Untersuchung chirurgischer Techniken zur Behandlung fortgeschrittener Lebererkrankungen und assoziierter Risikofaktoren

In den folgenden Publikationen wurden folgende Fragestellungen systematisch untersucht: 1. Der Stellenwert der präoperativen Bildgebung für die chirurgische Strategie bei der portosystemischen Shunt-Chirurgie. 2. Die Machbarkeit der Lebertransplantation ohne Kältekonservierung 3. Die Assoziation zwischen der Rekurrenz des hepatozellulären Karzinoms nach Lebertransplantation mit Episoden akuter Abstoßung 4. Der Einfluss der Teil-Leber-Lebendspende auf die Lebensqualität des Spenders und Untersuchung postoperativer Ergebnisse 5. Der Stellenwert eines biologischen Netzes beim Bauchwandverschlusses in mehreren Etappen nach pädiatrischer Lebertransplantation bei Kleinkinder

Outcome after pediatric liver transplantation for staged abdominal wall closure with use of biological mesh—Study with long‐term follow‐up

Abdominal wall closure after pediatric liver transplantation (pLT) in infants may be hampered by graft-to-recipient size discrepancy. Herein, we describe the use of a porcine dermal collagen acellular graft (PDCG) as a biological mesh (BM) for abdominal wall closure in pLT recipients. Patients <2 years of age, who underwent pLT from 2011 to 2014, were analyzed, divided into definite abdominal wall closure with and without implantation of a BM. Primary end-point was the occurrence of postoperative abdominal wall infection. Secondary end-points included 1- and 5-year patient and graft survival and the development of abdominal wall hernia. In five out of 21 pLT recipients (23.8%), direct abdominal wall closure was achieved, whereas 16 recipients (76.2%) received a BM. BM removal was necessary in one patient (6.3%) due to abdominal wall infection, whereas no abdominal wall infection occurred in the no-BM group. No significant differences between the two groups were observed for 1- and 5-year patient and graft survival. Two late abdominal wall hernias were observed in the BM group vs none in the no-BM group. Definite abdominal wall closure with a BM after pLT is feasible and safe when direct closure cannot be achieved with comparable postoperative patient and graft survival rates

Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications

Long-Term Outcome after Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Background and Objectives: Progressive familial intrahepatic cholestasis (PFIC) is a rare autosomal recessive inherited disease divided into five types (PFIC 1-5). Characteristic for all types is early disease onset, which may result clinically in portal hypertension, fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and extrahepatic manifestations. Liver transplantation (LT) is the only successful treatment approach. Our aim is to present the good long-term outcomes after liver transplantation for PFIC1, focusing on liver function as well as the occurrence of extrahepatic manifestation after liver transplantation. Materials and Methods: A total of seven pediatric patients with PFIC1 underwent liver transplantation between January 1999 and September 2019 at the Department of Surgery, Charite Campus Virchow Klinikum and Charite Campus Mitte of Charite-Universitatsmedizin Berlin. Long-term follow-up data were collected on all patients, specifically considering liver function and extrahepatic manifestations. Results: Seven (3.2%) recipients were found from a cohort of 219 pediatric patients. Two of the seven patients had multilocular HCC in cirrhosis. Disease recurrence or graft loss did not occur in any patient. Two patients (male, siblings) had persistently elevated liver parameters but showed excellent liver function. Patient and graft survival during long-term follow-up was 100%, and no severe extrahepatic manifestations requiring hospitalization or surgery occurred. We noted a low complication rate during long-term follow-up and excellent patient outcome. Conclusions: PFIC1 long-term follow-up after LT shows promising results for this rare disease. In particular, the clinical relevance of extrahepatic manifestations seems acceptable, and graft function seems to be barely affected. Further multicenter studies are needed to analyze the clinically inhomogeneous presentation and to better understand the courses after LT

Portosystemic shunt surgery in the era of TIPS: imaging-based planning of the surgical approach

Purpose: With the spread of transjugular intrahepatic portosystemic shunts (TIPS), portosystemic shunt surgery (PSSS) has decreased and leaves more complex patients with great demands for accurate preoperative planning. The aim was to evaluate the role of imaging for predicting the most suitable PSSS approach. Material and methods: Forty-four patients who underwent PSSS (2002 to 2013) were examined by contrast-enhanced CT (n = 33) and/or MRI (n = 15) prior to surgery. Imaging was analyzed independently by two observers (O1 and O2) with different levels of experience (O1 > O2). They recommended two shunting techniques (vessels and anastomotic variant) for each patient and ranked them according to their appropriateness and complexity. Findings were compared with the actually performed shunt procedure and its outcome. Results: The first two choices taken together covered the performed PSSS regarding vessels in 88%/100% (CT/MRI, O1) and 76%/73% (O2); and vessels + anastomosis in 79%/73% (O1) and 67%/60% (O2). The prediction of complex surgical procedures (resection of interposing structures, additional thrombectomy, use of a collateral vessel, and use of a graft interposition) was confirmed in 87%, resulting in 80% sensitivity and 96% specificity. Larger shunt vessel distances were associated with therapy failure (p = 0.030) and a vessel distance of ≥ 20 mm was identified as optimal cutoff, in which a graft interposition was used. There was no significant difference between MRI and CT in predicting the intraoperative decisions (p = 0.294 to 1.000). Conclusion: Preoperative imaging and an experienced radiologist can guide surgeons in PSSS. CT and MRI provide the information necessary to identify technically feasible variants and complicating factors

Two patients with rare mixed adenoneuroendocrine carcinomas of the rectum

Mixed adenoneuroendocrine carcinomas of the gastrointestinal tract are until today poorly understood and thus very challenging for interdisciplinary therapy. We herewith report the first case series of patients with a primary mixed adenoneuroendocrine carcinoma of the rectum. Both cases were initially diagnosed as adenocarcinoma and only secondarily with mixed adenoneuroendocrine carcinoma and had a poor outcome due to a rapid tumor progression and resistance to chemotherapy. A 65-year-old female presented with local tumor recurrence and hepatopulmonary metastasis 1 year after primary surgery for adenocarcinoma of the rectum and consecutive radiochemotherapy regimen. Fluorouracil (5-FU) was followed by bevacizumab- and capecitabine-based chemotherapy but had to be discontinued due to side effects and progressive disease. Progressive local pain syndrome accompanied by recurrent bleeding episodes led to a local tumor-debulking operation. Afterward, mixed adenoneuroendocrine carcinoma as the underlying diagnosis in the final histopathological examination was detected. The patient died 3 months after the operation in the context of a fulminant tumor progress. A 63-year-old male patient underwent neoadjuvant radiochemotherapy and laparoscopic rectum resection. After 5 months, postoperative oxaliplatin/capecitabine-based adjuvant chemotherapy was switched to carboplatin/etopsid due to a progressive polyneuropathy and biopsy-proven pulmonary metastasis. The patient then had to be switched to local radiation of cerebral metastases and Topotecan due to cerebral bleeding episodes but died 18 months after the initial diagnosis. In conclusion of our case series, mixed adenoneuroendocrine carcinomas of the rectum should be considered as a rare but aggressive tumor entity. An early and detailed histopathological diagnosis is required in order to establish an individual interdisciplinary treatment concept

Over 30 Years of Pediatric Liver Transplantation at the Charité—Universitätsmedizin Berlin

Background: Pediatric liver transplantation (LT) is the treatment of choice for children with end-stage liver disease and in certain cases of hepatic malignancies. Due to low case numbers, a technically demanding procedure, the need for highly specialized perioperative intensive care, and immunological, as well as infectious, challenges, the highest level of interdisciplinary cooperation is required. The aim of our study was to analyze short- and long-term outcomes of pediatric LT in our center. Methods: We conducted a retrospective single-center analysis of all liver transplantations in pediatric patients (≤16 years) performed at the Department of Surgery, Charité – Universitätsmedizin Berlin between 1991 and 2021. Three historic cohorts (1991–2004, 2005–2014 and 2015–2021) were defined. Graft- and patient survival, as well as perioperative parameters were analyzed. The study was approved by the institutional ethics board. Results: Over the course of the 30-year study period, 212 pediatric LTs were performed at our center. The median patient age was 2 years (IQR 11 years). Gender was equally distributed (52% female patients). The main indications for liver transplantation were biliary atresia (34%), acute hepatic necrosis (27%) and metabolic diseases (13%). The rate of living donor LT was 25%. The median cold ischemia time for donation after brain death (DBD) LT was 9 h and 33 min (IQR 3 h and 46 min). The overall donor age was 15 years for DBD donors and 32 years for living donors. Overall, respective 1, 5, 10 and 30-year patient and graft survivals were 86%, 82%, 78% and 65%, and 78%, 74%, 69% and 55%. One-year patient survival was 85%, 84% and 93% in the first, second and third cohort, respectively (p = 0.14). The overall re-transplantation rate was 12% (n = 26), with 5 patients (2%) requiring re-transplantation within the first 30 days. Conclusion: The excellent long-term survival over 30 years showcases the effectiveness of liver transplantation in pediatric patients. Despite a decrease in DBD organ donation, patient survival improved, attributed, besides refinements in surgical technique, mainly to improved interdisciplinary collaboration and management of perioperative complications

Serum Selenium Status as a Diagnostic Marker for the Prognosis of Liver Transplantation

The trace element selenium (Se) is taken up from the diet and is metabolized mainly by hepatocytes. Selenoprotein P (SELENOP) constitutes the liver-derived Se transporter. Biosynthesis of extracellular glutathione peroxidase (GPx3) in kidney depends on SELENOP-mediated Se supply. We hypothesized that peri-operative Se status may serve as a useful prognostic marker for the outcome in patients undergoing liver transplantation due to hepatocellular carcinoma. Serum samples from liver cancer patients were routinely collected before and after transplantation. Concentrations of serum SELENOP and total Se as well as GPx3 activity were determined by standardized tests and related to survival, etiology of cirrhosis/carcinoma, preoperative neutrophiles, lymphocytes, thyrotropin (TSH) and Child-Pugh and Model for End-Stage Liver Disease (MELD) scores. A total of 221 serum samples from 79 transplanted patients were available for analysis. The Se and SELENOP concentrations were on average below the reference ranges of healthy subjects. Patients with ethanol toxicity-dependent etiology showed particularly low SELENOP and Se concentrations and GPx3 activity. Longitudinal analysis indicated declining Se concentrations in non-survivors. We conclude that severe liver disease necessitating organ replacement is characterized by a pronounced Se deficit before, during and after transplantation. A recovering Se status after surgery is associated with positive prognosis, and an adjuvant Se supplementation may, thus, support convalescence

Minimization of Immunosuppressive Therapy Is Associated with Improved Survival of Liver Transplant Patients with Recurrent Hepatocellular Carcinoma

Introduction: Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown. Methods: All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed. Results: Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0–203.0), with the majority presenting early after transplantation (63.0%, &lt;2 years). Median survival after rHCC diagnosis was 10.6 months (0.3–228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (n = 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months). Conclusion: Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful