Laparoscopic Versus Open Hemihepatectomy: The ORANGE II PLUS Multicenter Randomized Controlled Trial.

PURPOSE: To compare outcomes after laparoscopic versus open major liver resection (hemihepatectomy) mainly for primary or metastatic cancer. The primary outcome measure was time to functional recovery. Secondary outcomes included morbidity, quality of life (QoL), and for those with cancer, resection margin status and time to adjuvant systemic therapy. PATIENTS AND METHODS: This was a multicenter, randomized controlled, patient-blinded, superiority trial on adult patients undergoing hemihepatectomy. Patients were recruited from 16 hospitals in Europe between November 2013 and December 2018. RESULTS: Of the 352 randomly assigned patients, 332 patients (94.3%) underwent surgery (laparoscopic, n = 166 and open, n = 166) and comprised the analysis population. The median time to functional recovery was 4 days (IQR, 3-5; range, 1-30) for laparoscopic hemihepatectomy versus 5 days (IQR, 4-6; range, 1-33) for open hemihepatectomy (difference, -17.5% [96% CI, -25.6 to -8.4]; P < .001). There was no difference in major complications (laparoscopic 24/166 [14.5%] v open 28/166 [16.9%]; odds ratio [OR], 0.84; P = .58). Regarding QoL, both global health status (difference, 3.2 points; P < .001) and body image (difference, 0.9 points; P < .001) scored significantly higher in the laparoscopic group. For the 281 (84.6%) patients with cancer, R0 resection margin status was similar (laparoscopic 106 [77.9%] v open 122 patients [84.1%], OR, 0.60; P = .14) with a shorter time to adjuvant systemic therapy in the laparoscopic group (46.5 days v 62.8 days, hazard ratio, 2.20; P = .009). CONCLUSION: Among patients undergoing hemihepatectomy, the laparoscopic approach resulted in a shorter time to functional recovery compared with open surgery. In addition, it was associated with a better QoL, and in patients with cancer, a shorter time to adjuvant systemic therapy with no adverse impact on cancer outcomes observed.

Students and physicians differ in perception of quality of life in patients with tumors of the upper gastrointestinal tract.

Health-related quality of life (HRQoL) has recently gained importance as treatment options for tumors of the upper GI tract lead to improved long-term survival. HRQoL is often estimated by physicians even though their reliability and the impact of outside factors such as contact time and level of medical education is unclear. Therefore, in this study we investigated the correlation between physicians', students', and patients' assessment of HRQoL. 54 patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaires EORTC QLQ-C30 and QLQ-OG25. Attending physicians and medical students filled out the same questionnaires through estimation of patients' HRQoL. Correlation was assessed through Pearson's and Kendall's τb coefficients. Physicians' and patients' assessments correlated for one out of six of the functional and a third of the symptom scores. Students' and patients' assessments correlated for one third of the functional and two thirds of the symptom scores. Students tended to underestimate patients' symptom burden while physicians tended to overestimate it. Physicians failed to correctly assess several pathognomonic symptoms in this study. Students showed higher correlation with patients' symptoms than physicians. Even so, this adds to mounting evidence that shows the benefit of using patient-reported outcomes as a gold standard regarding HRQoL.

Quality of Life, Sarcopenia and Nutritional Status in Patients with Esophagogastric Tumors before and after Neoadjuvant Therapy.

(1) Background: Health-related quality of life (HRQoL) gains importance as novel treatment options for individuals with esophagogastric tumors to improve long-term survival. Impaired HRQoL has been shown to be a predictor of overall survival. Sarcopenia is a known prognostic factor for postoperative complications. As the regular control of sarcopenia through CT scans might not always be possible and HRQoL and nutritional scores are easier to obtain, this study aimed to assess the relationship between nutritional scores, HRQoL and skeletal muscle mass in patients undergoing chemotherapy for cancers of the upper gastrointestinal tract. (2) Methods: Eighty patients presenting with tumors of the upper GI tract were included and asked to fill out the standardized HRQoL questionnaire, EORTC's QLQ-C30. Nutritional status was assessed using the MNA, MUST and NRS 2002 scores. Sarcopenia was determined semi-automatically based on the skeletal muscle index at the L3 vertebrae level in staging CT scans. (3) Results: In chemo-naïve patients, HRQoL summary scores correlated significantly with nutritional scores and SMI. SMI and HRQoL prior to neoadjuvant therapy correlated significantly with SMI after treatment. (4) Conclusions: HRQoL is a helpful tool for assessing patients' overall constitution. The correlation of HRQoL summary scores and SMI might allow for a rough assessment of skeletal muscle status through HRQoL assessment in chemo-naïve patients.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Body composition is associated with postoperative complications in perihilar cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA. METHODS: All patients with pCCA who underwent curative-intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan-Meier analysis to evaluate oncological risk factors in the study cohort. RESULTS: BC was frequently altered in patients undergoing curative-intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien-Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no-sarcopenia, 21 months vs. 32 months, p = 0.048 log rank). CONCLUSIONS: BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.

Living-Donor Liver Transplantation for a Large Hepatocellular Carcinoma in a Genetically Identical Twin Sister.

Hepatocellular carcinoma (HCC) is, to date, the most common malignant tumor of the liver and is commonly staged with the Milan criteria. While deceased-donor liver transplantations (DDLT) are reserved for patients within the Milan criteria, living-donor liver transplantation (LDLT) might be a curative option for patients outside the Milan criteria. We here report a case of a 32-year-old woman who developed a giant, unresectable HCC out of a hepatocellular adenoma (HCA) after a pregnancy. The genetically identical twin sister donated her left hemi-liver after ethical approval and preoperative screening. No long-term immunosuppressive therapy was necessary, and after more than eight years, both are in perfect health and the recipient gave birth to a second child. This case shows that in certain situations large HCCs outside the standard criteria can be cured by LT. Careful evaluation of both donor and recipient should be performed for indications like this to assure optimal clinical outcome.

Laparoscopic Living donor liver transplantation in irresectable intrahepatic cholangiocarcinoma in primary sclerosing cholangitis associated liver cirrhosis.

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver tumor and usually associated with a poor oncological prognosis. The current gold standard is the surgical resection of the tumor with subsequent adjuvant therapy. However, in case of irresectability e.g. in case of liver cirrhosis, a palliative treatment regime is conducted.This report demonstrates the case of an irresectable iCCA in liver cirrhosis due to primary sclerosing cholangitis (PSC) treated by living-donor liver transplantation (LDLT) facilitated by minimal invasive donor hepatectomy. No postoperative complications were observed in the donor and the donor was released on the 6th postoperative day. Further, after a follow-up of 1.5 years, no disease recurrence was detected in the recipient.According to the recent international literature, liver transplantation can be evaluated in case of small solitary iCCA (< 3 cm) in cirrhosis. Less evidence is provided for transplantation in advanced tumors which are surgically not resectable due to advanced liver disease or infiltration of major vessels, however some reports display adequate long-term survival after strict patient selection. The selection criteria comprise the absence of distant metastases and locoregional lymph node metastases as well as partial remission or stable disease after neoadjuvant chemotherapy. Due to no established graft allocation for iCCA in Germany, LDLT is currently the best option to realize transplantation in these patients. Developments in the last decade indicate that LDLT should preferentially be performed in minimal invasive manner (laparoscopic or robotic) as this approach is associated with less overall complications and a shorter hospitalization. The presented case illustrates the possibilities of modern surgery and the introduction of transplant oncology in the modern therapy of patients combining systemic therapy, surgical resection and transplantation to achieve optimal long-term results in patients which were initially indicated for palliative treatment.

Time to surgery is not an oncological risk factor in patients with cholangiocarcinoma undergoing curative-intent liver surgery.

Surgical resection is the only option to achieve long-term survival in cholangiocellular carcinoma (CCA). Due to limitations of health care systems and unforeseeable events, e.g., the COVID pandemic, the time from diagnosis to surgery (time-to-surgery (TTS)) has gained great interest in malignancies. Thus, we investigated whether TTS is associated with the oncological outcome in patients who underwent surgery for CCA. A cohort of 276 patients undergoing curative-intent surgery for intrahepatic and perihilar CCA excluding individuals with neoadjuvant therapy and perioperative mortality between 2010 and 2021 were eligible for analysis. Patients were grouped according to TTS (≤ 30; 31-60; 61-90; > 90 days) and compared by Kruskal-Wallis-analysis. Survival was compared using Kaplan-Meier analysis and characteristics associated with cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) using Cox regressions. The median CSS was 39 months (3-year-CSS = 52%, 5-year-CSS = 42%) and the median RFS 20 months (3-year-CSS = 38%, 5-year-CSS = 33%). In univariable Cox regressions, TTS was not associated with CSS (p = 0.971) or RFS (p = 0.855), respectively. A grouped analysis with respect to TTS (≤ 30 days, n = 106; 31-60 days, n = 134; 61-90 days, n = 44; > 90 days, n = 29) displayed a median CSS of 38, 33, 51 and 41 months and median RFS of 17, 22, 28 and 20 months (p = 0.971 log rank; p = 0.520 log rank). No statistical difference regarding oncological risk factors were observed between the groups. This study is the first comprehensive analysis of TTS in CCA patients. Within a representative European cohort, TTS was not associated with earlier tumor recurrence or reduced CCS.

Impact of Altered Body Composition on Clinical and Oncological Outcomes in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a common primary liver tumor with limited treatment options and poor prognosis. Changes in body composition (BC) have been shown to affect the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC and clinical and oncological outcomes in patients with iCCA. All patients with iCCA who had surgery from 2010 to 2022 at our institution were included. We used CT scans and 3D Slicer software to assess BC and conducted logistic regressions as well as Cox regressions and Kaplan-Meier analyses to investigate associations between BC and clinical variables with focus on postoperative complications and oncological outcomes. BC was frequently altered in iCCA (n = 162), with 53.1% of the patients showing obesity, 63.2% sarcopenia, 52.8% myosteatosis, 10.1% visceral obesity, and 15.3% sarcopenic obesity. The multivariate analysis showed no meaningful association between BC and perioperative complications. Myosteatosis was associated with reduced overall survival (OS) in iCCA patients (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016 log rank). Further, the subgroup analysis revealed a notable effect in the subset of R0-resected patients (myosteatosis vs. non-myosteatosis, 18 vs. 32 months, p = 0.025) and patients with nodal metastases (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016). While altered BC is not associated with perioperative outcomes in iCCA, myosteatosis emerges as a prognostic factor for reduced OS in the overall and sub-populations of resected patients.

Hepatocellular loss of mTOR aggravates tumor burden in nonalcoholic steatohepatitis-related HCC.

Obesity and associated nonalcoholic steatohepatitis (NASH) are on the rise globally. NASH became an important driver of hepatocellular carcinoma (HCC) in recent years. Activation of the central metabolic regulator mTOR (mechanistic target of rapamycin) is frequently observed in HCCs. However, mTOR inhibition failed to improve the outcome of HCC therapies, demonstrating the need for a better understanding of the molecular and functional consequences of mTOR blockade. We established a murine NASH-driven HCC model based on long-term western diet feeding combined with hepatocellular mTOR-inactivation. We evaluated tumor load and whole-body fat percentage via µCT-scans, analyzed metabolic blood parameters and tissue proteome profiles. Additionally, we used a bioinformatic model to access liver and HCC mitochondrial metabolic functions. The tumor burden was massively increased via mTOR-knockout. Several signs argue for extensive metabolic reprogramming of glucose, fatty acid, bile acid and cholesterol metabolism. Kinetic modeling revealed reduced oxygen consumption in KO-tumors. NASH-derived HCC pathogenesis is driven by metabolic disturbances and should be considered separately from those caused by other etiologies. We conclude that mTOR functions as tumor suppressor in hepatocytes especially under long-term western diet feeding. However, some of the detrimental consequences of this diet are attenuated by mTOR blockade.

Pharmaceutical Interventions for Inpatients with Liver Cirrhosis and Liver Transplantation: A Systematic Review of Experimental Studies.

Liver cirrhosis, which is considered one of the leading causes of death in the world, can lead to severe complications, and is often followed by a liver transplantation. These patients take an average of nine medications daily. If not managed adequately, it can be accompanied by serious drug-related problems. To reduce this risk, a clinical pharmacist may be included as part of the healthcare team to optimize medication therapy in this population. This study aimed to systematically identify the pharmaceutical interventions which reduced drug-related problems and improved medication therapy for adult hospitalized liver cirrhotic and liver transplant patients when compared to standard care. Three databases (PubMed, Embase, and CENTRAL) were systematically searched from the inception of each database to 25 October 2023, and interventional studies in the English language were included. The risk of bias was assessed according to RoB-I for the UBA study and RoB2 for the identified RCT. The detected interventions to reduce drug-related problems in liver cirrhotic and liver transplant patients were extracted and classified according to a "Hierarchy of Controls" model. Two studies from Germany and the USA met our inclusion criteria, respectively. In these studies, we identified two interventions that included education, expert consultation, and the monitoring of the immunosuppressive medications serum level. The main objective of the two included studies was improving patients' compliance through adherence. These pharmaceutical interventions identified were classified as administrative controls, which is one of the lowest levels in the "Hierarchy of Controls" with which to address a potential risk. Pharmaceutical interventions to optimize medication therapy were found to be rare in the examined population, and were limited to "administrative controls". These interventions were limited to transplant patients' education and the monitoring of the immunosuppressive medication serum levels. No interventional studies were found to have investigated pharmaceutical interventions in patients with liver cirrhosis. Especially regarding this patient group, future studies to reduce DRPs using pharmaceutical interventions are needed. This study received no external funding and its PROSPERO registration number is CRD42022309122.

Survival after combined resection and ablation is not inferior to that after resection alone, in patients with four or more colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. METHODS: This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010-2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. RESULTS: Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan-Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. CONCLUSION: For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease.

Value of prognostic scoring systems in the era of multimodal therapy for recurrent colorectal liver metastases.

BACKGROUND: Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS: Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION: The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.

Insulin Resistance Is the Main Characteristic of Metabolically Unhealthy Obesity (MUO) Associated with NASH in Patients Undergoing Bariatric Surgery.

(1) Background: Metabolically healthy obesity (MHO) is a concept that applies to obese patients without any elements of metabolic syndrome (metS). In turn, metabolically unhealthy obesity (MUO) defines the presence of elements of metS in obese patients. The components of MUO can be divided into subgroups regarding the elements of inflammation, lipid and glucose metabolism and cardiovascular disease. MUO patients appear to be at greater risk of developing non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) compared to MHO patients. The aim of this study was to evaluate the influence of different MUO components on NAFLD and NASH in patients with morbid obesity undergoing bariatric surgery. (2) Methods: 141 patients undergoing bariatric surgery from September 2015 and October 2021 at RWTH Aachen university hospital (Germany) were included. Patients were evaluated pre-operatively for characteristics of metS and MUO (HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension). Intraoperatively, a liver biopsy was taken from the left liver lobe and evaluated for the presence of NAFLD or NASH. In ordinal regression analyses, different factors were evaluated for their influence on NAFLD and NASH. (3) Results: Mean BMI of the patients was 52.3 kg/m2 (36-74.8, SD 8.4). Together, the parameters HbA1c, HOMA, CRP, BMI, fasting glucose, LDL, TG, HDL and the presence of arterial hypertension accounted for a significant amount of variance in the outcome, with a likelihood ratio of χ2 (9) = 41.547, p < 0.001, for predicting the presence of NASH. Only HOMA was an independent predictor of NASH (B = 0.102, SE = 0.0373, p = 0.007). Evaluation of steatosis showed a similar trend (likelihood ratio χ2 (9) = 40.272, p < 0.001). Independent predictors of steatosis were HbA1c (B = 0.833, SE = 0.343, p = 0.015) and HOMA (B = 0.136, SE = 0.039, p < 0.001). (4) Conclusions: The above-mentioned model, including components of MUO, was significant for diagnosing NASH in patients with morbid obesity undergoing bariatric surgery. Out of the different subitems, HOMA independently predicted the presence of NASH and steatosis, while HbA1c independently predicted steatosis and fibrosis. Taken together, the parameter of glucose metabolism appears to be more accurate for the prediction of NASH than the parameters of lipid metabolism, inflammation or the presence of cardiovascular disease.

Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection.

PURPOSE: Given limitations of the health care systems in case of unforeseeable events, e.g., the COVID pandemic as well as trends in prehabilitation, time from diagnosis to surgery (time to surgery, (TTS)) has become a research issue in malignancies. Thus, we investigated whether TTS is associated with oncological outcome in HCC patients undergoing surgery. METHODS: A monocentric cohort of 217 patients undergoing liver resection for HCC between 2009 and 2021 was analyzed. Individuals were grouped according to TTS and compared regarding clinical characteristics. Overall survival (OS) and recurrence-free survival (RFS) was compared using Kaplan-Meier analysis and investigated by univariate and multivariable Cox regressions. RESULTS: TTS was not associated with OS (p=0.126) or RFS (p=0.761) of the study cohort in univariate analysis. In multivariable analysis age (p=0.028), ASA (p=0.027), INR (0.016), number of HCC nodules (p=0.026), microvascular invasion (MVI; p<0.001), and postoperative complications (p<0.001) were associated with OS and INR (p=0.005), and number of HCC nodules (p<0.001) and MVI (p<0.001) were associated with RFS. A comparative analysis of TTS subgroups was conducted (group 1, ≤30 days, n=55; group 2, 31-60 days, n=79; group 3, 61-90 days, n=45; group 4, >90 days, n=38). Here, the median OS were 62, 41, 38, and 40 months (p=0.602 log rank) and median RFS were 21, 26, 26, and 25 months (p=0.994 log rank). No statistical difference regarding oncological risk factors were observed between these groups. CONCLUSION: TTS is not associated with earlier tumor recurrence or reduced overall survival in surgically treated HCC patients.

Successful Transplantation of a Liver from a Donor with HELLP Syndrome Undergoing Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Implantation.

BACKGROUND Liver transplantation (LT) has become the treatment of choice for patients with end-stage liver disease (ESLD). The organ shortage forced clinicians to use livers from donors with certain risk factors, so-called extended-criteria donor (ECD) organs. Hypothermic oxygenated machine perfusion (HOPE) is an alternative to conventional static cold storage and reduces early allograft injury in ECD organs. In this article we present the case of a 45-year-old man with hepatitis B virus (HBV)-associated cirrhosis and hepatocellular carcinoma (HCC) who underwent successful liver transplantation supported by pretransplant hypothermic oxygenated machine perfusion (HOPE) from a 34-year-old extended-criteria donor (ECD) with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. CASE REPORT Liver transplantation was scheduled for a 45-year-old man with hepatocellular carcinoma (HCC) due to hepatitis B virus-induced liver cirrhosis. The organ donor was a 34-year-old woman who had developed intracerebral hemorrhage and brain death due to HELLP syndrome after delivery. Compared to the day of admission to the intensive care unit, a decrease in the donor's transaminases was observed prior to organ procurement. Before transplantation, HOPE was conducted after regular back-table preparation of the graft. LT was performed according to the standard surgical techniques and a standardized immunosuppressive regimen was conducted. In the post-transplant period, transaminases peaked directly after the operation and normalized after 1 week. No major surgical complications occurred. The patient was discharged after a 24-day hospital stay with normal liver function. CONCLUSIONS This case report supports the benefits of using HOPE in ECD organs and it should be considered in livers of donors with HELLP syndrome to improve post-transplant outcome.

Optical coherence tomography combined with convolutional neural networks can differentiate between intrahepatic cholangiocarcinoma and liver parenchyma ex vivo.

PURPOSE: Surgical resection with complete tumor excision (R0) provides the best chance of long-term survival for patients with intrahepatic cholangiocarcinoma (iCCA). A non-invasive imaging technology, which could provide quick intraoperative assessment of resection margins, as an adjunct to histological examination, is optical coherence tomography (OCT). In this study, we investigated the ability of OCT combined with convolutional neural networks (CNN), to differentiate iCCA from normal liver parenchyma ex vivo. METHODS: Consecutive adult patients undergoing elective liver resections for iCCA between June 2020 and April 2021 (n = 11) were included in this study. Areas of interest from resection specimens were scanned ex vivo, before formalin fixation, using a table-top OCT device at 1310 nm wavelength. Scanned areas were marked and histologically examined, providing a diagnosis for each scan. An Xception CNN was trained, validated, and tested in matching OCT scans to their corresponding histological diagnoses, through a 5 × 5 stratified cross-validation process. RESULTS: Twenty-four three-dimensional scans (corresponding to approx. 85,603 individual) from ten patients were included in the analysis. In 5 × 5 cross-validation, the model achieved a mean F1-score, sensitivity, and specificity of 0.94, 0.94, and 0.93, respectively. CONCLUSION: Optical coherence tomography combined with CNN can differentiate iCCA from liver parenchyma ex vivo. Further studies are necessary to expand on these results and lead to innovative in vivo OCT applications, such as intraoperative or endoscopic scanning.

Health-related quality of life outcomes following Roux-en-Y gastric bypass versus one anastomosis gastric bypass.

PURPOSE: Roux-en-Y gastric bypass (RYGB) and one anastomosis gastric bypass (OAGB) are effective standard bariatric surgeries with comparable weight loss and remission of obesity-related comorbidities. As procedure-specific health-related quality of life (HrQoL) outcomes have not been directly compared thus far, we conducted this questionnaire-based study. METHODS: Two hundred forty patients after undergoing either RYGB or OAGB between 2011 and 2016 were contacted and asked to fill out SF36 and BAROS questionnaires. All statistical analysis was performed with Microsoft Excel and GraphPad Prism. Primary objectives were procedure-dependent differences in HrQoL. Secondary objectives were weight loss and remission of comorbidities. RESULTS: One hundred nineteen of 240 contacted patients (49.6%) replied, 58 after RYGB (48.7%) and 61 after OAGB (51.3%). Follow-up period was < 24 months in 52 and > 24 months in 64 evaluable patients. The mean age was 46 years (range 23 to 71). Regarding the < 24 months groups, both physical and psychological SF36 sum scales were comparably high. Only the subcategory "general health perception" was significantly better after RYGB. Significantly higher excess weight loss (EWL) after RYGB (88.81%) compared to OAGB (66.25%) caused significantly better global < 24 months BAROS outcomes, whereas remission of comorbidities and HrQoL was similar. Both > 24 months groups showed high SF36-HrQoL sum scales. Global mean BAROS results after > 24 months were "very good" in both procedures. EWL in RYGB (80.81%) and in OAGB (81.36%) were comparably excellent. CONCLUSION: Concerning SF36 and BAROS evaluated HrQoL in early and late postoperative phases, both procedures demonstrated comparable and relevant improvements. Further (preferably randomized) studies should include evaluation of preoperative HrQoL.

Telomere length dynamics measured by flow-FISH in patients with obesity undergoing bariatric surgery.

Obesity has negative effects on comorbidities, health-related quality of life and survival. Telomere length (TL) changes after bariatric surgery have been reported, but the studies are contradictory, and analyses using state-of-the art techniques for TL measurement, such as flow-FISH, are sparse. We measured TL dynamics via flow-FISH in patients undergoing bariatric surgery and compared their TL with 105 healthy individuals. Patients with obesity who underwent bariatric surgery were included. Lymphocyte and granulocyte absolute and age-adjusted (aa) TL were analyzed by flow-FISH before (preoperative cohort, n = 45) and after surgery (follow-up cohort, n = 35) at month 5.5 ± 3.9 (mean ± standard deviation [SD]). The initial lymphocyte aaTL was significantly shorter (-0.37 kb ± 0.18 kb, P = 0.045) in patients with obesity, while the granulocyte aaTL was not different from that in the healthy comparison population (0.28 kb ± 0.17 kb, P = 0.11). The telomere dynamics after surgery showed an increase in mean TL in both lymphocytes and granulocytes of patients with a pronounced BMI loss of ≥ 10 kg/m2. We did not find any association between TL increase after surgery and age, sex or the type of procedure selected for bariatric surgery. We confirmed that patients suffering from obesity have significantly shorter lymphocyte TL using flow-FISH. Along with and dependent on the degree of weight reduction after bariatric surgery, TL significantly increased in both lymphocytes and granulocytes after a mean of 5.5 months. Our results show that bariatric surgery affects not only body weight but also biomarkers of aging, such as TL.

Calcification of the visceral aorta and celiac trunk is associated with renal and allograft outcomes after deceased donor liver transplantation.

PURPOSE: Atherosclerosis affects clinical outcomes in the setting of major surgery. Here we aimed to investigate the prognostic role of visceral aortic (VAC), extended visceral aortic (VAC+), and celiac artery calcification (CAC) in the assessment of short- and long-term outcomes following deceased donor orthotopic liver transplantation (OLT) in a western European cohort. METHODS: We retrospectively analyzed the data of 281 consecutive recipients who underwent OLT at a German university medical center (05/2010-03/2020). The parameters VAC, VAC+, or CAC were evaluated by preoperative computed tomography-based calcium quantification according to the Agatston score. RESULTS: Significant VAC or CAC were associated with impaired postoperative renal function (p = 0.0016; p = 0.0211). Patients with VAC suffered more frequently from early allograft dysfunction (EAD) (38 vs 26%, p = 0.031), while CAC was associated with higher estimated procedural costs (p = 0.049). In the multivariate logistic regression analysis, VAC was identified as an independent predictor of EAD (2.387 OR, 1.290-4.418 CI, p = 0.006). Concerning long-term graft and patient survival, no significant difference was found, even though patients with calcification showed a tendency towards lower 5-year survival compared to those without (VAC: 65 vs 73%, p = 0.217; CAC: 52 vs 72%, p = 0.105). VAC+ failed to provide an additional prognostic value compared to VAC. CONCLUSION: This is the first clinical report to show the prognostic role of VAC/CAC in the setting of deceased donor OLT with a particular value in the perioperative phase. Further studies are warranted to validate these findings. CT computed tomography, OLT orthotopic liver transplantation.