1
|
Bahrami P, Al Zein M, Eid AH, Sahebkar A. Liver Transplantation for Non-hepatocellular Carcinoma: The Role of Immune Checkpoint Inhibitors. J Clin Exp Hepatol 2025; 15:102558. [PMID: 40303874 PMCID: PMC12036051 DOI: 10.1016/j.jceh.2025.102558] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 03/22/2025] [Indexed: 05/02/2025] Open
Abstract
Colorectal cancer (CRC), gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), and cholangiocarcinoma (CCA) exhibit high rates of morbidity and mortality once metastasized to the liver. Liver transplantation (LT) is a viable therapeutic approach for these cancers in highly selected patients; however, their invasive nature at late stages causes many patients to be delisted from transplantation or to require further downstaging. Immunotherapy with immune checkpoint modulators has revolutionized cancer research. Immune checkpoint inhibitors (ICI) leverage the chronic inflammatory state and the overexpression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) by malignant cells and regulatory T cells, to block immune checkpoints and counteract tumor's ability to evade the immune system. However, the interaction between allograft PD-L1 and PD-1 on infiltrating T cells functions as a means of graft tolerance in cases of LT. Therefore, the application of ICIs might block this protective effect and induce graft rejection, a phenomenon particularly observed in PD-1/PD-L1 inhibiting ICIs. The risk of post-LT graft rejection can be mitigated by applying advanced biomarkers and specifying certain mutations that enhance patient selection criteria for pre-LT ICI use. Furthermore, the determination of optimal intervals of ICI administration pre- and post-LT, identification of ICI indications in de novo malignancies occurring after LT, and investigation of biomarkers for early rejection detection, pave the way for more promising LT outcomes in patients with CRC, GEP-NEN, or CCA. Therefore, this review aims to illustrate a comprehensive overview of the role of ICI therapy in the management of non-hepatocellular carcinoma transplant oncology cancers by demonstrating the potential for its application in both pre-and post-LT states, and pathways to reduce or timely detect ICI-associated graft rejection.
Collapse
Affiliation(s)
- Pegah Bahrami
- Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Al Zein
- Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon
| | - Ali H. Eid
- Department of Basic Medical Sciences, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Centre for Research Impact and Outcome, Chitkara University, Rajpura 140417, Punjab, India
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| |
Collapse
|
2
|
Dasari BVM, Line PD, Sapisochin G, Hibi T, Bhangui P, Halazun KJ, Shetty S, Shah T, Magyar CTJ, Donnelly C, Chatterjee D. Liver transplantation as a treatment for cancer: comprehensive review. BJS Open 2025; 9:zraf034. [PMID: 40380811 PMCID: PMC12084677 DOI: 10.1093/bjsopen/zraf034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 01/30/2025] [Accepted: 02/07/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Liver transplantation for cancer indications has gained momentum in recent years. This review is intended to optimize the care setting of liver transplant candidates by highlighting current indications, technical aspects and barriers with available solutions to facilitate the guidance of available strategies for healthcare professionals in specialized centres. METHODS A review of the most recent relevant literature was conducted for all the cancer indications of liver transplantation including colorectal cancer liver metastases, hilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, neuroendocrine tumours, hepatocellular carcinoma and hepatic epitheloid haemangioendothelioma. RESULTS Transplant benefit from the best available evidence, including SECA I, SECA II, TRANSMET studies for colorectal liver metastases, various preoperative protocols for cholangiocarcinoma patients, standard, extended selection criteria for hepatocellular carcinoma and neuroendocrine tumours, are discussed. Innovative approaches to deal with organ shortages, including machine-perfused deceased grafts, living donor liver transplantation and RAPID procedures, are also explored. CONCLUSION Cancer indications for liver transplantation are here to stay, and the selection criteria among all cancer groups are likely to evolve further with improved prognostication of tumour biology using adjuncts such as radiomics, cancer genomics, and circulating DNA and RNA status. International prospective registry-based studies could overcome the limitations of smaller patient cohorts and lack of level 1 evidence.
Collapse
Affiliation(s)
- Bobby V M Dasari
- Department of Liver Transplantation and HBP Surgery, Queen Elizabeth Hospital, Birmingham, UK
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
| | - Pal-Dag Line
- Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway
| | - Gonzalo Sapisochin
- Department of Surgery, Multi-Organ Transplant Program, University Health Network, Toronto, Canada
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Prashant Bhangui
- Liver Transplantation and Hepatobiliary Surgery, Medanta Institute of Liver Transplantation and Regenerative Medicine, Medanta-The Medicity, Gurgaon (Delhi NCR), India
| | - Karim J Halazun
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Shishir Shetty
- Department of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, Birmingham, UK
| | - Christian T J Magyar
- Department of Abdominal Transplant & HBP Surgical Oncology, Toronto General Hospital, University Health Network, University of Toronto, Toronto, Canada
| | - Conor Donnelly
- Department of Liver Transplantation and Hepatobiliary Surgery, NYU Grossman School of Medicine, NYU Langone Health, New York, USA
| | - Dev Chatterjee
- BRC Clinical Fellow Liver Medicine, University Hospitals of Birmingham, Birmingham, UK
| |
Collapse
|
3
|
Li L, Hirukawa K, Morinaga J, Goto T, Isono K, Honda M, Sugawara Y, Hibi T. Extreme surgery using the hypothermic perfusion technique for conventionally unresectable abdominal malignant tumours: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109692. [PMID: 40010010 DOI: 10.1016/j.ejso.2025.109692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2024] [Revised: 01/26/2025] [Accepted: 02/10/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Extreme surgery using the hypothermic perfusion technique is often the only treatment option to achieve R0 resection and long-term prognosis for abdominal tumours that are either conventionally unresectable or contraindicated to allotransplantation. We conducted a systematic review and meta-analysis to delineate the indications and outcomes of extreme surgery. MATERIALS AND METHODS Human studies on extreme resection for abdominal malignant tumours were searched among five databases between January 1988 to March 2023. The Risk Of Bias In Non-randomised Studies - of Interventions tool was used to assess the risk of bias. A meta-analysis of proportions was performed, pooling 1-, 3- and 5-year overall survival and recurrence rates. RESULTS This study comprised 73 studies encompassing 333 patients who underwent extreme liver resection (in situ, n = 127; ante situm, n = 72; ex situ, n = 134). Additionally, 90 patients from 17 studies focusing on extreme resection of other (non-hepatic) organs were included. The pooled 90-day mortality and 1- and 5-year overall survival rates were 7.3 %, 72.3 % and 23.4 %, respectively. The 1- and 5-year recurrence rates were 38.7 % and 86.1 %, respectively. Patients aged <65 years had a significantly lower 90-day mortality (5.5 % vs. 29.6 %; P = 0.022) and a higher 5-year overall survival rate (23.9 % vs. 0 %; P < 0.001) than those aged ≥65 years. Additionally, non-epithelial tumours were associated with favourable prognosis compared with epithelial tumours. CONCLUSION Extreme surgery offers acceptable outcomes for younger patients with non-epithelial tumours that are either unresectable by conventional cancer surgery or contraindicated to allotransplantation.
Collapse
Affiliation(s)
- Lianbo Li
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; Department of Pediatric Surgery, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Sichuan, China
| | - Kazuya Hirukawa
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Jun Morinaga
- Department of Clinical Investigation, Kumamoto University Hospital, Kumamoto, Japan
| | - Toru Goto
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Kaori Isono
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Masaki Honda
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Yasuhiko Sugawara
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan
| | - Taizo Hibi
- Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
| |
Collapse
|
4
|
Marzioni M, Maroni L, Aabakken L, Carpino G, Groot Koerkamp B, Heimbach J, Khan S, Lamarca A, Saborowski A, Vilgrain V, Nault JC. EASL Clinical Practice Guidelines on the management of extrahepatic cholangiocarcinoma. J Hepatol 2025:S0168-8278(25)00162-X. [PMID: 40348685 DOI: 10.1016/j.jhep.2025.03.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2025] [Accepted: 03/12/2025] [Indexed: 05/14/2025]
Abstract
Recent years have witnessed significant advances in the imaging, molecular profiling, and systemic treatment of cholangiocarcinoma (CCA). Despite this progress, the early detection, precise classification, and effective management of CCA remain challenging. Owing to recent developments and the significant differences in CCA subtypes, EASL commissioned a panel of experts to draft evidence-based recommendations on the management of extrahepatic CCA, comprising distal and perihilar CCA. Particular attention is given to the need for accurate classification systems, the integration of emerging molecular insights, and practical strategies for diagnosis and treatment that reflect real-world clinical scenarios.
Collapse
|
5
|
Ito T, Taura K, Fukumitsu K, Okumura S, Ogiso S, Anazawa T, Nagai K, Uchida Y, Ishii T, Hatano E. Safety and efficacy of living donor liver transplantation for unresectable perihilar cholangiocarcinoma: A single center prospective study. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2025; 32:276-286. [PMID: 39996522 PMCID: PMC12038382 DOI: 10.1002/jhbp.12121] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/26/2025]
Abstract
BACKGROUND The prognosis for unresectable perihilar cholangiocarcinoma (phCCA) is extremely poor. Liver transplantation in combination with neoadjuvant chemoradiation therapy has become the treatment of choice for unresectable phCCA in the USA. In 2018, we launched a prospective study to evaluate the safety and efficacy of living donor liver transplantation (LDLT) for unresectable phCCA. METHODS A total of 10 patients were enrolled in this study between 2018 and 2024. Finally, five patients with unresectable phCCA underwent LDLT after neoadjuvant chemotherapy, radiation, and staging laparotomy, while the other five patients dropped out of the protocol. RESULTS The median follow-up period was 23.7 months. The overall survival rate for the five patients who underwent LDLT was 100% after one year. Hepatic artery thrombosis and delayed gastric emptying occurred in two and three cases, respectively. The histological efficacy of preoperative treatment was grade IIb and III, according to the Evans classification, in all five patients. All surgical margins and dissected lymph nodes were negative. Four patients were alive with no evidence of disease recurrence while one patient had recurrence 10 months after LDLT. CONCLUSIONS LDLT is feasible and may be a last-resort treatment option for unresectable phCCA, although the long-term outcomes need to be carefully monitored. CLINICAL TRIAL REGISTER AND CLINICAL REGISTRATION NUMBER The UMIN registration number for this study is 000033348.
Collapse
Affiliation(s)
- Takashi Ito
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kojiro Taura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of Gastroenterological Surgery and OncologyMedical Research Institute, Kitano HospitalOsakaJapan
| | - Ken Fukumitsu
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
- Department of SurgeryGastrointestinal Center, Kyoto Katsura HospitalKyotoJapan
| | - Shinya Okumura
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Satoshi Ogiso
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takayuki Anazawa
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Kazuyuki Nagai
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Yoichiro Uchida
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Takamichi Ishii
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| | - Etsuro Hatano
- Department of Surgery, Graduate School of MedicineKyoto UniversityKyotoJapan
| |
Collapse
|
6
|
van Hootegem SJM, van der Linde M, Schneider MA, Kim J, Berlth F, Sugita Y, Grimminger PP, Baiocchi GL, De Manzoni G, Bencivenga M, Gisbertz S, Nunobe S, Yang HK, Gutschow CA, Lagarde SM, Lingsma HF, Wijnhoven BPL. Impact of postoperative complications on clinical outcomes after gastrectomy for cancer: multicentre study. Br J Surg 2025; 112:znaf043. [PMID: 40156166 PMCID: PMC11953074 DOI: 10.1093/bjs/znaf043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 12/18/2024] [Accepted: 02/04/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND To reduce the clinical and economic burden of complications after gastrectomy for gastric cancer, specific complications should be targeted to effectively allocate healthcare resources for quality improvement and preventive measures. The aim of this study was to assess the impact of complications on clinical outcomes. METHODS This was a retrospective multicentre study of patients who underwent (sub)total gastrectomy for gastric or junctional adenocarcinoma at 43 centres in 16 countries between 2017 and 2021. Outcomes were escalation of care, reoperation, prolonged hospital stay (greater than the 75th percentile), readmission, and 30-day mortality. Adjusted relative risks and population attributable fractions were estimated for specific complication-outcome pairs. The population attributable fraction represents the percentage reduction in the frequency of an adverse outcome if a complication could be completely prevented in the population. RESULTS In total, 7829 patients were included. Postoperative complications occurred in 1884 patients (24.1%). The most frequent complications were pulmonary complications (436 patients (5.6%)), anastomotic leakage (363 patients (4.6%)), and abdominal collection (301 patients (3.8%)). Anastomotic leakage, cardiac complications, and pulmonary complications had the greatest impact on 30-day mortality (population attributable fraction 26.6% (95% c.i. 14.5% to 38.6%), 18.7% (95% c.i. 9.4% to 28.0%), and 15.6% (95% c.i. 12.0% to 30.0%) respectively). Anastomotic leakage and pulmonary complications had the greatest impact on escalation of care (population attributable fraction 26.3% (95% c.i. 20.6% to 32.0%) and 18.4% (95% c.i. 11.7% to 25.2%) respectively), whereas anastomotic leakage and intra-abdominal bleeding had the greatest impact on reoperation (population attributable fraction 31.6% (95% c.i. 26.4% to 36.9%) and 8.5% (95% c.i. 5.5% to 11.5%) respectively). Most of the studied complications contributed to a prolonged hospital stay, whereas the contribution of complications to readmission did not exceed 15.9%. Subgroup analysis showed regional variation in the impact of complications. CONCLUSION Anastomotic leakage had the largest overall negative impact on clinical outcomes after gastrectomy for gastric adenocarcinoma. Reducing the incidence of anastomotic leakage and pulmonary complications would have the most impact on the burden of complications.
Collapse
Affiliation(s)
| | | | - Marcel A Schneider
- Department of Surgery & Transplantation, University Hospital Zürich, Zürich, Switzerland
| | - Jeesun Kim
- Department of Surgery, Seoul National University Cancer Hospital, Seoul, Korea
| | - Felix Berlth
- Department of General, Visceral and Transplant Surgery, University Medical Centre Mainz, Mainz, Germany
- Department of Surgery, University Hospital of Tuebingen, Tuebingen, Germany
| | - Yutaka Sugita
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Peter P Grimminger
- Department of General, Visceral and Transplant Surgery, University Medical Centre Mainz, Mainz, Germany
| | | | | | - Maria Bencivenga
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | - Suzanne Gisbertz
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
- Cancer Centre Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, The Netherlands
| | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University Cancer Hospital, Seoul, Korea
| | - Christian A Gutschow
- Department of Surgery & Transplantation, University Hospital Zürich, Zürich, Switzerland
| | - Sjoerd M Lagarde
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Hester F Lingsma
- Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands
| | - Bas P L Wijnhoven
- Department of Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands
| |
Collapse
|
7
|
Malik AK, Davidson BR, Manas DM. Surgical management, including the role of transplantation, for intrahepatic and peri-hilar cholangiocarcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:108248. [PMID: 38467524 DOI: 10.1016/j.ejso.2024.108248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Revised: 02/28/2024] [Accepted: 03/03/2024] [Indexed: 03/13/2024]
Abstract
Intrahepatic and peri-hilar cholangiocarcinoma are life threatening disease with poor outcomes despite optimal treatment currently available (5-year overall survival following resection 20-35%, and <10% cured at 10-years post resection). The insidious onset makes diagnosis difficult, the majority do not have a resection option and the high recurrence rate post-resection suggests that occult metastatic disease is frequently present. Advances in perioperative management, such as ipsilateral portal vein (and hepatic vein) embolisation methods to increase the future liver remnant volume, genomic profiling, and (neo)adjuvant therapies demonstrate great potential in improving outcomes. However multiple areas of controversy exist. Surgical resection rate and outcomes vary between centres with no global consensus on how 'resectable' disease is defined - molecular profiling and genomic analysis could potentially identify patients unlikely to benefit from resection or likely to benefit from targeted therapies. FDG-PET scanning has also improved the ability to detect metastatic disease preoperatively and avoid futile resection. However tumours frequently invade major vasculo-biliary structures, with resection and reconstruction associated with significant morbidity and mortality even in specialist centres. Liver transplantation has been investigated for very selected patients for the last decade and yet the selection algorithm, surgical approach and both value of both neoadjuvant and adjuvant therapies remain to be clarified. In this review, we discuss the contemporary management of intrahepatic and peri-hilar cholangiocarcinoma.
Collapse
Affiliation(s)
- Abdullah K Malik
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; NIHR Blood and Transplant Research Unit, Newcastle University and Cambridge University, Newcastle Upon Tyne, UK.
| | - Brian R Davidson
- Department of HPB and Liver Transplant Surgery, Royal Free Hospital, Royal Free London NHS Foundation Trust, London, UK; Division of Surgery and Interventional Sciences, University College London, London, UK
| | - Derek M Manas
- Department of HPB and Transplant Surgery, Freeman Hospital, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle Upon Tyne, UK; NIHR Blood and Transplant Research Unit, Newcastle University and Cambridge University, Newcastle Upon Tyne, UK; NHS Blood and Transplant, Bristol, UK
| |
Collapse
|
8
|
Harrison JM, Visser BC. Cholangiocarcinoma. Surg Clin North Am 2024; 104:1281-1293. [PMID: 39448128 DOI: 10.1016/j.suc.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2024]
Abstract
Management of intrahepatic cholangiocarcinoma relies on a thorough understanding of the tumor's location and proximity to critical vasculobiliary structures. Mid-common bile duct tumors may require hemihepatectomy or pancreatoduodenectomy based on the status of the intraoperative frozen section. Distal common bile tumors are treated with pancreatoduodenectomy. When appropriate, volumetric assessment of the remnant liver should be performed to identify cases requiring preoperative liver augmentation strategies. A similar strategy should be employed for perihilar tumors, which require a right trisegmentectomy with bilioenteric reconstruction to achieve a negative margin. Adjuvant systemic therapy is recommended and increasing usage of neoadjuvant treatment is being incorporated into borderline resectable or regionally advanced cases.
Collapse
Affiliation(s)
- Jon M Harrison
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA
| | - Brendan C Visser
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, Shanford Univeristy Hospital, 300 Pasteur Drive, H3680, Stanford, CA 94305-5655, USA.
| |
Collapse
|
9
|
Lopez-Lopez V, Morise Z, Gomez Gavara C, Gero D, Abu Hilal M, Goh BK, Herman P, Clavien PA, Robles-Campos R, Wakabayashi G. Global Outcomes Benchmarks in Laparoscopic Liver Surgery for Segments 7 and 8: International Multicenter Analysis. J Am Coll Surg 2024; 239:375-386. [PMID: 38661176 DOI: 10.1097/xcs.0000000000001100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
BACKGROUND In recent years, there has been growing interest in laparoscopic liver resection (LLR) and the audit of the results of surgical procedures. The aim of this study was to define reference values for LLR in segments 7 and 8. STUDY DESIGN Data on LLR in segments 7 and 8 between January 2000 and December 2020 were collected from 19 expert centers. Reference cases were defined as no previous hepatectomy, American Society of Anesthesiologists score less than 3, BMI less than 35 kg/m 2 , no chronic kidney disease, no cirrhosis and portal hypertension, no COPD (forced expiratory volume 1 <80%), and no cardiac disease. Reference values were obtained from the 75th percentile of the medians of all reference centers. RESULTS Of 585 patients, 461 (78.8%) met the reference criteria. The overall complication rate was 27.5% (6% were Clavien-Dindo 3a or more) with a mean Comprehensive Complication Index of 7.5 ± 16.5. At 90-day follow-up, the reference values for overall complication were 31%, Clavien-Dindo 3a or more was 7.4%, conversion was 4.4%, hospital stay was less than 6 days, and readmission rate was <8.33%. Patients from Eastern centers categorized as low risk had a lower rate of overall complication (20.9% vs 31.2%, p = 0.01) with similar Clavien-Dindo 3a or more (5.5% and 4.8%, p = 0.83) compared with patients from Western centers, respectively. CONCLUSIONS This study shows the need to establish standards for the postoperative outcomes in LLR based on the complexity of the resection and the location of the lesions.
Collapse
Affiliation(s)
- Victor Lopez-Lopez
- From the Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de La Arrixaca, IMIB-ARRIXACA, Murcia, Spain (Lopez-Lopez, Robles-Campos)
| | - Zeniche Morise
- Department of Surgery, Fujita Health University School of Medicine Okazaki Medical Center, Okazaki, Aichi, Japan (Morise)
| | - Concepción Gomez Gavara
- Department of HPB Surgery and Transplants, Vall d'Hebron University Hospital, Barcelona Autonomic University, Barcelona, Spain (Gomez Gavara)
| | - Daniel Gero
- Department of Surgery and Transplantation, University Hospital Zurich and University of Zurich, Switzerland (Gero)
| | - Mohammed Abu Hilal
- Department of Surgery, Fondazione Poliambulanza Istituto Ospedaliero, Brescia, Italy (Abu Hilal)
- Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, UK (Abu Hilal)
| | - Brian Kp Goh
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital and National Cancer Center Singapore, Singapore (Goh)
- Surgery Academic Clinical Programme, Duke-National University of Singapore Medical School, Singapore (Goh)
| | - Paulo Herman
- Serviço de Cirurgia do Fígado, Divisão de Cirurgia do Aparelho Digestivo, Departamento de Gastroenterologia, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil (Herman)
| | | | - Ricardo Robles-Campos
- From the Department of General, Visceral and Transplantation Surgery, Clinic and University Hospital Virgen de La Arrixaca, IMIB-ARRIXACA, Murcia, Spain (Lopez-Lopez, Robles-Campos)
| | - Go Wakabayashi
- Department of Surgery, Ageo Central General Hospital, Ageo, Japan (Wakabayashi)
| |
Collapse
|
10
|
Ortiz V, Loeuillard E. Rethinking Immune Check Point Inhibitors Use in Liver Transplantation: Implications and Resistance. Cell Mol Gastroenterol Hepatol 2024; 19:101407. [PMID: 39326581 PMCID: PMC11609388 DOI: 10.1016/j.jcmgh.2024.101407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Revised: 09/18/2024] [Accepted: 09/18/2024] [Indexed: 09/28/2024]
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, including the two most common liver tumors, hepatocellular carcinoma and cholangiocarcinoma, but their use in the peri-transplantation period is controversial. ICI therapy aims to heighten cytotoxic T lymphocytes response against tumors. However, tumor recurrence is common owing to tumor immune response escape involving ablation of CTL response by interfering with antigen presentation, triggering CLT apoptosis and inducing epigenetic changes that promote ICI therapy resistance. ICI can also affect tissue resident memory T cell population, impact tolerance in the post-transplant period, and induce acute inflammation risking graft survival post-transplant. Their interaction with immunosuppression may be key in reducing tumor burden and may thus, require multimodal therapy to treat these tumors. This review summarizes ICI use in the liver transplantation period, their impact on tolerance and resistance, and new potential therapies for combination or sequential treatments for liver tumors.
Collapse
Affiliation(s)
- Vivian Ortiz
- Division of Gastroenterology, Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, Missouri.
| | | |
Collapse
|
11
|
Di Martino M, Nicolazzi M, Baroffio P, Polidoro MA, Colombo Mainini C, Pocorobba A, Bottini E, Donadon M. A critical analysis of surgical outcomes indicators in hepato-pancreato-biliary surgery: From crude mortality to composite outcomes. World J Surg 2024; 48:2174-2186. [PMID: 39129054 DOI: 10.1002/wjs.12277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Accepted: 06/24/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND Indicators of surgical outcomes are designed to objectively evaluate surgical performance, enabling comparisons among surgeons and institutions. In recent years, there has been a surge in complex indicators of perioperative short-term and long-term outcomes. The aim of this narrative review is to provide an overview and a critical analysis of surgical outcomes indicators, with a special emphasis on hepato-pancreato-biliary (HPB) surgery. METHODS A narrative review of outcome measures was conducted using a combined text and MeSH search strategy to identify relevant articles focused on perioperative outcomes, specifically within HPB surgery. RESULTS The literature search yielded 624 records, and 94 studies were included in the analysis. Included papers were classified depending on whether they assessed intraoperative or postoperative specific or composite outcomes, and whether they assessed purely clinical or combined clinical and socio-economic indicators. Specific indicators included in composite outcomes were categorized into three main domains: intraoperative metrics, postoperative outcomes, and oncological outcomes. While postoperative mortality, complications, hospital stay and readmission were the indicators most frequently included in composite outcomes, oncological outcomes were rarely considered. CONCLUSIONS The evolution of surgical outcomes has shifted from the simplistic assessment of crude mortality rates to complex composite outcomes. Whether the recent explosion of publications on these topics has a clinical impact in real life is questionable. Outcomes from the patient perspective, integrating social and financial indicators, are not yet integrated into most of these composite analytical tools but should not be underestimated.
Collapse
Affiliation(s)
- Marcello Di Martino
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Department of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Marco Nicolazzi
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Department of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Paolo Baroffio
- Department of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| | - Michela Anna Polidoro
- Hepatobiliary Immunopathology Laboratory, IRCCS Humanitas Research Hospital, Milan, Italy
| | | | - Amanda Pocorobba
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Eleonora Bottini
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Matteo Donadon
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
- Department of Surgery, University Maggiore Hospital della Carità, Novara, Italy
| |
Collapse
|
12
|
Masior Ł, Krasnodębski M, Smoter P, Morawski M, Kobryń K, Hołówko W, Figiel W, Krawczyk M, Wróblewski T, Grąt M. Rescue liver transplantation for post-hepatectomy liver failure- single center retrospective analysis. BMC Surg 2024; 24:224. [PMID: 39107752 PMCID: PMC11301979 DOI: 10.1186/s12893-024-02515-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 07/29/2024] [Indexed: 08/10/2024] Open
Abstract
INTRODUCTION Liver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF. METHODS Relevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed. RESULTS Between January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24-66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively. CONCLUSIONS In an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group.
Collapse
Affiliation(s)
- Łukasz Masior
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland.
| | - Maciej Krasnodębski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Piotr Smoter
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Marcin Morawski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Konrad Kobryń
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Wacław Hołówko
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Wojciech Figiel
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Marek Krawczyk
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Tadeusz Wróblewski
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Banacha Street 1A, Warsaw, 02-097, Poland
| |
Collapse
|
13
|
Patrono D, De Stefano N, Romagnoli R. Liver transplantation for tumor entities. Curr Opin Organ Transplant 2024; 29:255-265. [PMID: 38716718 DOI: 10.1097/mot.0000000000001149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/03/2024]
Abstract
PURPOSE OF REVIEW Tumor entities represent an increasing indication for liver transplantation (LT). This review addresses the most contentious indications of LT in transplant oncology. RECENT FINDINGS Patient selection based on tumor biology in LT for colorectal cancer liver metastases (CRLM) demonstrated promising long-term outcomes and preserved quality of life despite high recurrence rates. In selected cases, LT for intrahepatic cholangiocarcinoma (iCCA) is feasible, with acceptable survival even in high-burden cases responsive to chemotherapy. LT following a strict neoadjuvant protocol for perihilar cholangiocarcinoma (pCCA) resulted in long-term outcomes consistently surpassing benchmark values, and potentially outperforming liver resection. SUMMARY While preliminary results are promising, prospective trials are crucial to define applications in routine clinical practice. Molecular profiling and targeted therapies pave the way for personalized approaches, requiring evolving allocation systems for equitable LT access.
Collapse
Affiliation(s)
- Damiano Patrono
- General Surgery 2U - Liver Transplant Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino - University of Turin, Turin, Italy
| | | | | |
Collapse
|
14
|
Sugawara Y, Hibi T. Recent trends and new developments in liver transplantation. Biosci Trends 2024; 18:206-211. [PMID: 38945855 DOI: 10.5582/bst.2024.01176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/02/2024]
Abstract
Liver transplantation (LT) has been an established treatment for end-staged liver disease for acute, chronic, metabolic diseases and liver cancer. Advanced surgical techniques, refined indications and contraindications for LT, improvements of donor selection, prognostic scorings system and immunosuppressive regimens have contributed to the improved outcomes of liver transplantation. The etiologies of cirrhosis have been shifting from viral hepatitis to metabolic associated fatty liver disease. New indications include peripheral or mass forming bile duct cancer, metastases from bowel cancers or neuroendocrine tumors. Resection and partial liver segments 2-3 transplantation with delayed total hepatectomy has been performed to the limited cases, which was the explored technique of auxiliary partial orthotopic LT. Minimally invasive donor hepatectomy (laparoscopic or robotic) has been increasingly done. In this review are described the recent pressing topics in LT.
Collapse
Affiliation(s)
- Yasuhiko Sugawara
- Department of Transplantation/Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan
| | - Taizo Hibi
- Department of Transplantation/Pediatric Surgery, Postgraduate School of Life Science, Kumamoto University, Kumamoto, Japan
| |
Collapse
|
15
|
Howell TC, Rhodin KE, Shaw B, Bao J, Kanu E, Masoud S, Bartholomew AJ, Gao Q, Anwar IJ, Ladowski JM, Nussbaum DP, Blazer DG, Zani S, Allen PJ, Barbas AS, Lidsky ME. Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma. J Gastrointest Surg 2024; 28:738-745. [PMID: 38704208 DOI: 10.1016/j.gassur.2024.02.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 11/10/2023] [Accepted: 02/17/2024] [Indexed: 05/06/2024]
Abstract
BACKGROUND Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.
Collapse
Affiliation(s)
- Thomas Clark Howell
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Kristen E Rhodin
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Brian Shaw
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Jiayin Bao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Elishama Kanu
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabran Masoud
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Alex J Bartholomew
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Qimeng Gao
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Imran J Anwar
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Joseph M Ladowski
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Daniel P Nussbaum
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Dan G Blazer
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Sabino Zani
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Peter J Allen
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Andrew S Barbas
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States
| | - Michael E Lidsky
- Department of Surgery, Duke University Medical Center, Durham, North Carolina, United States.
| |
Collapse
|
16
|
Rompianesi G, Montalti R, Vrakas G, Zarrinpar A, Warren C, Loiaco G, Rubba F, Troisi RI. Benchmark Outcomes in Deceased Donor Kidney Transplantation: A Multicenter Analysis of 80 996 Transplants From 126 Centers. Transplant Direct 2024; 10:e1618. [PMID: 38606349 PMCID: PMC11005896 DOI: 10.1097/txd.0000000000001618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 02/05/2024] [Accepted: 02/08/2024] [Indexed: 04/13/2024] Open
Abstract
BACKGROUND We defined clinically relevant benchmark values in deceased donor kidney transplantation (KT), to assess the best achievable results in low-risk patient cohorts from experienced centers. METHODS We identified the "ideal" cases from the United Network for Organ Sharing Standard Transplant Analysis and Research files from centers performing ≥50 KT per year between 2010 and 2018. Cases have been selected based on the kidney donor profile index values (<35%), a cold ischemia time (CIT) ≤18 h, a HLA mismatch ≤4, and excluding blood group (ABO) incompatible, dual and combined transplants. The outcomes of the benchmark cohort have been compared with a group of patients excluded from the benchmark cohort because but not meeting 1 or more of the abovementioned criteria. RESULTS The 171 424 KT patients in the United Network for Organ Sharing Standard Transplant Analysis and Research files were screened and 8694 benchmark cases of a total of 80 996 KT (10.7%) from 126 centers meeting the selection criteria were identified. The benchmarks for 1-, 3-, and 5-y patient survival are ≥97%, ≥92.5%, and ≥86.7%, and ≥95.4%, ≥87.8%, and ≥79.6% for graft survival. Benchmark cutoff for hospital length of stay is ≤5 d, ≤23.6% for delayed graft function, and ≤7.5% and ≤9.1% for 6-mo and 1-y incidence of acute rejection. Overall 1-, 3-, and 5-y actuarial graft survivals were 96.6%, 91.1%, and 84.2% versus 93.5%, 85.4%, and 75.5% in the benchmark and comparison groups, respectively (P < 0.001). Overall 1-, 3-, and 5-y actuarial patient survivals were 98.1%, 94.8%, and 90.0% versus 96.6%, 91.1%, and 83.0% in the benchmark and comparison groups, respectively (P < 0.001). CONCLUSIONS For the first time, we quantified the best achievable postoperative results in an ideal scenario in deceased donor KT, aimed at improving the clinical practice guided by the comparison of center performances with the ideal outcomes defined.
Collapse
Affiliation(s)
- Gianluca Rompianesi
- Division of Hepato-Biliary-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital of Naples, Italy
| | - Roberto Montalti
- Division of Hepato-Biliary-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital of Naples, Italy
| | - Georgios Vrakas
- Department of Surgery, University of Florida, Gainesville, FL
| | - Ali Zarrinpar
- Department of Surgery, University of Florida, Gainesville, FL
| | - Curtis Warren
- Department of Surgery, University of Florida, Gainesville, FL
| | - Giuseppe Loiaco
- Division of Hepato-Biliary-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital of Naples, Italy
| | - Fabiana Rubba
- Public Health Department, Federico II University Hospital, Naples, Italy
| | - Roberto I. Troisi
- Division of Hepato-Biliary-Pancreatic, Minimally Invasive, Robotic Surgery and Kidney Transplantation, Department of Clinical Medicine and Surgery, Federico II University Hospital of Naples, Italy
| |
Collapse
|
17
|
Andraus W, Tustumi F, Santana AC, Pinheiro RSN, Waisberg DR, Lopes LD, Arantes RM, Santos VR, de Martino RB, D'Albuquerque LAC. Liver transplantation as an alternative for the treatment of perihilar cholangiocarcinoma: A critical review. Hepatobiliary Pancreat Dis Int 2024; 23:139-145. [PMID: 38310060 DOI: 10.1016/j.hbpd.2024.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 01/19/2024] [Indexed: 02/05/2024]
Abstract
BACKGROUND Perihilar cholangiocarcinoma (phCCC) is a dismal malignancy. There is no consensus regarding the best treatment for patients with unresectable phCCC. The present review aimed to gather the current pieces of evidence for liver transplantation and liver resection as a treatment for phCCC and to build better guidance for clinical practice. DATA SOURCES The search was conducted in PubMed, Embase, Cochrane, and LILACS. The related references were searched manually. Inclusion criteria were: reports in English or Portuguese literature that a) patients with confirmed diagnosis of phCCC; b) patients treated with a curative intent; c) patients with the outcomes of liver resection and liver transplantation. Case reports, reviews, letters, editorials, conference abstracts and papers with full-text unavailability were excluded from the analysis. RESULTS Most of the current literature is based on observational retrospective studies with low grades of evidence. Liver resection has better long-term outcomes than systemic chemotherapy or palliation therapy and liver transplantation is a good alternative for selected patients with unresectable phCCC. All candidates for resection or transplantation should be medically fit and free of intrahepatic or extrahepatic diseases. As a general rule, patients presenting with a tumor having a longitudinal size > 3 cm or extending below the cystic duct, lymph node disease, confirmed extrahepatic dissemination; intraoperatively diagnosed metastatic disease; a history of other malignancies within the last five years, and did not complete chemoradiation regimen and were medically unfit should not be considered for transplantation. Some of these criteria should be individually assessed. Liver transplantation or resection should only be considered in highly experienced hepatobiliary centers, and any decision-making must be based on a multidisciplinary evaluation. CONCLUSIONS phCCC is a complex condition with high morbidity. Surgical therapies, including hepatectomy and liver transplantation, are the best option for better long-term disease-free survival.
Collapse
Affiliation(s)
- Wellington Andraus
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil.
| | - Francisco Tustumi
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Alexandre Chagas Santana
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | | | - Daniel Reis Waisberg
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Liliana Ducatti Lopes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Rubens Macedo Arantes
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | - Vinicius Rocha Santos
- Department of Gastroenterology, Transplantation Unit, Universidade de São Paulo, São Paulo, Brazil
| | | | | |
Collapse
|
18
|
Liu W, Li G, Jin Y, Feng Y, Gao Z, Liu X, Zhou B, Zheng X, Pei X, Ying Y, Yu Q, Yan S, Hu C. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model. Open Med (Wars) 2024; 19:20240926. [PMID: 38584830 PMCID: PMC10998668 DOI: 10.1515/med-2024-0926] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 02/07/2024] [Accepted: 02/11/2024] [Indexed: 04/09/2024] Open
Abstract
Ex vivo liver resection combined with autologous liver transplantation offers the opportunity to treat otherwise unresectable hepatobiliary malignancies and has been applied in clinic. The implementation of enhanced recovery after surgery (ERAS) program improves the outcome of surgical procedures. This is a retrospective single-center study including 11 cases of patients with liver cancer that underwent autologous liver transplantation and received ERAS: cholangiocarcinoma of the hilar region (n = 5), intrahepatic cholangiocarcinoma (n = 3), gallbladder cancer (n = 1), liver metastasis from colorectal cancer (n = 1), and liver metastasis from gastrointestinal mesenchymal tumor (n = 1). There were no deaths within 30 days and major complications occurred in two patients, and four patients were readmitted upon the first month after the surgery. Median hospital stay was 20 days (range 13-44) and median open diet was Day 4 (range 2-9) after surgery and median early post-operative activity was Day 5 (range 2-9) after surgery. In conclusion, autologous liver transplantation is feasible in the treatment of otherwise unresectable hepatobiliary malignancies, and our study showed favorable results with autologous liver transplantation in ERAS modality. ERAS modality provides a good option for some patients whose tumors cannot be resected in situ and offers a chance for rapid recovery.
Collapse
Affiliation(s)
- Weifeng Liu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Guogang Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Yitian Jin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Yihui Feng
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Zhenzhen Gao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Xingyu Liu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Bo Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Xiang Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Xiangru Pei
- Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Yulian Ying
- Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Qian Yu
- Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Sheng Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, China
| | - Chenlu Hu
- Nursing Department, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
19
|
Lerut J. Liver transplantation and liver resection as alternative treatments for primary hepatobiliary and secondary liver tumors: Competitors or allies? Hepatobiliary Pancreat Dis Int 2024; 23:111-116. [PMID: 38195351 DOI: 10.1016/j.hbpd.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Accepted: 12/28/2023] [Indexed: 01/11/2024]
Affiliation(s)
- Jan Lerut
- Institute for Experimental and Clinical Research (IREC), Université catholique Louvain (UCL), Avenue Hippocrate 56, 1200 Woluwe Saint Pierre, Brussels, Belgium.
| |
Collapse
|
20
|
Dar FS, Abbas Z, Ahmed I, Atique M, Aujla UI, Azeemuddin M, Aziz Z, Bhatti ABH, Bangash TA, Butt AS, Butt OT, Dogar AW, Farooqi JI, Hanif F, Haider J, Haider S, Hassan SM, Jabbar AA, Khan AN, Khan MS, Khan MY, Latif A, Luck NH, Malik AK, Rashid K, Rashid S, Salih M, Saeed A, Salamat A, Tayyab GUN, Yusuf A, Zia HH, Naveed A. National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma. World J Gastroenterol 2024; 30:1018-1042. [PMID: 38577184 PMCID: PMC10989497 DOI: 10.3748/wjg.v30.i9.1018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/03/2024] [Accepted: 01/29/2024] [Indexed: 03/06/2024] Open
Abstract
A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26, 2023, at the Pakistan Kidney and Liver Institute & Research Centre (PKLI & RC) after initial consultations with the experts. The Pakistan Society for the Study of Liver Diseases (PSSLD) and PKLI & RC jointly organised this meeting. This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma (hCCA). The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients. This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation. The diagnostic and staging workup includes high-quality computed tomography, magnetic resonance imaging, and magnetic resonance cholangiopancreatography. Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis. However, histopathologic confirmation is not always required before resection. Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging. The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification. Selected patients with unresectable hCCA can be considered for liver transplantation. Adjuvant chemotherapy should be offered to patients with a high risk of recurrence. The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions. Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage. Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
Collapse
Affiliation(s)
- Faisal Saud Dar
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Zaigham Abbas
- Department of Hepatogastroenterology and Liver Transplantation, Dr. Ziauddin University Hospital, Karachi 75600, Sindh, Pakistan
| | - Irfan Ahmed
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
- University of Aberdeen, Aberdeen B24 3FX, United Kingdom
| | - Muhammad Atique
- Department of Pathology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Usman Iqbal Aujla
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | | | - Zeba Aziz
- Department of Oncology, Hameed Latif Hospital, Lahore 54000, Pakistan
| | - Abu Bakar Hafeez Bhatti
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Tariq Ali Bangash
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Amna Subhan Butt
- Department of Medicine, Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Osama Tariq Butt
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Abdul Wahab Dogar
- Department of Liver Transplant, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | - Javed Iqbal Farooqi
- Department of Medicine & Gastroenterology, Lifecare Hospital and Research Centre, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan
| | - Faisal Hanif
- Department of Hepatopancreatobiliary & Liver Transplant, Bahria International Hospital, Lahore 54000, Pakistan
| | - Jahanzaib Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Siraj Haider
- Department of Surgery, Hepatopancreatobiliary & Liver Transplant, Dow University of Health Sciences, Karachi 74800, Pakistan
| | - Syed Mujahid Hassan
- Department of Gastroenterology, Hepatology & Nutrition, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat 66020, Pakistan
| | | | - Aman Nawaz Khan
- Department of Radiology, Rehman Medical Institute, Peshawar 25000, Pakistan
| | - Muhammad Shoaib Khan
- Army Liver Transplant Unit, Pak Emirates Military Hospital, Rawalpindi 46000, Pakistan
| | - Muhammad Yasir Khan
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amer Latif
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Shaikh Zayed Hospital and Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Nasir Hassan Luck
- Department of Gastroenterology, Sindh Institute of Urology and Transplantation, Karachi 75500, Pakistan
| | - Ahmad Karim Malik
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Kamran Rashid
- Rashid Nursing Home and Cancer Clinic, Rashid Nursing Home and Cancer Clinic, Rawalpindi 46000, Pakistan
| | - Sohail Rashid
- Department of Hepatopancreatic Biliary Surgery & Liver Transplant, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Mohammad Salih
- Department of Gastroenterology and Hepatology, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Abdullah Saeed
- Department of Radiology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| | - Amjad Salamat
- Department of Gastroenterology and Hepatology, Quaid-e-Azam International Hospital, Rawalpindi 44000, Pakistan
| | - Ghias-un-Nabi Tayyab
- Department of Gastroenterology and Hepatology, Post Graduate Medical Institute, Lahore 54000, Pakistan
| | - Aasim Yusuf
- Department of Internal Medicine, Division of Gastroenterology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore 54000, Pakistan
| | - Haseeb Haider Zia
- Division of Hepatopancreatic Biliary Surgery & Liver Transplantation, Shifa International Hospital, Islamabad 44000, Pakistan
| | - Ammara Naveed
- Department of Gastroenterology & Hepatology, Pakistan Kidney and Liver Institute & Research Centre, Lahore 54000, Pakistan
| |
Collapse
|
21
|
Wu TC, Deng J, Chu FI, Sadeghi S, Finn R, Agopian VG, Lee P, Raldow AC. Single center experience using stereotactic body radiation therapy (SBRT) on orthotopic liver transplant protocol for unresectable cholangiocarcinoma. HPB (Oxford) 2024; 26:444-450. [PMID: 38142182 DOI: 10.1016/j.hpb.2023.12.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Revised: 08/21/2023] [Accepted: 12/08/2023] [Indexed: 12/25/2023]
Abstract
PURPOSE To evaluate tolerability, pathologic response, and disease outcomes utilizing pre-operative stereotactic body radiation therapy (SBRT) followed by consolidation chemotherapy (CHT) prior to orthotopic liver transplant (OLT) in unresectable cholangiocarcinoma (CCA). METHODS This was a retrospective chart review of patients treated on OLT protocol at a single tertiary center from 2012 to 2019. Patients received pre-operative SBRT (40-50 Gy in 5 fractions) followed by CHT until progression or OLT. Progression-free survival (PFS) and overall survival (OS) were compared via log-rank test and Cox proportional hazards regression. RESULTS 26 patients (84.6% hilar, 15.4% intrahepatic) were identified for analysis. Eight patients (30.8%) patients developed acute toxicity after SBRT, mostly grade 1 nausea. Nine (34.6%) patients underwent OLT of which 4 (44.4%) achieved a pathologic complete response (pCR). Five (55.6%) OLT patients, including 2 pCR, developed recurrence at a median time of 49.9 weeks after OLT. 3-year OS for the OLT and dropout cohort was 75% and 9%, respectively (p < 0.0001). OS in hilar tumors only was statistically different for those that achieved a pCR (p = 0.014). CONCLUSIONS Pre-operative SBRT is a well-tolerated and effective radiation technique as part of OLT protocol for unresectable CCA and conferred in a pCR rate of 44% within our cohort.
Collapse
Affiliation(s)
- Trudy C Wu
- Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite B265, Los Angeles, CA, 90095, USA.
| | - Jie Deng
- Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite B265, Los Angeles, CA, 90095, USA
| | - Fang-I Chu
- Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite B265, Los Angeles, CA, 90095, USA
| | - Saeed Sadeghi
- Department of Medical Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite 120B, Los Angeles, CA, 90095, USA
| | - Richard Finn
- Department of Medical Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite 120B, Los Angeles, CA, 90095, USA
| | - Vatche G Agopian
- Department of Liver Transplant Surgery, University of California, Los Angeles, 924 Westwood Blvd, Los Angeles, CA, 90024, USA
| | - Percy Lee
- Department of Radiation Oncology, City of Hope Orange County, Lennar Foundation Cancer Center, 1000 Fivepoint, Irvine, CA, 92618, USA
| | - Ann C Raldow
- Department of Radiation Oncology, University of California, Los Angeles, 200 Medical Plaza Driveway, Suite B265, Los Angeles, CA, 90095, USA
| |
Collapse
|
22
|
Wu TC, Smith CP, Li JS, Burton J, Jackson NJ, Tao R, Ludmir EB, Raldow AC. A systematic review and meta-analysis of pathologic complete response rates for patients with cholangiocarcinoma treated on liver transplant protocols. J Surg Oncol 2024; 129:574-583. [PMID: 37986552 DOI: 10.1002/jso.27511] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 09/26/2023] [Accepted: 11/04/2023] [Indexed: 11/22/2023]
Abstract
BACKGROUND AND OBJECTIVES: Many heterogenous orthotopic liver transplant (OLT) protocols exist for patients with unresectable cholangiocarcinoma. Little is known about the incidence, predictors for, and the significance of achieving a pathologic complete response (pCR). METHODS We performed a systematic review through September 2022 of the PubMed, Embase, and Web of Science databases. A random-effect meta-analysis was conducted to pool data across studies with reported pCR rates. Heterogeneity between treatment protocols was assessed via subgroup analysis. The pCR and 1-, 3-, and 5-year recurrence-free survival (RFS) and overall survival (OS) rates were extracted as outcomes of interest. RESULTS A total of 15 studies reported pCR rates and were grouped by use of the Mayo protocol (4/15), stereotactic body radiation therapy (2/15), and an Other category (9/15). The pooled pCR rate among all studies was 32%. Both radiation technique and duration of CHT showed no significant association with pCR (p = 0.05 and 0.13, respectively). Pooled 1-year RFS and OS after any neoadjuvant therapy and OLT was 80% (95% confidence interval [CI], 0.61-0.91), and 91% (95% CI, 0.87-0.94), respectively. There was no 1-year OS difference detected among the three groups. pCR was not associated with OS in the meta-regression. Pooled 3- and 5-year OS among all studies was 72% and 61%, respectively. CONCLUSIONS The pooled incidence of pCR was 32%. Differences in radiation technique did not appear to influence pCR rates and upon meta-regression, pCR was not a surrogate marker for survival.
Collapse
Affiliation(s)
- Trudy C Wu
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
| | - Clayton P Smith
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
| | - Joshua S Li
- Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, California, USA
| | - Jason Burton
- Louise M. Darling Biomedical Library, University of California Los Angeles, Los Angeles, California, USA
| | - Nicholas J Jackson
- Department of Medicine Statistics Core, University of California Los Angeles, Los Angeles, California, USA
| | - Randa Tao
- Department of Radiation Oncology, University of Utah, Salt Lake City, Utah, USA
| | - Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Ann C Raldow
- Department of Radiation Oncology, University of California Los Angeles, Los Angeles, California, USA
| |
Collapse
|
23
|
Elshami M, Ammori JB, Hardacre JM, Selfridge JE, Bajor D, Mohamed A, Chakrabarti S, Mahipal A, Winter JM, Ocuin LM. Surgical Resection Alone is Associated With Higher Long-Term Survival Than Multiagent Chemotherapy Alone for Patients With Localized Biliary Tract Cancers. J Surg Res 2024; 295:705-716. [PMID: 38141457 DOI: 10.1016/j.jss.2023.11.067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 07/17/2023] [Accepted: 11/12/2023] [Indexed: 12/25/2023]
Abstract
INTRODUCTION We compared long-term survival of patients with localized biliary tract cancers (BTCs) treated with either surgical resection or multiagent chemotherapy. METHODS Patients with localized BTC [gallbladder adenocarcinoma, extrahepatic cholangiocarcinoma, intrahepatic cholangiocarcinoma] were identified within the National Cancer Database (2010-2017). Piecewise-constant hazard modeling was used to estimate hazard ratios (HRs) at prespecified intervals: 0-30 d, 31-60 d, 61-90 d, and >90 d post-treatment. RESULTS A total of 5988 patients with localized BTC were identified: 2697 (45.0%) received multiagent chemotherapy and 3291 (55.0%) underwent surgical resection. Patients with gallbladder adenocarcinoma or extrahepatic cholangiocarcinoma who were treated with surgical resection had an associated decline in overall survival (OS) as compared to those treated with multiagent chemotherapy within 0-30 d of treatment initiation (gallbladder adenocarcinoma [adjusted HR = 3.94, 95% confidence interval [CI]: 1.77-8.80]; extrahepatic cholangiocarcinoma [adjusted HR = 4.88, 95% CI: 2.76-8.61]). However, there was an associated improvement in OS for patients treated with surgical resection after 90 d from treatment initiation (gallbladder adenocarcinoma [adjusted HR = 0.36, 95% CI: 0.28-0.46]; extrahepatic cholangiocarcinoma [adjusted HR = 0.27, 95% CI: 0.24-0.32]). Among patients with intrahepatic cholangiocarcinoma, those who underwent surgical resection had an associated improvement in OS at 31-60 d (adjusted HR = 0.63, 95% CI: 0.40-0.99) and a further associated increase in OS at 61-90 d (adjusted HR = 0.34, 95% CI: 0.21-0.54) and after 90 d (HR = 0.23, 95% CI: 0.21-0.27) of treatment initiation. CONCLUSIONS For patients with localized BTC, surgical resection alone is associated with improved long-term survival outcomes compared to multiagent chemotherapy alone.
Collapse
Affiliation(s)
- Mohamedraed Elshami
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - John B Ammori
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Jeffrey M Hardacre
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - J Eva Selfridge
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - David Bajor
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amr Mohamed
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Sakti Chakrabarti
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Amit Mahipal
- Division of Hematology and Oncology, Department of Medicine, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, Ohio
| | - Jordan M Winter
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | - Lee M Ocuin
- Division of Surgical Oncology, Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio.
| |
Collapse
|
24
|
Sonnenday CJ. Liver Transplantation for Hilar Cholangiocarcinoma. Surg Clin North Am 2024; 104:183-196. [PMID: 37953035 DOI: 10.1016/j.suc.2023.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2023]
Abstract
Hilar cholangiocarcinoma (hCCA) is an infiltrative disease that often presents with locally advanced and/or metastatic disease, with a minority of patients eligible for surgical resection. Select patients with unresectable hCCA, or patients with hCCA in the setting of primary sclerosing cholangitis, with tumors less than 3 cm and no evidence of extrahepatic disease, can be effectively treated with neoadjuvant chemoradiation followed by liver transplantation. Staging laparotomy documenting lack of occult metastatic disease, including a portal lymphadenectomy documenting no nodal metastases, is essential to achieve optimal outcomes. Overall 5 year survival among treated patients is approximately 60%.
Collapse
Affiliation(s)
- Christopher J Sonnenday
- Department of Surgery, University of Michigan Health, F6686 UH-South, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5296, USA.
| |
Collapse
|
25
|
Schneider MA, Kim J, Berlth F, Sugita Y, Grimminger PP, Sano T, Rosati R, Baiocchi GL, Bencivenga M, De Manzoni G, Nunobe S, Yang HK, Gutschow CA. Defining benchmarks for total and distal gastrectomy: global multicentre analysis. Br J Surg 2024; 111:znad379. [PMID: 38377359 PMCID: PMC10878554 DOI: 10.1093/bjs/znad379] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 10/04/2023] [Accepted: 10/04/2023] [Indexed: 02/22/2024]
Affiliation(s)
- Marcel André Schneider
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Jeesun Kim
- Department of Surgery, Seoul National University Cancer Hospital, Seoul, South Korea
| | - Felix Berlth
- Department of General, Visceral and Transplant Surgery, University Medical Centre Mainz, Mainz, Germany
| | - Yutaka Sugita
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Peter P Grimminger
- Department of General, Visceral and Transplant Surgery, University Medical Centre Mainz, Mainz, Germany
| | - Takeshi Sano
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | | | - Maria Bencivenga
- Department of Surgery, University Hospital of Verona, Verona, Italy
| | | | - Souya Nunobe
- Department of Gastroenterological Surgery, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University Cancer Hospital, Seoul, South Korea
| | | |
Collapse
|
26
|
Loosen SH, Leyh C, Neumann UP, Bock H, Weigel C, Luedde T, Roderburg C. Liver transplantation meets gastrointestinal cancer. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:62-72. [PMID: 38195110 DOI: 10.1055/a-2226-0123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Abstract
Liver transplantation (LT) has emerged as a standard of care for patients with end-stage liver disease, providing a life-saving intervention for patients with severely compromised liver function in both the acute and chronic setting. While LT has also become a routine procedure for early-stage hepatocellular carcinoma (HCC), offering a potential cure by treating both the tumor and the underlying liver disease, its relevance in the context of other malignancies such as cholangiocellular carcinoma (CCA), combined hepatocellular-cholangiocarcinoma (cHCC-CCA) or liver metastases is still the subject of intense debate and no definite recommendations have yet been established. This review summarizes the current therapeutic standards in the context of LT for gastrointestinal malignancies and provides a reflection and outlook on current scientific and clinical developments.
Collapse
Affiliation(s)
- Sven H Loosen
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Catherine Leyh
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Ulf Peter Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Aachen, Germany
- Department of Surgery and Transplantation, University Hospital Essen, Essen, Germany
| | - Hans Bock
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christian Weigel
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| | - Christoph Roderburg
- Department of Gastroenterology, Hepatology and Infectious Diseases, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Center for Integrated Oncology Aachen Bonn Cologne Düsseldorf (CIO ABCD), Düsseldorf, Germany
| |
Collapse
|
27
|
Hoyer DP, Neumann U. Liver Transplantation meets Cancer. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:35-36. [PMID: 38195105 DOI: 10.1055/a-2179-3157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2024]
Affiliation(s)
- Dieter P Hoyer
- General, Visceral and Transplantation Surgery, University Hospital Essen, Germany
| | - Ulf Neumann
- General, Visceral and Transplantation Surgery, University Hospital Essen, Germany
| |
Collapse
|
28
|
Wheless M, Agarwal R, Goff L, Lockney N, Padmanabhan C, Heumann T. Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma. Curr Treat Options Oncol 2024; 25:127-160. [PMID: 38177560 PMCID: PMC10824875 DOI: 10.1007/s11864-023-01153-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/19/2023] [Indexed: 01/06/2024]
Abstract
OPINION STATEMENT Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma. When resectable, definitive surgery followed by adjuvant chemotherapy (sometimes with selective radiation/chemoradiation) is current standard of care. Due to high recurrence rates, there is growing interest in the use of upfront/neoadjuvant therapy to improve surgical outcomes and to downstage patients who may not initially be resectable. Select patients with perihilar cholangiocarcinoma are being successfully treated with novel approaches such as liver transplant. In the advanced disease setting, combination gemcitabine and cisplatin remains the standard base for systemic therapy and was recently improved upon with the addition of immune checkpoint blockade to the chemotherapy doublet in the recently reported TOPAZ-1 and KEYNOTE-966 trials. Second-line all-comer treatments for these patients remain limited in both options and efficacy, so clinical trial participation should be strongly considered. With increased use of molecular testing, detection of actionable mutations and opportunities to receive indicated targeted therapies are on the rise and are the most significant driver of improved survival for patients with advanced stage disease. Though these targeted therapies are currently reserved for the second or later line, future trials are looking at moving these to earlier treatment settings and use in combination with chemotherapy and immunotherapy. In addition to cross-disciplinary management with surgical, medical, and radiation oncology, patient-centered care should also include collaboration with advanced endoscopists, palliative care specialists, and nutritionists to improve global patient outcomes.
Collapse
Affiliation(s)
- Margaret Wheless
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building Suite 798, Nashville, TN, 37232, USA
| | - Rajiv Agarwal
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building Suite 798, Nashville, TN, 37232, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Laura Goff
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building Suite 798, Nashville, TN, 37232, USA
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
| | - Natalie Lockney
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Chandrasekhar Padmanabhan
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
- Department of Surgery, Division of Surgical Oncology & Endocrine Surgery, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Thatcher Heumann
- Department of Medicine, Division of Hematology Oncology, Vanderbilt University Medical Center, 2220 Pierce Avenue, Preston Research Building Suite 798, Nashville, TN, 37232, USA.
- Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
| |
Collapse
|
29
|
Padmanaban V, Ruff SM, Pawlik TM. Multi-Disciplinary Care of Hilar Cholangiocarcinoma: Review of Guidelines and Recent Advancements. Cancers (Basel) 2023; 16:30. [PMID: 38201457 PMCID: PMC10778096 DOI: 10.3390/cancers16010030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/09/2023] [Accepted: 12/15/2023] [Indexed: 01/12/2024] Open
Abstract
Cholangiocarcinoma (CCA) is a rare malignancy of the intrahepatic and extrahepatic biliary ducts. CCA is primarily defined by its anatomic location: intrahepatic cholangiocarcinoma versus extrahepatic cholangiocarcinoma. Hilar cholangiocarcinoma (HC) is a subtype of extrahepatic cholangiocarcinoma that arises from the common hepatic bile duct and can extend to the right and/or left hepatic bile ducts. Upfront surgery with adjuvant capecitabine is the standard of care for patients who present with early disease and the only curative therapy. Unfortunately, most patients present with locally advanced or metastatic disease and must rely on systemic therapy as their primary treatment. However, even with current systemic therapy, survival is still poor. As such, research is focused on developing targeted therapies and multimodal strategies to improve overall prognosis. This review discusses the work-up and management of HC focused on the most up-to-date literature and ongoing clinical trials.
Collapse
Affiliation(s)
| | | | - Timothy M. Pawlik
- Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA; (V.P.)
| |
Collapse
|
30
|
Ruff SM, Cloyd JM, Pawlik TM. Annals of Surgical Oncology Practice Guidelines Series: Management of Primary Liver and Biliary Tract Cancers. Ann Surg Oncol 2023; 30:7935-7949. [PMID: 37691030 DOI: 10.1245/s10434-023-14255-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 08/22/2023] [Indexed: 09/12/2023]
Abstract
Primary cancers of the liver and biliary tract are rare and aggressive tumors that often present with locally advanced or metastatic disease. For patients with localized disease amenable to resection, surgery typically offers the best chance at curative-intent therapy. Unfortunately, the incidence of recurrence even after curative-intent surgery remains high. In turn, patients with hepatobiliary cancers commonly require multimodality therapy including a combination of resection, systemic therapy (i.e., targeted therapy, cytotoxic chemotherapy, immunotherapy), and/or loco-regional therapies. With advancements in the field, it is crucial for surgical oncologists to remain updated on the latest guidelines and recommendations for surgical management and optimal patient selection. Given the complex and evolving nature of treatment, this report highlights the latest practice guidelines for the surgical management of hepatobiliary cancers.
Collapse
Affiliation(s)
- Samantha M Ruff
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.
| |
Collapse
|
31
|
Hu CL, Han X, Gao ZZ, Zhou B, Tang JL, Pei XR, Lu JN, Xu Q, Shen XP, Yan S, Ding Y. Systematic sequential therapy for ex vivo liver resection and autotransplantation: A case report and review of literature. World J Gastrointest Surg 2023; 15:2663-2673. [PMID: 38111758 PMCID: PMC10725551 DOI: 10.4240/wjgs.v15.i11.2663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 09/30/2023] [Accepted: 10/25/2023] [Indexed: 11/26/2023] Open
Abstract
BACKGROUND Perihilar cholangiocarcinoma (pCCA) is a highly malignant tumor arising from the biliary tree. Radical surgery is the only treatment offering a chance of long-term survival. However, limited by the tumor's anatomic location and peri-vascular invasion, most patients lose the chance for curative treatment. Therefore, more methods to increase the resectability of tumors as well as to improve outcomes are needed. CASE SUMMARY A 68-year-old female patient had a hepatic hilar mass without obvious symptoms. Laboratory results showed hepatitis B positivity. Magnetic resonance imaging indicated that the mass (maximum diameter: 41 mm) invaded the left and right branches of the main portal vein, as well as the middle, left and right hepatic veins; enlarged lymph nodes were also detected in the hilum. The patient was diagnosed with pCCA, and the clinical stage was determined to be T4N1M0 (stage IIIC). Considering the tumor's anatomic location and vascular invasion, systematic conversion therapy followed by ex vivo liver resection and autotransplantation (ELRA) was determined as personalized treatment for this patient. Our original systemic sequential therapeutic strategy (lenvatinib and tislelizumab in combination with gemcitabine and cisplatin) was successfully adopted as conversion therapy because she achieved partial response after three cycles of treatment, without severe toxicity. ELRA, anastomotic reconstruction of the middle hepatic vein, right hepatic vein, root of portal vein, inferior vena cava and right hepatic artery, and lymph node dissection were performed at one month after systemic therapy. Pathological and immunohistochemical examination confirmed the diagnosis of pCCA with lymph node metastasis. Although the middle hepatic vein was partially obstructed four months later, hepatic vein stent implantation successfully addressed this problem. The patient has survived for 22 mo after the diagnosis, with no evidence of recurrence or metastasis. CONCLUSION An effective therapeutic strategy for conversion therapy greatly increases the feasibility and efficiency of ELRA.
Collapse
Affiliation(s)
- Chen-Lu Hu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xin Han
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Zhen-Zhen Gao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Bo Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jin-Long Tang
- Department of Pathology, Zhejiang University School of Medicine, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xiang-Ru Pei
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Jie-Nan Lu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Qin Xu
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Xiao-Ping Shen
- Department of Nursing, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Sheng Yan
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| | - Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
| |
Collapse
|
32
|
Sousa Da Silva RX, Breuer E, Shankar S, Kawakatsu S, Hołówko W, Santos Coelho J, Jeddou H, Sugiura T, Ghallab M, Da Silva D, Watanabe G, Botea F, Sakai N, Addeo P, Tzedakis S, Bartsch F, Balcer K, Lim C, Werey F, Lopez-Lopez V, Peralta Montero L, Sanchez Claria R, Leiting J, Vachharajani N, Hopping E, Torres OJM, Hirano S, Andel D, Hagendoorn J, Psica A, Ravaioli M, Ahn KS, Reese T, Montes LA, Gunasekaran G, Alcázar C, Lim JH, Haroon M, Lu Q, Castaldi A, Orimo T, Moeckli B, Abadía T, Ruffolo L, Dib Hasan J, Ratti F, Kauffmann EF, de Wilde RF, Polak WG, Boggi U, Aldrighetti L, McCormack L, Hernandez-Alejandro R, Serrablo A, Toso C, Taketomi A, Gugenheim J, Dong J, Hanif F, Park JS, Ramia JM, Schwartz M, Ramisch D, De Oliveira ML, Oldhafer KJ, Kang KJ, Cescon M, Lodge P, Rinkes IHMB, Noji T, Thomson JE, Goh SK, Chapman WC, Cleary SP, Pekolj J, Regimbeau JM, Scatton O, Truant S, Lang H, Fuks D, Bachellier P, Ohtsuka M, Popescu I, Hasegawa K, Lesurtel M, Adam R, Cherqui D, Uesaka K, Boudjema K, Pinto-Marques H, Grąt M, Petrowsky H, Ebata T, Prachalias A, Robles-Campos R, Clavien PA. Novel Benchmark Values for Open Major Anatomic Liver Resection in Non-cirrhotic Patients: A Multicentric Study of 44 International Expert Centers. Ann Surg 2023; 278:748-755. [PMID: 37465950 DOI: 10.1097/sla.0000000000006012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/20/2023]
Abstract
OBJECTIVE This study aims at establishing benchmark values for best achievable outcomes following open major anatomic hepatectomy for liver tumors of all dignities. BACKGROUND Outcomes after open major hepatectomies vary widely lacking reference values for comparisons among centers, indications, types of resections, and minimally invasive procedures. METHODS A standard benchmark methodology was used covering consecutive patients, who underwent open major anatomic hepatectomy from 44 high-volume liver centers from 5 continents over a 5-year period (2016-2020). Benchmark cases were low-risk non-cirrhotic patients without significant comorbidities treated in high-volume centers (≥30 major liver resections/year). Benchmark values were set at the 75th percentile of median values of all centers. Minimum follow-up period was 1 year in each patient. RESULTS Of 8044 patients, 2908 (36%) qualified as benchmark (low-risk) cases. Benchmark cutoffs for all indications include R0 resection ≥78%; liver failure (grade B/C) ≤10%; bile leak (grade B/C) ≤18%; complications ≥grade 3 and CCI ® ≤46% and ≤9 at 3 months, respectively. Benchmark values differed significantly between malignant and benign conditions so that reference values must be adjusted accordingly. Extended right hepatectomy (H1, 4-8 or H4-8) disclosed a higher cutoff for liver failure, while extended left (H1-5,8 or H2-5,8) were associated with higher cutoffs for bile leaks, but had superior oncologic outcomes, when compared to formal left hepatectomy (H1-4 or H2-4). The minimal follow-up for a conclusive outcome evaluation following open anatomic major resection must be 3 months. CONCLUSION These new benchmark cutoffs for open major hepatectomy provide a powerful tool to convincingly evaluate other approaches including parenchymal-sparing procedures, laparoscopic/robotic approaches, and alternative treatments, such as ablation therapy, irradiation, or novel chemotherapy regimens.
Collapse
Affiliation(s)
- Richard X Sousa Da Silva
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Eva Breuer
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Sadhana Shankar
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | - Shoji Kawakatsu
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Wacław Hołówko
- Department of General, Transplant and Liver Surgery, Medical University Warsaw, Warsaw, Poland
| | - João Santos Coelho
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Heithem Jeddou
- Department of Hepatobiliary and Digestive Surgery, Rennes University Hospital, Rennes, France
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Mohammed Ghallab
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Doris Da Silva
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - Genki Watanabe
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Florin Botea
- Department of Surgery and Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Nozomu Sakai
- Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Pietro Addeo
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospital, Strasbourg University, Strasbourg, France
| | - Stylianos Tzedakis
- Department of Hepatobiliary, Digestive and Endocrine Surgery, Cochin Hospital, Paris Cité University, Paris, France
| | - Fabian Bartsch
- Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany
| | - Kaja Balcer
- Department of Digestive Surgery and Transplantation, CHU Lille, University Lille, Lille, France
| | - Chetana Lim
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière, Sorbonne Université, Centre de Recherche de Saint-Antoine, Paris, France
| | - Fabien Werey
- Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France
| | - Victor Lopez-Lopez
- Clinic and University Virgen de la Arrixaca Hospital, IMIB, Murcia, Spain
| | - Luciana Peralta Montero
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Rodrigo Sanchez Claria
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | - Neeta Vachharajani
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO
| | - Eve Hopping
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Orlando J M Torres
- Department of Gastrointestinal Surgery, Hepatopancreatobiliary Unit, Presidente Dutra Hospital, São Luiz, Brazil
| | - Satoshi Hirano
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Daan Andel
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Jeroen Hagendoorn
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Alicja Psica
- Department of Transplantation and Hepatobiliary Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Matteo Ravaioli
- Hepato-biliary surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Keun Soon Ahn
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
| | - Tim Reese
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Leonardo A Montes
- General Surgery Department Liver, Pancreas and Intestinal Transplant Unit, Favaloro Foundation University Hospital, Buenos Aires, Argentina
| | - Ganesh Gunasekaran
- Department of Surgery, Division of HPB Service, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Cándido Alcázar
- Department of Surgery, HPB and Transplant Unit, General Universitary Hospital Alicante and Health and Biomedical Research Institute of Alicante, Alicante, Spain
| | - Jin Hong Lim
- Department of Surgery, Division of HBP Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Muhammad Haroon
- Department of HPB and Liver Transplant, Bahria International Hospital Orchard, Lahore, Pakistan
| | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Antonio Castaldi
- Department of Digestive Surgery and Liver Transplant Unit, University Côte d'Azur, CHU de Nice, Nice, France
| | - Tatsuya Orimo
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Beat Moeckli
- Division of Abdominal and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Teresa Abadía
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - Luis Ruffolo
- Department of HPB and Transplant Surgery, University of Rochester, Rochester, NY
| | - Josefina Dib Hasan
- Transplant Unit, Hospital Aleman de Buenos Aires, Buenos Aires, Argentina
| | - Francesca Ratti
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | | | - Roeland F de Wilde
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Wojciech G Polak
- Department of Surgery, Division of HPB and Transplant Surgery, Erasmus MC University Medical Center, Rotterdam, Netherlands
| | - Ugo Boggi
- Division of General and Transplant Surgery, University of Pisa, Pisa, Italy
| | - Luca Aldrighetti
- Division of Hepatobiliary Surgery, IRCCS San Raffaele Hospital, Vita-Salute University, Milan, Italy
| | - Lucas McCormack
- Transplant Unit, Hospital Aleman de Buenos Aires, Buenos Aires, Argentina
| | | | - Alejandro Serrablo
- HPB Surgical Division, Miguel Servet University Hospital, Zaragoza, Spain
| | - Christian Toso
- Division of Abdominal and Transplantation Surgery, University Hospitals of Geneva, Geneva, Switzerland
| | - Akinobu Taketomi
- Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Jean Gugenheim
- Department of Digestive Surgery and Liver Transplant Unit, University Côte d'Azur, CHU de Nice, Nice, France
| | - Jiahong Dong
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
| | - Faisal Hanif
- Department of HPB and Liver Transplant, Bahria International Hospital Orchard, Lahore, Pakistan
| | - Joon Seong Park
- Department of Surgery, Division of HBP Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - José M Ramia
- Department of Surgery, HPB and Transplant Unit, General Universitary Hospital Alicante and Health and Biomedical Research Institute of Alicante, Alicante, Spain
| | - Myron Schwartz
- Department of Surgery, Division of HPB Service, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Diego Ramisch
- General Surgery Department Liver, Pancreas and Intestinal Transplant Unit, Favaloro Foundation University Hospital, Buenos Aires, Argentina
| | - Michelle L De Oliveira
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Karl J Oldhafer
- Department of Surgery, Division of Hepatobiliary and Pancreatic Surgery, Asklepios Hospital Barmbek, Semmelweis University of Medicine, Asklepios Campus Hamburg, Hamburg, Germany
| | - Koo Jeong Kang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, School of Medicine, Keimyung University, Dongsan Hospital, Daegu, Republic of Korea
| | - Matteo Cescon
- Hepato-biliary surgery and Transplant Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Peter Lodge
- Department of Transplantation and Hepatobiliary Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Inne H M Borel Rinkes
- Department of Surgical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
| | - Takehiro Noji
- Department of Gastroenterological Surgery II, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - John-Edwin Thomson
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - Su Kah Goh
- Hepatobiliary Unit, Department of Surgery, Royal Adelaide Hospital, Adelaide & Hepatobiliary Unit, Department of Surgery, Flinders Medical Centre, Adelaide, Australia
| | - William C Chapman
- Department of Surgery, Section of Abdominal Organ Transplant, Washington University School of Medicine, St Louis, MO
| | - Sean P Cleary
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN
| | - Juan Pekolj
- Hepato-Pancreato-Biliary Surgery Section and Liver Transplant Unit, General Surgery Department, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Jean-Marc Regimbeau
- Department of Oncology and Digestive Surgery, CHU Amiens-Picardie, Amiens, France
| | - Olivier Scatton
- Department of Digestive, Hepato-Biliary and Pancreatic Surgery and Liver Transplantation, AP-HP Pitié-Salpêtrière, Sorbonne Université, Centre de Recherche de Saint-Antoine, Paris, France
| | - Stéphanie Truant
- Department of Digestive Surgery and Transplantation, CHU Lille, University Lille, Lille, France
| | - Hauke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital of Mainz, Mainz, Germany
| | - David Fuks
- Department of Hepatobiliary, Digestive and Endocrine Surgery, Cochin Hospital, Paris Cité University, Paris, France
| | - Philippe Bachellier
- Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospital, Strasbourg University, Strasbourg, France
| | - Masayuki Ohtsuka
- Department of General Surgery, Chiba University, Graduate School of Medicine, Chiba, Japan
| | - Irinel Popescu
- Department of Surgery and Transplantation, Fundeni Clinical Institute, Bucharest, Romania
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mickaël Lesurtel
- Department of HPB Surgery and Liver Transplantation, AP-HP Beaujon Hospital, University of Paris Cité, Clichy, France
| | - René Adam
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Daniel Cherqui
- Paul Brousse Hospital, AP-HP, University Paris-Saclay, Villejuif, France
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center Hospital, Shizuoka, Japan
| | - Karim Boudjema
- Department of Hepatobiliary and Digestive Surgery, Rennes University Hospital, Rennes, France
| | - Hugo Pinto-Marques
- Hepato-Biliary-Pancreatic and Transplantation Centre, Curry Cabral Hospital, Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
| | - Michał Grąt
- Department of General, Transplant and Liver Surgery, Medical University Warsaw, Warsaw, Poland
| | - Henrik Petrowsky
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Tomoki Ebata
- Division of Surgical Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Andreas Prachalias
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, London, UK
| | | | - Pierre-Alain Clavien
- Swiss HPB and Transplant Center Zurich, Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| |
Collapse
|
33
|
Li Z, Rammohan A, Gunasekaran V, Hong S, Chen ICY, Kim J, Hervera Marquez KA, Hsu SC, Kirimker EO, Akamatsu N, Shaked O, Finotti M, Yeow M, Genedy L, Dutkowski P, Nadalin S, Boehnert MU, Polak WG, Bonney GK, Mathur A, Samstein B, Emond JC, Testa G, Olthoff KM, Rosen CB, Heimbach JK, Taner T, Wong TC, Lo CM, Hasegawa K, Balci D, Cattral M, Sapisochin G, Selzner N, Bin Jeng L, Broering D, Joh JW, Chen CL, Suk KS, Rela M, Clavien PA. Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences. Ann Surg 2023; 278:798-806. [PMID: 37477016 DOI: 10.1097/sla.0000000000006038] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/22/2023]
Abstract
OBJECTIVE To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.
Collapse
Affiliation(s)
- Zhihao Li
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland
| | - Ashwin Rammohan
- The Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, TN, India
| | - Vasanthakumar Gunasekaran
- The Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, TN, India
| | - Suyoung Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Itsuko Chih-Yi Chen
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jongman Kim
- Department of Surgery, Samsung Medical Center, Seoul, South Korea
| | - Kris Ann Hervera Marquez
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Shih Chao Hsu
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | | | - Nobuhisa Akamatsu
- Artificial Organ and Transplantation Division and Hepato-Biliary-Pancreatic Surgery, University of Tokyo, Tokyo, Japan
| | - Oren Shaked
- Division of Transplantation, University of Pennsylvania, Philadelphia, PA
| | - Michele Finotti
- Division of Abdominal Transplantation, Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Marcus Yeow
- Division of Hepatobiliary, Pancreatic Surgery and Liver Transplantation, University Surgical Cluster, National University Health System, Singapore
| | - Lara Genedy
- Department of General Visceral and Transplant Surgery, Eberhard Karls University of Tübingen, Tübingen, Germany
| | - Philipp Dutkowski
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland
| | - Silvio Nadalin
- Department of General Visceral and Transplant Surgery, Eberhard Karls University of Tübingen, Tübingen, Germany
| | - Markus U Boehnert
- Department of Surgery, Division of HPB and Transplant Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Wojciech G Polak
- Department of Surgery, Division of HPB and Transplant Surgery, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Glenn K Bonney
- Division of Hepatobiliary, Pancreatic Surgery and Liver Transplantation, University Surgical Cluster, National University Health System, Singapore
| | - Abhishek Mathur
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, NY
| | - Benjamin Samstein
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, NY
| | - Jean C Emond
- Liver and Abdominal Transplant Surgery, Columbia University Irving Medical Center, New York, NY
| | - Giuliano Testa
- Division of Abdominal Transplantation, Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX
| | - Kim M Olthoff
- Division of Transplantation, University of Pennsylvania, Philadelphia, PA
| | - Charles B Rosen
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN
| | - Julie K Heimbach
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN
| | - Timucin Taner
- Department of Surgery, Division of Transplantation Surgery, Mayo Clinic, Rochester, MN
| | - Tiffany Cl Wong
- Department of Surgery, The University of Hong Kong, Hong Kong, People's Republic of China
| | - Chung-Mau Lo
- Department of Surgery, The University of Hong Kong, Hong Kong, People's Republic of China
| | - Kiyoshi Hasegawa
- Artificial Organ and Transplantation Division and Hepato-Biliary-Pancreatic Surgery, University of Tokyo, Tokyo, Japan
| | - Deniz Balci
- Department of Surgery, Ankara University School of Medicine, Ankara, Turkey
| | - Mark Cattral
- Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Gonzalo Sapisochin
- Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Nazia Selzner
- Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Long Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, Taichung, Taiwan
| | - Dieter Broering
- Organ Transplant Center of Excellence, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Jae-Won Joh
- Department of Surgery, Samsung Medical Center, Seoul, South Korea
| | - Chao-Long Chen
- Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Kyung-Suh Suk
- Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Mohamed Rela
- The Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Centre, Chennai, TN, India
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Switzerland
| |
Collapse
|
34
|
Chiche L, Yang HK, Abbassi F, Robles-Campos R, Stain SC, Ko CY, Neumayer LA, Pawlik TM, Barkun JS, Clavien PA. Quality and Outcome Assessment for Surgery. Ann Surg 2023; 278:647-654. [PMID: 37555327 DOI: 10.1097/sla.0000000000006077] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/10/2023]
Abstract
This forum summarizes the proceedings of the joint European Surgical Association (ESA)/American Surgical Association (ASA) symposium on Quality and Outcome Assessment for Surgery that took place in Bordeaux, France, as part of the celebrations of the 30th anniversary of the ESA. Three presentations focused on a) the main messages from the Outcome4Medicine Consensus Conference, which took place in Zurich, Switzerland, in June 2022, b) the patient perspective, and c) benchmarking were hold by ESA members and discussed by ASA members in a symposium attended by members of both associations.
Collapse
Affiliation(s)
| | - Han-Kwang Yang
- Seoul National University College of Medicine, Seoul, Republic of Korea
| | | | | | | | - Clifford Y Ko
- University of California at Los Angeles and the American College of Surgeons, Los Angeles, CA
| | - Leigh A Neumayer
- University of Florida, College of Medicine-Jacksonville, Jacksonville, FL
| | | | - Jeffrey S Barkun
- Department of Surgery, Faculty of Medicine, McGill University, Montreal, QC, Canada
| | | |
Collapse
|
35
|
Fuchs B, Schelling G, Elyes M, Studer G, Bode-Lesniewska B, Scaglioni MF, Giovanoli P, Heesen P, on behalf of the SwissSarcomaNetwork. Unlocking the Power of Benchmarking: Real-World-Time Data Analysis for Enhanced Sarcoma Patient Outcomes. Cancers (Basel) 2023; 15:4395. [PMID: 37686671 PMCID: PMC10486409 DOI: 10.3390/cancers15174395] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 08/27/2023] [Accepted: 08/29/2023] [Indexed: 09/10/2023] Open
Abstract
Benchmarking is crucial for healthcare providers to enhance quality and efficiency, notably for complex conditions like sarcomas. Multidisciplinary teams/sarcoma boards (MDT/SBs) are vital in sarcoma management, but differences in their processes can affect patient outcomes and treatment costs, despite adherence to international guidelines. To address this issue, this study aimed to compare two MDT/SBs and establish an interoperable digital platform, Sarconnector®, for real-time-world data assessment and automated analysis. The study included 983 patients, 46.0% of whom female, with a median age of 58 years, and 4.5% of patients presented with metastasis at diagnosis. Differences were observed in the number of first-time presentations, follow-up presentations, primary sarcomas, biopsies and chemotherapy indications between the two MDT/SB. The results highlight the importance of benchmarking and utilizing a harmonized data approach, such as the RWT approach provided by the Sarconnector®, to standardize and evaluate quality and cost metrics. By identifying areas of improvement and making data-driven decisions on the meta-level, healthcare providers can optimize resources and improve patient outcomes. In conclusion, benchmarking with the RWT harmonized data approach provided by the Sarconnector® can help healthcare providers improve the overall effectiveness of the healthcare system and achieve better outcomes for their patients in terms of both outcomes and costs.
Collapse
Affiliation(s)
- Bruno Fuchs
- Sarcoma Service, University Teaching Hospital LUKS, University of Lucerne, 6000 Lucerne, Switzerland
- University Hospital USZ, University of Zurich, 8000 Zurich, Switzerland
- Sarcoma Service, Kantonsspital Winterthur, 8400 Winterthur, Switzerland
| | - Georg Schelling
- Sarcoma Service, University Teaching Hospital LUKS, University of Lucerne, 6000 Lucerne, Switzerland
- Sarcoma Service, Kantonsspital Winterthur, 8400 Winterthur, Switzerland
| | - Maria Elyes
- Sarcoma Service, University Teaching Hospital LUKS, University of Lucerne, 6000 Lucerne, Switzerland
| | - Gabriela Studer
- Sarcoma Service, University Teaching Hospital LUKS, University of Lucerne, 6000 Lucerne, Switzerland
| | - Beata Bode-Lesniewska
- Patho Enge, SSN Reference Sarcoma Pathology, University of Zurich, 8000 Zurich, Switzerland
| | - Mario F. Scaglioni
- Sarcoma Service, University Teaching Hospital LUKS, University of Lucerne, 6000 Lucerne, Switzerland
| | - Pietro Giovanoli
- University Hospital USZ, University of Zurich, 8000 Zurich, Switzerland
| | - Philip Heesen
- University Hospital USZ, University of Zurich, 8000 Zurich, Switzerland
| | | |
Collapse
|
36
|
Abstract
Successful surgery combines quality (achievement of a positive outcome) with safety (avoidance of a negative outcome). Outcome assessment serves the purpose of quality improvement in health care by establishing performance indicators and allowing the identification of performance gaps. Novel surgical quality metric tools (benchmark cutoffs and textbook outcomes) provide procedure-specific ideal surgical outcomes in a subgroup of well-defined low-risk patients, with the aim of setting realistic and best achievable goals for surgeons and centers, as well as supporting unbiased comparison of surgical quality between centers and periods of time. Validated classification systems have been deployed to grade adverse events during the surgical journey: (1) the ClassIntra classification for the intraoperative period; (2) the Clavien-Dindo classification for the gravity of single adverse events; and the (3) Comprehensive Complication Index (CCI) for the sum of adverse events over a defined postoperative period. The failure to rescue rate refers to the death of a patient following one or more potentially treatable postoperative adverse event(s) and is a reliable proxy of the institutional safety culture and infrastructure. Complication assessment is undergoing digital transformation to decrease resource-intensity and provide surgeons with real-time pre- or intraoperative decision support. Standardized reporting of complications informs patients on their chances to realize favorable postoperative outcomes and assists surgical centers in the prioritization of quality improvement initiatives, multidisciplinary teamwork, surgical education, and ultimately, in the enhancement of clinical standards.
Collapse
Affiliation(s)
- Fabian Kalt
- Department of Surgery and Transplantation, University Hospital Zurich, University of Zurich, Switzerland
| | - Hemma Mayr
- Department of Surgery and Transplantation, University Hospital Zurich, University of Zurich, Switzerland
| | - Daniel Gero
- Department of Surgery and Transplantation, University Hospital Zurich, University of Zurich, Switzerland
| |
Collapse
|
37
|
Domenghino A, Walbert C, Birrer DL, Puhan MA, Clavien PA. Consensus recommendations on how to assess the quality of surgical interventions. Nat Med 2023; 29:811-822. [PMID: 37069361 DOI: 10.1038/s41591-023-02237-3] [Citation(s) in RCA: 50] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 01/26/2023] [Indexed: 04/19/2023]
Abstract
Postoperative complications represent a major public health burden worldwide. Without standardized, clinically relevant and universally applied endpoints, the evaluation of surgical interventions remains ill-defined and inconsistent, opening the door for biased interpretations and hampering patient-centered health care delivery. We conducted a Jury-based consensus conference incorporating the perspectives of different stakeholders, who based their recommendations on the work of nine panels of experts. The recommendations cover the selection of postoperative outcomes from the perspective of patients and other stakeholders, comparison and interpretation of outcomes, consideration of cultural and demographic factors, and strategies to deal with unwarranted outcomes. With the recommendations developed exclusively by the Jury, we provide a framework for surgical outcome assessment and quality improvement after medical interventions, that integrates the main stakeholders' perspectives.
Collapse
Affiliation(s)
- Anja Domenghino
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland
| | | | - Dominique Lisa Birrer
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Milo A Puhan
- Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich (UZH), Zurich, Switzerland.
| | - Pierre-Alain Clavien
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland.
| |
Collapse
|
38
|
Patrono D, Colli F, Colangelo M, De Stefano N, Apostu AL, Mazza E, Catalano S, Rizza G, Mirabella S, Romagnoli R. How Can Machine Perfusion Change the Paradigm of Liver Transplantation for Patients with Perihilar Cholangiocarcinoma? J Clin Med 2023; 12:jcm12052026. [PMID: 36902813 PMCID: PMC10004136 DOI: 10.3390/jcm12052026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 02/24/2023] [Accepted: 03/01/2023] [Indexed: 03/08/2023] Open
Abstract
Perihilar cholangiocarcinomas (pCCA) are rare yet aggressive tumors originating from the bile ducts. While surgery remains the mainstay of treatment, only a minority of patients are amenable to curative resection, and the prognosis of unresectable patients is dismal. The introduction of liver transplantation (LT) after neoadjuvant chemoradiation for unresectable pCCA in 1993 represented a major breakthrough, and it has been associated with 5-year survival rates consistently >50%. Despite these encouraging results, pCCA has remained a niche indication for LT, which is most likely due to the need for stringent candidate selection and the challenges in preoperative and surgical management. Machine perfusion (MP) has recently been reintroduced as an alternative to static cold storage to improve liver preservation from extended criteria donors. Aside from being associated with superior graft preservation, MP technology allows for the safe extension of preservation time and the testing of liver viability prior to implantation, which are characteristics that may be especially useful in the setting of LT for pCCA. This review summarizes current surgical strategies for pCCA treatment, with a focus on unmet needs that have contributed to the limited spread of LT for pCCA and how MP could be used in this setting, with a particular emphasis on the possibility of expanding the donor pool and improving transplant logistics.
Collapse
|
39
|
Wu Y, Li S, Yuan J, Zhang H, Wang M, Zhang Z, Qin R. Benchmarking: a novel measuring tool for outcome comparisons in surgery. Int J Surg 2023; 109:419-428. [PMID: 37093075 PMCID: PMC10389472 DOI: 10.1097/js9.0000000000000212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 01/05/2023] [Indexed: 04/25/2023]
Abstract
INTRODUCTION Benchmarking, a novel measuring tool for outcome comparisons, is a recent concept in surgery. The objectives of this review are to examine the concept, definition, and evolution of benchmarking and its application in surgery. METHODS The literature about benchmarking was reviewed through an ever-narrowing search strategy, commencing from the concept, definition, and evolution of benchmarking to the application of benchmarking and experiences of benchmarking in surgery. PubMed, Web of Science, Embase, and Science Direct databases were searched until 20 September 2022, in the English language according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. RESULTS In the first phase of the literature search, the development of benchmarking was identified. The definitions of benchmarking evolved from a surveying term to a novel quality-improvement tool to assess the best achievable results in surgery. In the second phase, a total of 23 studies were identified about benchmarking in surgery, including esophagectomy, hepatic surgery, pancreatic surgery, rectum resection, and bariatric surgery. All studies were multicenter analyses from national, international, or global expert centers. Most studies (87.0%) adopted the definition that benchmark was the 75th percentile of the median values of centers. Performance metrics to define benchmarks were clinically relevant intraoperative and postoperative outcome indicators. CONCLUSION Benchmarking in surgery is a novel quality-improvement tool to define and measure the best achievable results, establishing a meaningful reference to evaluate surgical performance.
Collapse
Affiliation(s)
- Yi Wu
- Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | | | | | | | | | | | | |
Collapse
|
40
|
Choi WJ, Ivanics T, Gravely A, Gallinger S, Sapisochin G, O'Kane GM. Optimizing Circulating Tumour DNA Use in the Perioperative Setting for Intrahepatic Cholangiocarcinoma: Diagnosis, Screening, Minimal Residual Disease Detection and Treatment Response Monitoring. Ann Surg Oncol 2023; 30:3849-3863. [PMID: 36808320 DOI: 10.1245/s10434-023-13126-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 01/09/2023] [Indexed: 02/23/2023]
Abstract
In this review, we present the current evidence and future perspectives on the use of circulating tumour DNA (ctDNA) in the diagnosis, management and understanding the prognosis of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing surgery. Liquid biopsies or ctDNA maybe utilized to: (1) determine the molecular profile of the tumour and therefore guide the selection of molecular targeted therapy in the neoadjuvant setting, (2) form a surveillance tool for the detection of minimal residual disease or cancer recurrence after surgery, and (3) diagnose and screen for early iCCA detection in high-risk populations. The potential for ctDNA can be tumour-informed or -uninformed depending on the goals of its use. Future studies will require ctDNA extraction technique validations, with standardizations of both the platforms and the timing of ctDNA collections.
Collapse
Affiliation(s)
- Woo Jin Choi
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.,Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Tommy Ivanics
- Department of Surgery, Henry Ford Hospital, Detroit, MI, USA.,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Annabel Gravely
- HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Steven Gallinger
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada.,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada
| | - Gonzalo Sapisochin
- HBP and Multi Organ Transplant Program, Division of General Surgery, Department of Surgery, University Health Network, University of Toronto, Toronto, Ontario, Canada. .,HPB Surgical Oncology, University Health Network, Toronto, Ontario, Canada.
| | - Grainne M O'Kane
- Department of Medical Oncology, Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
| |
Collapse
|
41
|
Mauro E, Ferrer-Fàbrega J, Sauri T, Soler A, Cobo A, Burrel M, Iserte G, Forner A. New Challenges in the Management of Cholangiocarcinoma: The Role of Liver Transplantation, Locoregional Therapies, and Systemic Therapy. Cancers (Basel) 2023; 15:1244. [PMID: 36831586 PMCID: PMC9953927 DOI: 10.3390/cancers15041244] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 02/03/2023] [Accepted: 02/11/2023] [Indexed: 02/18/2023] Open
Abstract
Cholangiocarcinoma (CCA) is a neoplasm with high mortality that represents 15% of all primary liver tumors. Its worldwide incidence is on the rise, and despite important advances in the knowledge of molecular mechanisms, diagnosis, and treatment, overall survival has not substantially improved in the last decade. Surgical resection remains the cornerstone therapy for CCA. Unfortunately, complete resection is only possible in less than 15-35% of cases, with a risk of recurrence greater than 60%. Liver transplantation (LT) has been postulated as an effective therapeutic strategy in those intrahepatic CCA (iCCA) smaller than 3 cm. However, the low rate of early diagnosis in non-resectable patients justifies the low applicability in clinical practice. The evidence regarding LT in locally advanced iCCA is scarce and based on small, retrospective, and, in most cases, single-center case series. In this setting, the response to neoadjuvant chemotherapy could be useful in identifying a subgroup of patients with biologically less aggressive tumors in whom LT may be successful. The results of LT in pCCA are promising, however, we need a very careful selection of patients and adequate experience in the transplant center. Locoregional therapies may be relevant in unresectable, liver-only CCA. In iCCA smaller than 2 cm, particularly those arising in patients with advanced chronic liver disease in whom resection or LT may not be feasible, thermal ablation may become a reliable alternative. The greatest advances in the management of CCA occur in systemic treatment. Immunotherapy associated with chemotherapy has emerged as the gold standard in the first-line treatment. Likewise, the most encouraging results have been obtained with targeted therapies, where the use of personalized treatments has shown high rates of objective and durable tumor response, with clear signs of survival benefit. In conclusion, the future of CCA treatment seems to be marked by the development of new treatment strategies but high-quality, prospective studies that shed light on their use and applicability are mandatory.
Collapse
Affiliation(s)
- Ezequiel Mauro
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
| | - Joana Ferrer-Fàbrega
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Hepatobiliopancreatic Surgery and Liver and Pancreatic Transplantation Unit, Department of Surgery, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
| | - Tamara Sauri
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Medical Oncology Department, ICMHO, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alexandre Soler
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Radiology Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Amparo Cobo
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Nuclear Medicine Department, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Department of Interventional Radiology, CDI, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Gemma Iserte
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| | - Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC) Group, IDIBAPS, 08036 Barcelona, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Av. Monforte de Lemos, 3-5. Pabellón 11, Planta 0, 28029 Madrid, Spain
- Faculty of Medicine, University of Barcelona, C/ de Casanova, 143, 08036 Barcelona, Spain
- Liver Unit, Liver Oncology Unit, ICMDM, Hospital Clinic Barcelona, 08036 Barcelona, Spain
| |
Collapse
|
42
|
Lebertransplantation bei perihilärem Cholangiokarzinom. Zentralbl Chir 2023. [DOI: 10.1055/a-1989-4722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
|
43
|
Wang X, Liu ZP, Dai HS, Wang JJ, Chen ZY. Comment On: Liver Transplantation as a New Standard of Care in Patients with Perihilar Cholangiocarcinoma? Results from an International Benchmark Study. ANNALS OF SURGERY OPEN 2022; 3:e216. [PMID: 37600294 PMCID: PMC10406068 DOI: 10.1097/as9.0000000000000216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/02/2022] [Indexed: 03/05/2023] Open
Affiliation(s)
- Xiang Wang
- From the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, China
| | - Zhi-Peng Liu
- From the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, China
| | - Hai-Su Dai
- From the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, China
| | - Jing-Jing Wang
- From the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, China
| | - Zhi-Yu Chen
- From the Department of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Amy Medical University), Chongqing, China
| |
Collapse
|
44
|
Schlick K, Neumayer B, Neureiter D. What is the management of resected cholangiocarcinoma in terms of intra- and postoperative status of tumor margins and lymph nodes? A current view. Expert Rev Gastroenterol Hepatol 2022; 16:1019-1022. [PMID: 36472068 DOI: 10.1080/17474124.2022.2155633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Konstantin Schlick
- Oncologic Center, Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology, Infectiology and Rheumatology, Paracelsus Medical University, Salzburg, Austria.,Cancer Cluster Salzburg, Cancer Cluster
| | - Bettina Neumayer
- Cancer Cluster Salzburg, Cancer Cluster.,Institute of Pathology, University Clinics Salzburg, Paracelsus Medical University, Salzburg, Austria
| | - Daniel Neureiter
- Cancer Cluster Salzburg, Cancer Cluster.,Institute of Pathology, University Clinics Salzburg, Paracelsus Medical University, Salzburg, Austria
| |
Collapse
|