Sarcopenic obesity may predict worse liver regeneration after right graft living donor liver transplantation.

Sarcopenic obesity impairs the outcome after liver transplantation. The effect of this on liver regeneration has not yet been studied. The aim of this study was to evaluate the potential effect of body composition changes on liver volume gain after living donor liver transplantation. We observed liver regeneration in 100 patients who underwent living donor liver transplantation using right lobe grafts (Segments V-VIII). Liver volumetry and body composition analysis were performed based on CT images with special software. The gain of liver volume was calculated between 2 points in time considering the absolute and percentage values: before surgery and early after surgery, with a median time of 10 days. Pearson's correlation and multivariate analysis using stepwise multiple regression were used to examine the potential correlation between body composition and liver volume gain. The liver volume increase was significantly negatively correlated with adipose tissue in the body stem ( r = -0.4, p < 0.001) and positively correlated with psoas mass ( r = 0.24, p = 0.02). These results correspond with those of the multiple regression analysis, which indicated adipose tissue (ß = -1.0, p < 0.001) and psoas mass (ß = 0.12, p < 0.001). The presence of malignancy as an indication for liver transplantation was another significant independent factor negatively affecting liver growth (ß = -13.1, p = 0.046). Sarcopenic obesity predicts an impaired liver volume increase after living donation. This could worsen the postoperative outcome. The role of alimentary interventions and exercises in improving body composition and thus postoperative outcome should be evaluated through prospective interventional studies.

Auxilliary Liver Transplantation According to the RAPID Procedure in Noncirrhotic Patients: Technical Aspects and Early Outcomes.

OBJECTIVE: To present technical details and short-term experiences of liver transplantation as a 2-stage procedure using small for size grafts in a multicenter cohort study. BACKGROUND: Two-stage liver transplantation using small for size grafts should be a feasible procedure with lower morbidity and mortality rates. Retrospective cohort study between 2015 and 2022 with multicenter experience. Twenty-three resection and partial liver transplantation with delayed total hepatectomy procedures for noncirrhotic indications were performed in 6 European centers (20 with grafts from living donors and 3 after deceased donation). Procedure's feasibility, graft volumetric changes, morbidity, and mortality of donor and recipient were explored. RESULTS: There was a low donor morbidity (4.3%) in our cohort. Hypertrophy of the graft was rapid (mean graft volume increases 107% between both stages) and offered the opportunity for remnant hepatectomy after a median of 14 days. In all cases, portomesenteric flow was routed to the graft by right remnant portal vein ligation. Portal vein inflow modulation to alleviate transient harmful portal hypertension was not needed in any case. Early postoperative mortality (4.3%) of the recipients were low. Ten patients suffered from complications ≥IIIb according to the Clavien-Dindo classification. CONCLUSIONS: Two-stage liver transplantation is a feasible option for noncirrhotic patients allowing the safe use of small for size grafts and could possibly be extended with caution to liver diseases with portal hypertension and cirrhosis. The resection and partial liver transplantation with delayed total hepatectomy technique might be a viable option for expanding the donor pool given the current organ shortage especially for low-model of end stage liver disease patients.

[Individualized curative treatment for malignant diseases through liver transplantation]. / Individualisierte kurative Therapie bei malignen Erkrankungen durch Lebertransplantation.

BACKGROUND: For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions. OBJECTIVE: This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies. RESULTS AND CONCLUSION: Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.

Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy.

PURPOSE: This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS: The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS: Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS: Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.

Critical Evaluation of Discarded Donor Livers in the Eurotransplant Region: Potential Implications for Machine Perfusion.

BACKGROUND There are still many offered donor livers that are declined during the allocation process. Machine perfusion offers the option to evaluate (especially marginal) donor organs and to better decide whether a graft has the potential of being transplanted or not. There is a lack of clear detailed data on why organs are declined and how many donor livers would have the potential of being evaluated in the machine. MATERIAL AND METHODS We retrospectively reviewed 1356 donor livers between 2016 and 2018, which were offered by Eurotransplant and were declined during the allocation process; 284 grafts were from donor after cardiac death (DCD) and 1072 donations were from after brain death (DBD). The analysis was performed independently and blinded by senior transplant surgeons. RESULTS There were 904 (66.6%) donor livers with potential to be evaluated as suitable grafts in machine perfusion, whereas 417 (30.8%) organs were definitely not-transplantable, mainly due to liver cirrhosis, (untreated) donor malignancy, cardiac diseases of the donor leading to a hepatic congestion, and/or systemic infections in the donor. Donors in blood group "AB" were disproportionally often rejected. Due to missing data, 35 (2.6%) organs could not be sufficiently evaluated. CONCLUSIONS Our data suggest that many declined donor livers have potential of being evaluated by machine perfusion. Comprehensive use of machine perfusion is necessary and useful to improve the current organ shortage.

Liver Transplantation for Incidental Cholangiocarcinoma or Combined Hepatocellular Carcinoma/Cholangiocarcinoma-Own Experiences and Review of the Literature.

BACKGROUND: Data about liver transplantation for mixed tumors from hepatocellular carcinoma to cholangiocarcinoma are limited. Furthermore, the diagnosis of intrahepatic cholangiocarcinoma or combined tumors in a cirrhotic liver is considered a contraindication for transplantation. Our aim was to evaluate the long-term outcomes of patients with incidental cholangiocarcinoma or combined tumors after liver transplantation. METHODS: In our descriptive analysis, data were evaluated from all patients since 2010 who received a liver transplant due to an assumed hepatocellular carcinoma at Jena University Hospital. Survival rates were determined using the Kaplan-Meier method. RESULTS: Between January 2010 and December 2022, an incidental intrahepatic cholangiocarcinoma was found in eight patients post-transplant. Four combined hepatocellular and cholangiocarcinoma and four sole intrahepatic cholangiocarcinomas were found. A recurrence through distant metastases from combined hepatocellular- and cholangiocarcinoma was found in one patient at one year after transplantation. Another patient developed a pulmonary primary tumor independently one year post-transplant. The recurrence rate was at 14.3%. While two patients died, the 1- and 5-year overall survival rates post-transplant were 87.5% and 75%, respectively. CONCLUSION: Patients with intrahepatic cholangiocarcinoma or combined hepatocellular- and cholangiocarcinoma could profit from liver transplantation.

Liver regeneration after two-stage liver transplantation is more effective than after other preconditioning procedures in colorectal liver metastases.

INTRODUCTION: Induction of liver regeneration represents an option to expand the resectability in patients with expected small future liver remnant (FLR). The aim of this cohort-study is to compare the liver regeneration between different surgical procedures, including novel procedures such as two-stage living donor liver transplantation using small-for-size grafts. METHODS: Forty-three patients with colorectal liver metastases were included between 2004 and 2020. They underwent one of the following three procedures: portal vein embolization (PVE), associated liver partition with portal vein ligation for staged hepatectomy (ALPPS), and living donor two-stage liver transplantation (LT). The volume gain of the future liver remnant was analyzed in comparison between the three mentioned procedures. RESULTS: The type of surgery performed had a significant correlation with liver regeneration with a strong effect on the benefit of ALPPS and liver transplantation, respectively (r = .6, p = .00003). The type of surgery was the only independent co-factor in the multiple regression, which showed a significant influence on FLR-increase favoring two-stage transplantation compared to the other two related procedures (ß = .12, T = 3.9, p = .0004). The histological and immunohistochemical studies also showed a clear advantage of proliferation to the benefits of two-stage liver transplantation compared with ALPPS. CONCLUSION: Two-stage liver transplantation using small-for-size grafts induces better FLR-increase than portal vein embolization or ALPPS in patients with colorectal liver metastases.

Postoperative Outcomes in 415 Patients Following Liver Transplantation Using Extended Donor Criteria: A Study from a Single Center in Germany.

BACKGROUND Because of the massive organ shortage worldwide, marginal organs are increasingly being considered. The aim of this study was to present a comprehensive analysis of donor-related factors clinically supposed to influence the outcome after liver transplantation. This study from a single center in Germany aimed to evaluate postoperative outcomes in 415 patients following liver transplantation using extended donor criteria. MATERIAL AND METHODS Extended donor criteria (EDC) were considered according to the official guidelines issued through the German Medical Association. Other factors and the Eurotransplant Donor Risk Index (ET-DRI) were also considered. Correlation studies, logistic regression, and Kaplan-Meier-estimator were used to evaluate the outcome. RESULTS The postoperative outcomes with or without EDC were comparable. Other factors had an impact on early allograft failure (EAD), including male donors (χ²=14.135, P=0.0001). Other donor-unrelated factors, like cold ischemia time, also had an impact on EAD (r=0.135, P=0.010), especially in patients with model for end-stage liver disease (MELD) <25 (ß=0.001, P=0.008). ET-DRI was a crucial factor in estimating overall and allograft survival after liver transplantation. CONCLUSIONS The findings from this study support the possibility of liver transplantation using organs obtained by EDC. Other factors, like donor sex and cold ischemic time, are not part of the EDC, although they have an impact on EAD. Organs obtained by EDC continue to be an option to address the organ shortage.

Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is in most transplant regions a contraindication for liver transplantation, even ruling out an active waiting list registration. However, recent studies showed that well-selected patients after a neo-adjuvant treatment benefit from liver transplantation with good long-term outcomes. The role of living donor liver transplantation is unclear for this indication. The current study focuses on LDLT for intrahepatic cholangiocarcinoma.

[Surgical treatment of hepato-pancreatic metastases from renal cell carcinoma]. / Chirurgische Therapie von Leber- und Pankreasmetastasen von Nierenzellkarzinomen.

BACKGROUND: The role of surgical treatment of hepato-pancreatic metastases from renal cell carcinoma is still under discussion. MATERIAL AND METHODS: We report about 52 patients of whom 33 underwent surgery for liver metastases and 19 for pancreatic metastases from 1995 to 2018. RESULTS: The 5­year survival rate of all patients with partial liver resection was statistically significantly lower (38%, median survival time 34 months) than with pancreas resection (69%, median survival time 69 months, p = 0.017). Of the patients 21 survived the resection of metastases longer than 5 years and 4 patients longer than 10 years. In R0 resected patients, recurrences were observed in 13 cases after liver resection and in 9 cases after pancreas resection. The cumulative recurrence rate after 5 years was 38% for the liver and 57% for the pancreas. In R0 partial liver resections, an interval <24 months between nephrectomy and liver resection as well as multiple metastases were negative prognostic factors. CONCLUSION: In spite of high recurrence rates, surgical treatment for hepato-pancreatic metastases from renal cell carcinoma yielded very good long-term results, in particular with complete resection of solitary metachronous metastases. Repeated surgery for completely resectable metastases, resulted in long tumor-free intervals and thus contributed to good long-term results.