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

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Hepatobiliary & Pancreatic Diseases International 2019年第3期18卷 228-236页

作者： Sophia Schmitz Georg Lurje Florian Ulmer Anne Andert Philipp Bruners Maximilian Schulze-Hagen ulf neumann Wenzel Schoening Department of General- Visceral- and Transplantation Surgery University Hospital of RWTH Aachen Aachen Germany Department of Diagnostic and Interventional Radiology University Hospital of RWTH Aachen Aachen Germany Department of Surgery Maastricht University Medical Center (MUMC) Maastricht Netherlands Department of Surgery Charité– University Medicine at Berlin Germany

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

关键词： Hepatocellular carcinoma Liver transplantation Therapeutic embolization Liver neoplasms Organ transplantation

Comparative study of the effects of terlipressin versus splenectomy on liver regeneration after partial hepatectomy in rats

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Hepatobiliary & Pancreatic Diseases International 2017年第5期16卷 506-511页

作者： Tom Florian Ulmer Anne Weiland Georg Lurje Christian Klink Anne Andert Hamid Alizai Christoph Heidenhain ulf neumann Department of General Visceral and Transplantation Surgery RWTH Aachen University Hospital Aachen Germany Department of Urology Helios Hospital Berlin-Buch Germany

BACKGROUND: Post-hepatectomy liver failure as a result of insufficient liver remnant is a feared complication in liver surgery. Efforts have been made to find new strategies to support liver regeneration. The aim of this study was to investigate the effects of terlipressin versus splenectomy on postoperative liver function and liver regeneration in rats undergoing 70%partial hepatectomy. METHODS: Seventy-two male Wistar rats were randomly assigned into three groups(n=24 in each group): 70% partial hepatectomy as control(PHC), 70% partial hepatectomy with splenectomy(PHS) or 70% partial hepatectomy with a micropump for terlipressin administration(PHT). Eight rats in each group were sacrificed on postoperative day(POD) 1,3 and 7. To assess liver regeneration, immunohistochemical analysis of liver tissue using bromodeoxyuridine(BrdU) and Ki-67 labeling was performed. Portal venous pressure, serum concentrations of creatinine, urea, albumin, bilirubin and prothrombin time as well as liver-, body-weight and their ratio were determined on POD 1, 3 and ***: The liver-, body-weight and their ratio were not statistically different among the groups. On POD 1, 3 and 7 portal venous pressure in the intervention groups(PHT:8.13 ±1.55, 10.38±1.30, 6.25±0.89 cm H2O and PHS: 7.50±0.93,8.88 ±2.42, 5.75±1.04 cm H2O) was lower compared to the control group(PHC: 8.63±2.06, 10.50±2.45, 6.50±2.67 cmH2O). Hepatocyte proliferation in the intervention groups was delayed, especially after splenectomy on POD 1(Brd U: PHS vs PHC, 20.85% ±13.05% vs 28.11%±10.10%; Ki-67, 20.14%±14.10% vs 23.96% ±11.69%). However, none of the differences were statistically ***: Neither the administration of terlipressin nor splenectomy improved liver regeneration after 70% partial hepatectomy in rats. Further studies assessing the regulation of portal venous pressure as well as extended hepatectomy animal models and liver function tests will help to further investigate mechanisms of live

关键词： liver regeneration liver failure terlipressin splenectomy hepatectomy

Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1632-1647页

作者： Katharina Joechle Jessica Guenzle Claus Hellerbrand Pavel Strnad Thorsten Cramer ulf Peter neumann Sven Arke Lang Visceral and Transplantation Surgery University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany Department of General and Visceral Surgery Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburg 79106Germany Institute of Biochemistry Friedrich-Alexander University Erlangen-NurnbergErlangen 91054Germany Department of Internal Medicine Ⅲ University Hospital Rheinisch-Westfalisch Technische Hochschule AachenAachen 52074Germany

The mammalian target of rapamycin(mTOR)acts in two structurally and functionally distinct protein complexes,mTOR complex 1(mTORC1)and mTOR complex 2(mTORC2).Upon deregulation,activated mTOR signaling is associated with multiple processes involved in tumor growth and *** with mTORC1,much less is known about mTORC2 in cancer,mainly because of the unavailability of a selective ***,existing data suggest that mTORC2 with its two distinct subunits Rictor and mSin1 might play a more important role than assumed so *** is one of the key effectors of the PI3K/AKT/mTOR pathway and stimulates cell growth,cell survival,metabolism,and cytoskeletal *** is not only implicated in tumor progression,metastasis,and the tumor microenvironment but also in resistance to ***,the central subunit of mTORC2,was found to be upregulated in different kinds of cancers and is associated with advanced tumor stages and a bad ***,AKT,the main downstream regulator of mTORC2/Rictor,is one of the most highly activated proteins in *** and secondary liver cancer are major problems for current cancer therapy due to the lack of specific medical treatment,emphasizing the need for further therapeutic *** review,therefore,summarizes the role of mTORC2/Rictor in cancer,with special focus on primary liver cancer but also on liver metastases.

关键词： Mammalian target of rapamycin Mammalian target of rapamycin complex 2 Rictor Liver cancer Liver metastases Hepatocellular carcinoma Cholangiocellular carcinoma

Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2017年第6期16卷 617-623页

作者： Anne Andert Tom Florian Ulmer Wenzel Schoning Daniela Kroy Marc Hein Patrick Hamid Alizai Christoph Heidenhain ulf neumann Maximilian Schmeding Department of General Visceral and Transplant SurgeryUniklinik RWTH Aachen AachenGermany Department of Internal Medicine Uniklinik RWTH Aachen AachenGermany Department of Anaesthesiology Uniklinik RWTH Aachen AachenGermany Department of General and Visceral Surgery Sana Hospital Düsseldorf-Gerresheim Germany

BACKGROUND:The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver ***:Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis(MiS):MiS 60%(n=26).The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction(EAD) and primary nonfunction(PNF). RESULTS:The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF,one occurred in the MiS 60% ***:Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

关键词： liver transplantation liver steatosis microvesicular steatosis early allograft dysfunction

Impact of body composition on survival and morbidity after liver resection in hepatocellular carcinoma patients

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Hepatobiliary & Pancreatic Diseases International 2019年第1期18卷 28-37页

作者： Andreas Kroh Diane Uschner Toine Lodewick Roman M Eickhoff Wenzel Sch?ning Florian T Ulmer ulf P neumann Marcel Binneb?sel Department of General Visceral and Transplant Surgery University Hospital RWTH Aachen Institute of Medical Statistics University Hospital RWTH Aachen Department of Surgery Maastricht University Medical Center Department of Radiology Zuyderland Medical Centre Department of Radiology Maastricht University Medical Centre

Background: Hepatocellular carcinoma is the most common innate liver tumor. Due to improved surgical techniques, even extended resections are feasible, and more patients can be treated with curative intent. As the liver is the central metabolic organ, preoperative metabolic assessment is crucial for risk stratification. Sarcopenia, obesity and sarcopenic obesity characterize body composition and metabolic status. Here we present the impact of body composition on survival after liver resection in patients with hepatocellular carcinoma. Methods: A retrospective database analysis of 70 patients who were assigned for liver resection due to hepatocellular carcinoma was conducted. For assessment of sarcopenia and obesity, skeletal muscle surface area was measured at lumbar vertebra 3 level(L3) in preoperative four-phase contrast enhanced abdominal CT scans, and L3 muscle index and body fat percentage were calculated. Results: Univariate analysis comparing the survival curves using the score test demonstrated superior postoperative overall survival for sarcopenic( P = 0.035) and sarcopenic obese( P = 0.048) patients as well as a trend favoring obese( P = 0.130) subjects. Whereas multivariate analysis could not identify significant difference in postoperative survival regarding sarcopenia, obesity or sarcopenic obesity. Only large tumor size, multifocal disease and male gender were risk factors for long-term survival. Conclusions: Sarcopenia, obesity and sarcopenic obesity are indeed no risk factors for poor postoperative survival in this study. Our data do not support the evaluation of sarcopenia, obesity and sarcopenic obesity before liver resection in hepatocellular carcinoma patients.

关键词： Hepatocellular carcinoma Sarcopenia Obesity Sarcopenic obesity Liver resection

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

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World Journal of Gastrointestinal Surgery 2021年第1期13卷 19-29页

作者： Daniel Heise Jan Bednarsch Andreas Kroh Sandra Schipper Roman Eickhoff Marielle Coolsen Ronald Van Dam Sven Lang ulf neumann Florian Ulmer Department of Surgery and Transplantation University Hospital RWTH AachenAachen 52074Germany Department of Surgery Maastricht University Medical CenterMaastricht 6229 HXNetherlands

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

关键词： Laparoscopic hepatectomy Obesity Overweight Morbidity Postoperative outcome Cost

Biliary complications in liver transplantation: Impact of anastomotic technique and ischemic time on short- and long-term outcome

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World Journal of Transplantation 2015年第4期5卷 300-309页

作者： Stefan Kienlein Wenzel Schoening Anne Andert Daniela Kroy ulf Peter neumann Maximilian Schmeding Department of General Visceral and Transplantation SurgeryUniversity Hospital Aachen Department of Gastroenterology and Hepatology University Hospital Aachen

AIM: To elucidate the impact of various donor recipient and transplant factors on the development of biliary complications after liver ***: We retrospectively reviewed 200 patients of our newly established liver transplantation(LT) program, who received full size liver graft. Biliary reconstruction was performed by side-to-side(SS), end-to-end(EE) anastomosis or hepeaticojejunostomy(HJ). Biliary complications(BC), anastomotic stenosis, bile leak, papillary stenosis, biliary drain complication, ischemic type biliary lesion(ITBL) were evaluated by studying patient records, corresponding radiologic imaging and reports of interventional procedures [e.g., endoscopic retrograde cholangiopancreatography(ERCP)]. Laboratory results included alanine aminotransferase(ALT), gammaglutamyltransferase and direct/indirect bilirubin with focus on the first and fifth postoperative day, six weeks after LT. The routinely employed external bile drain was examined by a routine cholangiography on the fifth postoperative day and six weeks after transplantation as a standard procedure, but also whenever clinically indicated. If necessary, interventional(e.g., ERCP) or surgical therapy was performed. In case of biliary complication, patients were selected, assigned to different complication-groups and subsequently reviewed in detail. To evaluate the patients outcome, we focussed on appearance of postoperative/post-interventional cholangitis, need for rehospitalisation, retransplantation, ITBL or death caused by ***: A total of 200 patients [age: 56(19-72), alcoholic cirrhosis: n = 64(32%), hepatocellular carcinoma: n = 40(20%), acute liver failure: n = 23(11.5%), cryptogenic cirrhosis: n = 22(11%), hepatitis B virus /hepatitis C virus cirrhosis: n = 13(6.5%), primary sclerosing cholangitis: n = 13(6.5%), others: n = 25(12.5%) were included. The median follow-up was 27 mo until June 2015. The overall biliary complication rate was 37.5%(n = 75) with anastomotic stric

关键词： Liver transplantation Biliary complications Anastomotic stenosis Ischemic type biliary lesion Nonanastomotic strictures Bile leak Ischemic time Biliary drain complications

Extended surgical resection for xanthogranulomatous cholecystitis mimicking advanced gallbladder carcinoma: A case report and review of literature

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World Journal of Gastroenterology 2006年第14期12卷 2293-2296页

作者： Antonino Spinelli Guido Schumacher Andreas Pascher Enrique Lopez-Hanninen Hussain Al-Abadi Christoph Benckert Igor M Sauer Johann Pratschke ulf P neumann Sven Jonas Jan M Langrehr Peter Neuhaus Department of General Visceral and Transplantation Surgery Charitè-Universitatsmedizin BerlinCampus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany Department of Radiology Charitè-Universitatsmedizin Berlin Campus Virchow KlinikumAugustenburger Platz 113353 BerlinGermany

Xanthogranulomatous cholecystitis （XGC） is a destructive inflammatory disease of the gallbladder, rarely involving adjacent organs and mimicking an advanced gallbladder carcinoma. The diagnosis is usually possible only after pathological examination. A 46 year-old woman was referred to our center for suspected gallbladder cancer involving the liver hilum, right liver lobe, right colonic flexure, and duodenum. Brushing cytology obtained by endoscopic retrograde cholangiography （ERC） showed high-grade dysplasia. The patient underwent an en-bloc resection of the mass, consisting of right Iobectomy, right hemicolectomy, and a partial duodenal resection. Pathological examination unexpectedly revealed an XGC. Only six cases of extended surgical resections for XGC with direct involvement of adjacent organs have been reported so far. In these cases, given the possible coexistence of XGC with carcinoma, malignancy cannot be excluded, even after cytology and intraoperative frozen section investigation. In conclusion, due to the poor prognosis of gallbladder carcinoma on one side and possible complications deriving from highly aggressive inflammatory invasion of surrounding organs on the other side, it seems these cases should be treated as malignant tumors until proven otherwise. Clinicians should include XGC among the possible differential diagnoses of masses in liver hilum.

关键词： Xanthogranulomatous cholecystitis Gallbladder cancer Gallbladder carcinoma

Liver transplantation in malignant disease

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World Journal of Clinical Oncology 2021年第8期12卷 623-645页

作者： Sven Arke Lang Jan Bednarsch Zoltan Czigany Katharina Joechle Andreas Kroh Iakovos Amygdalos Pavel Strnad Tony Bruns Daniel Heise Florian Ulmer ulf Peter neumann Department of Surgery and Transplantation University Hospital RWTH AachenAachen 52074Germany Department of Internal Medicine III University Hospital RWTH AachenAachen 52074Germany

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

关键词： Liver transplantation Hepatocellular carcinoma Cholangiocellular carcinoma Hepatic epithelioid hemangioendothelioma Undifferentiated embryonal sarcoma of the liver Colorectal cancer liver metastases Neuroendocrine cancer liver metastases