daily administered dosages for all investigated substances. Discussion: In this large animal model, CytoSorb® hemoperfusion appears to have a limited effect on the clearance of tested ID.

CT Texture Analysis and Node-RADS CT Score of Lymph Nodes in Patients With Perihilar Cholangiocarcinoma.

BACKGROUND/AIM: Texture analysis can provide quantitative imaging markers from computed tomography (CT) images. The Node-RADS classification was recently published as a classification system to better characterize lymph nodes in oncological imaging. The present analysis investigated the diagnostic benefit of CT texture analysis and the Node-RADS classification to categorize and stage lymph nodes in patients with perihilar cholangiocarcinoma. PATIENTS AND METHODS: Overall, 25 patients (n=9 females, 36%) with a mean age of 72.4±8.1 years were included. All patients were surgically resected and the lymph nodes were histopathologically analyzed. CT-texture analysis was performed with the Mazda package. All investigated lymph nodes were scored in accordance with the Node-RADS classification. RESULTS: Regarding lymph node discrimination (N- versus N+), Node-RADS classification achieved an area under the curve (AUC) of 0.86 resulting in a sensitivity of 78% and a specificity of 86%. Multiple investigated texture features were different between negative and positive lymph nodes. The "S(0,1)SumVarnc" achieved the best AUC of 0.75 resulting in a sensitivity of 0.91 and a specificity of 0.67. Correlation analysis showed various statistically significant associations between CT texture features and Node-RADS score. CONCLUSION: Several CT texture features and the Node-RADS score derived from preoperative staging CT were associated with the malignancy of the hilar lymph nodes and might aid for preoperative staging. This could change surgical treatment planning in hilar cholangiocarcinoma.

Effect of Pre-Transplant Recipient Underweight on the Postoperative Outcome and Graft Survival in Primary Kidney Transplantation.

BACKGROUND: The objective of this study was to evaluate the influence of recipient underweight on the short- and long-term outcomes of patients undergoing primary kidney transplantation (KT). PATIENTS AND METHODS: Three hundred thirty-three patients receiving primary KT in our department between 1993 and 2017 were included in the study. Patients were divided according to their body mass index (BMI) into underweight (BMI <18.5 kg/m2; N = 29) and normal weight (BMI 18.5-24.9 kg/m2; N = 304) groups. Clinicopathological characteristics, postoperative outcomes, and graft and patient survival were analyzed retrospectively. RESULTS: The postoperative rate of surgical complications and renal function were comparable between the groups. One year and 3 years after KT, 70% and 92.9%, respectively, of the pre-transplant underweight patients reached a normal BMI (≥18.5 kg/m2). The mean death-censored graft survival was significantly lower in pre-transplant underweight patients than in pre-transplant normal-weight patients (11.5 ± 1.6 years vs 16.3 ± 0.6 years, respectively; P = .045). Especially KT recipients with a moderate or severe pre-transplant underweight (BMI <17 kg/m2; N = 8) showed an increased rate of graft loss (5- and 10-year graft survival: 21.4% each). No statistical difference could be observed between the 2 groups regarding causes of graft loss. In multivariate analysis, recipient underweight (P = .024) remained an independent prognostic factor for graft survival. CONCLUSION: Being underweight did not affect the early postoperative outcome after primary KT. However, underweight, and especially moderate and severe thinness, is associated with reduced long-term kidney graft survival, and therefore this group of patients should be monitored with special attention.

Donor derived hematopoietic stem cell niche transplantation facilitates mixed chimerism mediated donor specific tolerance.

Compelling experimental evidence confirms that the robustness and longevity of mixed chimerism (MC) relies on the persistence and availability of donor-derived hematopoietic stem cell (HSC) niches in recipients. Based on our prior work in rodent vascularized composite allotransplantation (VCA) models, we hypothesize that the vascularized bone components in VCA bearing donor HSC niches, thus may provide a unique biologic opportunity to facilitate stable MC and transplant tolerance. In this study, by utilizing a series of rodent VCA models we demonstrated that donor HSC niches in the vascularized bone facilitate persistent multilineage hematopoietic chimerism in transplant recipients and promote donor-specific tolerance without harsh myeloablation. In addition, the transplanted donor HSC niches in VCA facilitated the donor HSC niches seeding to the recipient bone marrow compartment and contributed to the maintenance and homeostasis of stable MC. Moreover, this study provided evidences that chimeric thymus plays a role in MC-mediated transplant tolerance through a mechanism of thymic central deletion. Mechanistic insights from our study could lead to the use of vascularized donor bone with pre-engrafted HSC niches as a safe, complementary strategy to induce robust and stable MC-mediated tolerance in VCA or solid organ transplantation recipients.

Prediction of the Postoperative Outcome in Liver Resection Using Perioperative Serum Lactate Levels.

BACKGROUND: The aim of our study was to analyze perioperative lactate levels and their predictive value for postoperative mortality and morbidity after liver resection. METHODS: The clinicopathological characteristics and outcomes of 152 patients who underwent liver resection for benign and malign diagnoses were analyzed retrospectively. Lactate concentrations at three different time points, (1) before liver resection (LAC-PRE), (2) after liver resection on day 0 (LAC-POST), and (3) on day one after the operation (LAC-POD1) were assessed regarding the prognostic value in predicting postoperative complications and mortality according to the Clavien-Dindo (CD) classification. RESULTS: The rates of postoperative complications (CD ≥ IIIb) and mortality rates were 19.7% (N = 30) and 4.6% (N = 7), respectively. The LAC-PRE levels showed no correlation with the postoperative outcome. The ROC curve analysis showed that LCT-POST and LCT-POD1 values were moderately strong in predicting postoperative morbidity (0.681 and 0.768, respectively) and had strong predictive accuracies regarding postoperative mortality (0.800 and 0.838, respectively). The multivariate analysis revealed LAC-POST as a significant predictor of postoperative complications (CD ≥ IIIb: OR 9.28; 95% CI: 2.88-29.9; p < 0.001) and mortality (OR 11.69; 95% CI: 1.76-77.7; p = 0.011). CONCLUSION: Early postoperative lactate levels are a useful and easily practicable predictor of postoperative morbidity and mortality in patients after liver resection.

Alternative intraoperative optical imaging modalities for fluorescence angiography in gastrointestinal surgery: spectral imaging and imaging photoplethysmography.

INTRODUCTION: Intraoperative near-infrared fluorescence angiography with indocyanine green (ICG-FA) is a well-established modality in gastrointestinal surgery. Its main drawback is the application of a fluorescent agent with possible side effects for patients. The goal of this review paper is the presentation of alternative, non-invasive optical imaging methods and their comparison with ICG-FA. MATERIAL AND METHODS: The principles of ICG-FA, spectral imaging, imaging photoplethysmography (iPPG), and their applications in gastrointestinal surgery are described based on selected published works. RESULTS: The main applications of the three modalities are the evaluation of tissue perfusion, the identification of risk structures, and tissue segmentation or classification. While the ICG-FA images are mainly evaluated visually, leading to subjective interpretations, quantitative physiological parameters and tissue segmentation are provided in spectral imaging and iPPG. The combination of ICG-FA and spectral imaging is a promising method. CONCLUSIONS: Non-invasive spectral imaging and iPPG have shown promising results in gastrointestinal surgery. They can overcome the main drawbacks of ICG-FA, i.e. the use of contrast agents, the lack of quantitative analysis, repeatability, and a difficult standardization of the acquisition. Further technical improvements and clinical evaluations are necessary to establish them in daily clinical routine.

Dickkopf-Related Protein 1 as Response Marker for Transarterial Chemoembolization of Hepatocellular Carcinomas.

Background and Aims: In the treatment of hepatocellular carcinoma (HCC), response prediction to transarterial chemoembolization (TACE) based on serum biomarkers is not established. We have studied the association of circulating Dickkopf-related protein 1 (DKK-1) with baseline characteristics and response to TACE in European HCC patients. Methods: Patients with HCC treated with TACE from 2010 to 2018 at a tertiary referral hospital were retrospectively enrolled. Levels of DKK-1 were measured in serum samples collected before TACE. Response was assessed according to mRECIST criteria at week 12 after TACE. Results: Ninety-seven patients were enrolled, including seventy-nine responders and eighteen refractory. Before TACE, median DKK-1 serum levels were 922 [range, 199−4514] pg/mL. DKK-1 levels were lower in patients with liver cirrhosis (p = 0.002) and showed a strong correlation with total radiologic tumor size (r = 0.593; p < 0.001) and with Barcelona Clinic Liver Cancer stages (p = 0.032). Median DKK-1 levels were significantly higher in refractory patients as compared to responders (1471 pg/mL [range, 546−2492 pg/mL] versus 837 pg/mL [range, 199−4515 pg/mL]; p < 0.001), and DKK-1 could better identify responders than AFP (AUC = 0.798 vs. AUC = 0.679; p < 0.001). A DKK-1 cutoff of ≤1150 pg/mL was defined to identify responders to TACE with a sensitivity of 78% and specificity of 77%. DKK-1 levels were suitable to determine response to TACE in patients with low AFP serum levels (AFP levels < 20 ng/mL; AUC = 0.843; 95% CI [0.721−0.965]; p = 0.003). Conclusion: DKK-1 levels in serum are strongly associated tumor size and with response to TACE in European HCC patients, including those patients with low AFP levels.

Predictive Value of HAS-BLED Score Regarding Bleeding Events and Graft Survival following Renal Transplantation.

Objective: Due to the high prevalence and incidence of cardio- and cerebrovascular diseases among dialysis-dependent patients with end-stage renal disease (ERSD) scheduled for kidney transplantation (KT), the use of antiplatelet therapy (APT) and/or anticoagulant drugs in this patient population is common. However, these patients share a high risk of complications, either due to thromboembolic or bleeding events, which makes adequate peri- and post-transplant anticoagulation management challenging. Predictive clinical models, such as the HAS-BLED score developed for predicting major bleeding events in patients under anticoagulation therapy, could be helpful tools for the optimization of antithrombotic management and could reduce peri- and postoperative morbidity and mortality. Methods: Data from 204 patients undergoing kidney transplantation (KT) between 2011 and 2018 at the University Hospital Leipzig were retrospectively analyzed. Patients were stratified and categorized postoperatively into the prophylaxis group (group A)­patients without pretransplant anticoagulation/antiplatelet therapy and receiving postoperative heparin in prophylactic doses­and into the (sub)therapeutic group (group B)­patients with postoperative continued use of pretransplant antithrombotic medication used (sub)therapeutically. The primary outcome was the incidence of postoperative bleeding events, which was evaluated for a possible association with the use of antithrombotic therapy. Secondary analyses were conducted for the associations of other potential risk factors, specifically the HAS-BLED score, with allograft outcome. Univariate and multivariate logistic regression as well as a Cox proportional hazard model were used to identify risk factors for long-term allograft function, outcome and survival. The calibration and prognostic accuracy of the risk models were evaluated using the Hosmer−Lemshow test (HLT) and the area under the receiver operating characteristic curve (AUC) model. Results: In total, 94 of 204 (47%) patients received (sub)therapeutic antithrombotic therapy after transplantation and 108 (53%) patients received prophylactic antithrombotic therapy. A total of 61 (29%) patients showed signs of postoperative bleeding. The incidence (p < 0.01) and timepoint of bleeding (p < 0.01) varied significantly between the different antithrombotic treatment groups. After applying multivariate analyses, pre-existing cardiovascular disease (CVD) (OR 2.89 (95% CI: 1.02−8.21); p = 0.04), procedure-specific complications (blood loss (OR 1.03 (95% CI: 1.0−1.05); p = 0.014), Clavien−Dindo classification > grade II (OR 1.03 (95% CI: 1.0−1.05); p = 0.018)), HAS-BLED score (OR 1.49 (95% CI: 1.08−2.07); p = 0.018), vit K antagonists (VKA) (OR 5.89 (95% CI: 1.10−31.28); p = 0.037), the combination of APT and therapeutic heparin (OR 5.44 (95% CI: 1.33−22.31); p = 0.018) as well as postoperative therapeutic heparin (OR 3.37 (95% CI: 1.37−8.26); p < 0.01) were independently associated with an increased risk for bleeding. The intraoperative use of heparin, prior antiplatelet therapy and APT in combination with prophylactic heparin was not associated with increased bleeding risk. Higher recipient body mass index (BMI) (OR 0.32 per 10 kg/m2 increase in BMI (95% CI: 0.12−0.91); p = 0.023) as well as living donor KT (OR 0.43 (95% CI: 0.18−0.94); p = 0.036) were associated with a decreased risk for bleeding. Regarding bleeding events and graft failure, the HAS-BLED risk model demonstrated good calibration (bleeding and graft failure: HLT: chi-square: 4.572, p = 0.802, versus chi-square: 6.52, p = 0.18, respectively) and moderate predictive performance (bleeding AUC: 0.72 (0.63−0.79); graft failure: AUC: 0.7 (0.6−0.78)). Conclusions: In our current study, we could demonstrate the HAS-BLED risk score as a helpful tool with acceptable predictive accuracy regarding bleeding events and graft failure following KT. The intensified monitoring and precise stratification/assessment of bleeding risk factors may be helpful in identifying patients at higher risks of bleeding, improved individualized anticoagulation decisions and choices of antithrombotic therapy in order to optimize outcome after kidney transplantation.

[Artificial intelligence and hyperspectral imaging for image-guided assistance in minimally invasive surgery]. / Künstliche Intelligenz und hyperspektrale Bildgebung zur bildgestützten Assistenz in der minimal-invasiven Chirurgie.

BACKGROUND: Intraoperative imaging assists surgeons during minimally invasive procedures. Hyperspectral imaging (HSI) is a noninvasive and noncontact optical technique with great diagnostic potential in medicine. The combination with artificial intelligence (AI) approaches to analyze HSI data is called intelligent HSI in this article. OBJECTIVE: What are the medical applications and advantages of intelligent HSI for minimally invasive visceral surgery? MATERIAL AND METHODS: Within various clinical studies HSI data from multiple in vivo tissue types and oncological resections were acquired using an HSI camera system. Different AI algorithms were evaluated for detection and discrimination of organs, risk structures and tumors. RESULTS: In an experimental animal study 20 different organs could be differentiated with high precision (> 95%) using AI. In vivo, the parathyroid glands could be discriminated from surrounding tissue with an F1 score of 47% and sensitivity of 75%, and the bile duct with an F1 score of 79% and sensitivity of 90%. Furthermore, ex vivo tumor tissue could be successfully detected with an area under the receiver operating characteristic (ROC) curve (AUC) larger than 0.91. DISCUSSION: This study demonstrates that intelligent HSI can automatically and accurately detect different tissue types. Despite great progress in the last decade intelligent HSI still has limitations. Thus, accurate AI algorithms that are easier to understand for the user and an extensive standardized and continuously growing database are needed. Further clinical studies should support the various medical applications and lead to the adoption of intelligent HSI in the clinical routine practice.

Magnetic Resonance Imaging of Peritoneal Carcinomatosis: Evaluation of High b-Value Computed Diffusion-Weighted Imaging.

Over the last few years, diffusion-weighted imaging (DWI) has become increasingly relevant in the diagnostic assessment of peritoneal carcinomatosis. The aim of this study was to investigate the benefits of high-b DWI (c-DWI) compared to standard DWI in patients with peritoneal carcinomatosis. A cohort of 40 patients with peritoneal carcinomatosis were included in this retrospective study. DWI was performed with b-values of 50, 400, and 800 or 1000 s/mm² on a 1.5-T magnetic resonance imaging (MRI) scanner. C-DWI was calculated using a mono-exponential model with high b-values of 1000, 2000, 3000, 4000, and 5000 s/mm². All c-DWI images with high b-values were compared in terms of volume, detectability of peritoneal lesions, and image quality with the DWI sequence acquired with a b-value of 800 or 1000 s/mm² by two readers. In the group with a b-value of 800 s/mm², there was no statistically significant difference in terms of lesion volume. In the second group with a b-value of 1000 s/mm², peritoneal carcinomatosis lesions were statistically significantly larger than in the c-DWI with a- high b-value of 2000 s/mm² (median 7 cm³, range 1−26 cm³vs. median 6 cm³, range 1−83 cm³, p < 0.05). In both groups, there was a marked decrease in the detectability of peritoneal lesions starting at b = 2000 s/mm². In addition, image quality decreased noticeably from c-DWI at b = 3000 s/mm². In both groups, all images with high b-values at b = 4000 s/mm² and 5000 s/mm² were not diagnostically valuable due to poor image quality. The c-DWI technique offers good diagnostic performance without additional scanning time. High c-DWI b-values up to b = 1000 s/mm² provide comparable detectability of peritoneal carcinomatosis compared to standard DWI. Higher b-values over 1500 s/mm² result in lower image quality, which might lead to misdiagnosis.

Analysis of Volatile Anesthetic-Induced Organ Protection in Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: Despite recent advances in surgical procedures and immunosuppressive regimes, early pancreatic graft dysfunction, mainly specified as ischemia-reperfusion injury (IRI)-Remains a common cause of pancreas graft failure with potentially worse outcomes in simultaneous pancreas-kidney transplantation (SPKT). Anesthetic conditioning is a widely described strategy to attenuate IRI and facilitate graft protection. Here, we investigate the effects of different volatile anesthetics (VAs) on early IRI-associated posttransplant clinical outcomes as well as graft function and outcome in SPKT recipients. METHODS: Medical data of 105 patients undergoing SPKT between 1998-2018 were retrospectively analyzed and stratified according to the used VAs. The primary study endpoint was the association and effect of VAs on pancreas allograft failure following SPKT; secondary endpoint analyses included "IRI- associated posttransplant clinical outcome" as well as long-term graft function and outcome. Additionally, peak serum levels of C-reactive protein (CRP) and lipase during the first 72 h after SPKT were determined and used as further markers for "pancreatic IRI" and graft injury. Typical clinicopathological characteristics and postoperative outcomes such as early graft outcome and long-term function were analyzed. RESULTS: Of the 105 included patients in this study three VAs were used: isoflurane (n = 58 patients; 55%), sevoflurane (n = 22 patients; 21%), and desflurane (n = 25 patients, 24%). Donor and recipient characteristics were comparable between both groups. Early graft loss within 3 months (24% versus 5% versus 8%, p = 0.04) as well as IRI-associated postoperative clinical complications (pancreatitis: 21% versus 5% versus 5%, p = 0.04; vascular thrombosis: 13% versus 0% versus 5%; p = 0.09) occurred more frequently in the Isoflurane group compared with the sevoflurane and desflurane groups. Anesthesia with sevoflurane resulted in the lowest serum peak levels of lipase and CRP during the first 3 days after transplantation, followed by desflurane and isoflurane (p = 0.039 and p = 0.001, respectively). There was no difference with regard to 10-year pancreas graft survival as well as endocrine/metabolic function among all three VA groups. Multivariate analysis revealed the choice of VAs as an independent prognostic factor for graft failure three months after SPKT (HR 0.38, 95%CI: 0.17-0.84; p = 0.029). CONCLUSIONS: In our study, sevoflurane and desflurane were associated with significantly increased early graft survival as well as decreased IRI-associated post-transplant clinical outcomes when compared with the isoflurane group and should be the focus of future clinical studies evaluating the positive effects of different VA agents in patients receiving SPKT.

Hyperspectral Imaging as a Tool for Viability Assessment During Normothermic Machine Perfusion of Human Livers: A Proof of Concept Pilot Study.

Normothermic machine perfusion (NMP) allows for ex vivo viability and functional assessment prior to liver transplantation (LT). Hyperspectral imaging represents a suitable, non-invasive method to evaluate tissue morphology and organ perfusion during NMP. Liver allografts were subjected to NMP prior to LT. Serial image acquisition of oxygen saturation levels (StO2), organ hemoglobin (THI), near-infrared perfusion (NIR) and tissue water indices (TWI) through hyperspectral imaging was performed during static cold storage, at 1h, 6h, 12h and at the end of NMP. The readouts were correlated with perfusate parameters at equivalent time points. Twenty-one deceased donor livers were included in the study. Seven (33.0%) were discarded due to poor organ function during NMP. StO2 (p < 0.001), THI (p < 0.001) and NIR (p = 0.002) significantly augmented, from static cold storage (pre-NMP) to NMP end, while TWI dropped (p = 0.005) during the observational period. At 12-24h, a significantly higher hemoglobin concentration (THI) in the superficial tissue layers was seen in discarded, compared to transplanted livers (p = 0.036). Lactate values at 12h NMP correlated negatively with NIR perfusion index between 12 and 24h NMP and with the delta NIR perfusion index between 1 and 24h (rs = -0.883, p = 0.008 for both). Furthermore, NIR and TWI correlated with lactate clearance and pH. This study provides first evidence of feasibility of hyperspectral imaging as a potentially helpful contact-free organ viability assessment tool during liver NMP.

Functional changes of the gastric bypass microbiota reactivate thermogenic adipose tissue and systemic glucose control via intestinal FXR-TGR5 crosstalk in diet-induced obesity.

BACKGROUND: Bariatric surgery remains the most effective therapy for adiposity reduction and remission of type 2 diabetes. Although different bariatric procedures associate with pronounced shifts in the gut microbiota, their functional role in the regulation of energetic and metabolic benefits achieved with the surgery are not clear. METHODS: To evaluate the causal as well as the inherent therapeutic character of the surgery-altered gut microbiome in improved energy and metabolic control in diet-induced obesity, an antibiotic cocktail was used to eliminate the gut microbiota in diet-induced obese rats after gastric bypass surgery, and gastric bypass-shaped gut microbiota was transplanted into obese littermates. Thorough metabolic profiling was combined with omics technologies on samples collected from cecum and plasma to identify adaptions in gut microbiota-host signaling, which control improved energy balance and metabolic profile after surgery. RESULTS: In this study, we first demonstrate that depletion of the gut microbiota largely reversed the beneficial effects of gastric bypass surgery on negative energy balance and improved glucolipid metabolism. Further, we show that the gastric bypass-shaped gut microbiota reduces adiposity in diet-induced obese recipients by re-activating energy expenditure from metabolic active brown adipose tissue. These beneficial effects were linked to improved glucose homeostasis, lipid control, and improved fatty liver disease. Mechanistically, these effects were triggered by modulation of taurine metabolism by the gastric bypass gut microbiota, fostering an increased abundance of intestinal and circulating taurine-conjugated bile acid species. In turn, these bile acids activated gut-restricted FXR and systemic TGR5 signaling to stimulate adaptive thermogenesis. CONCLUSION: Our results establish the role of the gut microbiome in the weight loss and metabolic success of gastric bypass surgery. We here identify a signaling cascade that entails altered bile acid receptor signaling resulting from a collective, hitherto undescribed change in the metabolic activity of a cluster of bacteria, thereby readjusting energy imbalance and metabolic disease in the obese host. These findings strengthen the rationale for microbiota-targeted strategies to improve and refine current therapies of obesity and metabolic syndrome. Video Abstract Bariatric Surgery (i.e. RYGB) or the repeated fecal microbiota transfer (FMT) from RYGB donors into DIO (diet-induced obesity) animals induces shifts in the intestinal microbiome, an effect that can be impaired by oral application of antibiotics (ABx). Our current study shows that RYGB-dependent alterations in the intestinal microbiome result in an increase in the luminal and systemic pool of Taurine-conjugated Bile acids (TCBAs) by various cellular mechanisms acting in the intestine and the liver. TCBAs induce signaling via two different receptors, farnesoid X receptor (FXR, specifically in the intestines) and the G-protein-coupled bile acid receptor TGR5 (systemically), finally resulting in metabolic improvement and advanced weight management. BSH, bile salt hydrolase; BAT brown adipose tissue.