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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.
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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
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Pantea R, Bednarsch J, Schmitz S, Meister P, Heise D, Ulmer F, Neumann UP, Lang SA. The assessment of impaired liver function and prognosis in hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol 2024; 18:779-794. [PMID: 39688572 DOI: 10.1080/17474124.2024.2442573] [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: 10/16/2024] [Revised: 12/05/2024] [Accepted: 12/11/2024] [Indexed: 12/18/2024]
Abstract
INTRODUCTION The impairment of liver function strongly limits the therapeutic options for hepatocellular carcinoma (HCC), and the assessment of liver function is key to finding the appropriate therapy for patients suffering from this disease. Furthermore, preexisting liver dysfunction has a negative impact on the prognosis of patients in addition to the malignant potential of HCC. Hence, defining the optimal treatment of patients with HCC requires a comprehensive examination with liver function being a crucial part of it. AREAS COVERED This review will provide an overview of the currently existing methods for evaluating the liver function in patients with HCC. Assessment of liver function includes scoring systems but also functional and technical methods. In addition, the role of these tests in different treatment facilities such as liver resection, transplantation, interventional and systemic therapy is summarized. EXPERT OPINION A comprehensive pretherapeutic assessment of the liver function includes laboratory-based scoring systems, as well as imaging- and non-imaging-based functional tests. Combining diverse parameters can help to improve the safety and efficacy of HCC therapy particularly in patients with compromised liver function. Future research should focus on optimizing pretherapeutic assessment recommendations for each therapy.
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Affiliation(s)
- Roxana Pantea
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Jan Bednarsch
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Sophia Schmitz
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Phil Meister
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Daniel Heise
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Florian Ulmer
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Ulf Peter Neumann
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
| | - Sven Arke Lang
- Department of General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany
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Silva JCFD, Diniz AL, Torres SM, Silva DA, Ribeiro HSDC, de Godoy AL, de Farias IC, Felismino TC, da Costa Junior WL, Coimbra FJF. Influence of biliary and vascular resection types on morbidity in hepatectomies with vascular involvement. J Surg Oncol 2024. [PMID: 39104086 DOI: 10.1002/jso.27718] [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: 04/08/2024] [Accepted: 05/13/2024] [Indexed: 08/07/2024]
Abstract
INTRODUCTION Hepatectomies associated with vascular resections pose a technical challenge for surgeons, involving multiple reconstruction techniques. Moreover, adding clinical and surgical risks in the postoperative setting of these complex procedures are mainly due to prolonged surgical periods and potential complications inherent to vascular manipulation. Leveraging the expertise of a Cancer Center, we propose an institutional assessment utilizing the case series from A. C. Camargo Cancer Center in hepatectomies associated with vascular resection, evaluating postoperative complications and outcomes while highlighting clinical, laboratory, pathological, and surgical factors that may influence results. OBJECTIVE To assess mortality and morbidity associated with hepatectomies involving vascular resection. MATERIALS AND METHODS From a prospective database, a study was performed evaluating postoperative survival and morbidity using scoring systems such as Clavien-Dindo through a cohort analysis. RESULTS From a total of 1021 liver resections for a period of 10 years, 31 cases were evaluated from a unique cancer center in Brazil! Factors such as the performance of major hepatectomies, the need for blood transfusion, and the administration of neoadjuvant or adjuvant systemic therapy did not appear to influence the outcome of morbidity or mortality. However, the resection of the associated bile duct and the type of vascular resection seemed to influence morbidity outcomes with statistical significance (p = 0.006+ …). CONCLUSION Hepatectomies associated with vascular resections are safe in selected cases and when performed in referral centers. Factors such as associated bile duct resection and type of vascular resection should be considered for procedure indication.
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Affiliation(s)
| | - Alessandro L Diniz
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Silvio M Torres
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Dante A Silva
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - Héber S D C Ribeiro
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
| | - André Luiz de Godoy
- Department of Abdominal Surgery, A. C. Camargo Cancer Center, São Paulo, Brazil
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Pham AT, Truong CM, Trinh PH. Overcome intraoperative difficulties of ALPPS procedure: a single-center outcomes and technical experience. Ann Med Surg (Lond) 2024; 86:3833-3840. [PMID: 38989190 PMCID: PMC11230825 DOI: 10.1097/ms9.0000000000002161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 05/02/2024] [Indexed: 07/12/2024] Open
Abstract
Backgrounds/aims Recently, the ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) has become widely known to achieve hepatic resection by rapid future liver remnant hypertrophy, but it comes with intraoperative difficulties, followed by increased complications. This study aimed to report the outcomes of an oncology center in a low-income and middle-income country with ALPPS in patients with liver tumors and its technical variants, which were invented to overcome intraoperative difficulties of the ALPPS procedure. Patients and methods A retrospective analysis of patients undergoing ALPPS from September 2022 to December 2023 was performed. Results A total of 25 patients underwent the ALPPS procedure: 21 procedures for hepatocellular carcinoma (HCC), 3 combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and 1 for small cell neuroendocrine carcinoma (SNEC). The mean postoperative stay was 29.6 ± 9.3 days (range 16-58 days). After stage 1, we counted 8 complications, all of grade II; after stage 2, the number of complications was decreased to 3:2 were of grade I and 1 were of grade IIIB. 3 (12%) patients failed to proceed to ALPPS stage 2. After a median follow-up of 9 months (range 2-25), disease recurrence has been recorded in 3 patients (12%), while 1 patient (4%) died, affected by HCC. The entire group's 2-year overall survival (OS) and disease-free survival (DFS) were 83.3% and 82.5%, respectively. Conclusion The ALPPS procedure is an approach for large liver tumors with small future liver remnant with acceptable OS and DFS in a low-income and middle-income country.
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Affiliation(s)
| | - Cuong Manh Truong
- Department of Hepatobiliary and Pancreatic Surgery, Vietnam National Cancer Hospital, Hanoi, Vietnam
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O'Connell RM, Hoti E. Challenges and Opportunities for Precision Surgery for Colorectal Liver Metastases. Cancers (Basel) 2024; 16:2379. [PMID: 39001441 PMCID: PMC11240734 DOI: 10.3390/cancers16132379] [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: 05/28/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 07/16/2024] Open
Abstract
The incidence of colorectal cancer and colorectal liver metastases (CRLM) is increasing globally due to an interaction of environmental and genetic factors. A minority of patients with CRLM have surgically resectable disease, but for those who have resection as part of multimodal therapy for their disease, long-term survival has been shown. Precision surgery-the idea of careful patient selection and targeting of surgical intervention, such that treatments shown to be proven to benefit on a population level are the optimal treatment for each individual patient-is the new paradigm of care. Key to this is the understanding of tumour molecular biology and clinically relevant mutations, such as KRAS, BRAF, and microsatellite instability (MSI), which can predict poorer overall outcomes and a poorer response to systemic therapy. The emergence of immunotherapy and hepatic artery infusion (HAI) pumps show potential to convert previously unresectable disease to resectable disease, in addition to established systemic and locoregional therapies, but the surgeon must be wary of poor-quality livers and the spectre of post-hepatectomy liver failure (PHLF). Volume modulation, a cornerstone of hepatic surgery for a generation, has been given a shot in the arm with the advent of liver venous depletion (LVD) ensuring significantly more hypertrophy of the future liver remnant (FLR). The optimal timing of liver resection for those patients with synchronous disease is yet to be truly established, but evidence would suggest that those patients requiring complex colorectal surgery and major liver resection are best served with a staged approach. In the operating room, parenchyma-preserving minimally invasive surgery (MIS) can dramatically reduce the surgical insult to the patient and lead to better perioperative outcomes, with quicker return to function.
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Affiliation(s)
- Robert Michael O'Connell
- Department of Hepatopancreaticobiliary and Transplantation Surgery, Saint Vincent's University Hospital, D04 T6F4 Dublin, Ireland
| | - Emir Hoti
- Department of Hepatopancreaticobiliary and Transplantation Surgery, Saint Vincent's University Hospital, D04 T6F4 Dublin, Ireland
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Costa AC, Mazzotta A, Santa-Cruz F, Coelho FF, Tribillon E, Gayet B, Herman P, Soubrane O. Short-term outcomes of laparoscopic extended hepatectomy versus major hepatectomy: a single-center experience. HPB (Oxford) 2024; 26:818-825. [PMID: 38485564 DOI: 10.1016/j.hpb.2024.02.017] [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: 07/15/2023] [Revised: 02/16/2024] [Accepted: 02/25/2024] [Indexed: 06/02/2024]
Abstract
INTRODUCTION Laparoscopic major hepatectomy (LMH) remains restricted to a few specialized centers and poses a challenge to surgeons performing laparoscopic resections. Laparoscopic extended resections are even more complex and rarely conducted. METHODS From a single-institution database, we compared the short-term outcomes of patients who underwent major and extended laparoscopic resections, stratifying the entire retrospective cohort into four groups: right hepatectomy, left hepatectomy, right extended hepatectomy, and left extended hepatectomy. Patient demographics, tumor characteristics, operative variables, and especially postoperative outcomes were evaluated. RESULTS 250 patients underwent major and extended laparoscopic liver resections, including 160 right, 31 right extended, 36 left, and 23 left extended laparoscopic hepatectomies. The most common indication for resection was colorectal liver metastases (64%). Laparoscopic extended hepatectomy (LEH) showed significantly longer operative time, more blood loss, need for Pringle maneuver, conversion to open surgery, higher rates of liver failure, postoperative ascites, and intra-abdominal hemorrhage, R1 margins and length of stay when compared with the LMH group. Mortality rates were similar between groups. Multivariate analysis revealed intraoperative blood transfusion (OR = 5.1[CI-95%: 1.15-6.79]; p = 0.02) as an independent predictor for major complications. CONCLUSIONS LEH showed to be feasible, however with higher blood loss and significantly associated to major complications.
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Affiliation(s)
- Adriano C Costa
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France; Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil.
| | - Alessandro Mazzotta
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Fernando Santa-Cruz
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Fabricio F Coelho
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Ecoline Tribillon
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Brice Gayet
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
| | - Paulo Herman
- Department of Gastroenterology, Hospital das Clinicas, University of São Paulo Medical School, São Paulo, SP, Brazil
| | - Olivier Soubrane
- Department of Digestive, Metabolic and Oncologic Surgery, Institut Mutualiste Montsouris, University René Descartes Paris 5, Paris, France
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Esmail A, Badheeb M, Alnahar B, Almiqlash B, Sakr Y, Khasawneh B, Al-Najjar E, Al-Rawi H, Abudayyeh A, Rayyan Y, Abdelrahim M. Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation. Cancers (Basel) 2024; 16:1946. [PMID: 38893067 PMCID: PMC11171350 DOI: 10.3390/cancers16111946] [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: 04/09/2024] [Revised: 05/15/2024] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53-79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT.
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Affiliation(s)
- Abdullah Esmail
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Mohamed Badheeb
- Department of Internal Medicine, Yale New Haven Health, Bridgeport Hospital, Bridgeport, CT 06605, USA
| | - Batool Alnahar
- College of Medicine, Almaarefa University, Riyadh 13713, Saudi Arabia
| | - Bushray Almiqlash
- Zuckerman College of Public Health, Arizona State University, Tempe, AZ 85287, USA
| | - Yara Sakr
- Department of GI Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Bayan Khasawneh
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Ebtesam Al-Najjar
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
| | - Hadeel Al-Rawi
- Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Ala Abudayyeh
- Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Yaser Rayyan
- Department of Gastroenterology & Hepatology, Faculty of Medicine, The University of Jordan, Amman 11942, Jordan
| | - Maen Abdelrahim
- Section of GI Oncology, Department of Medicine, Houston Methodist Cancer Center, Houston, TX 77030, USA
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Duque P, Perez-Peña JM, Alarcon-Perez L, Olmedilla L, Varela JA, Pascual C, Rodriguez-Huerta AM, Asencio JM, Lopez-Baena JÁ, Garutti I. The link between high factor VIII to protein C ratio values and poor liver function after major hepatectomy. Blood Coagul Fibrinolysis 2024; 35:82-93. [PMID: 38305104 DOI: 10.1097/mbc.0000000000001277] [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: 02/03/2024]
Abstract
Our goal was to assess the coagulation profile in the immediate postoperative time after major liver surgery and its association with the liver function. Our hypothesis is that a decreased synthesis of the coagulation factor levels reflects an impaired liver synthesis following hepatic resection and will be associated with poor outcomes. This is a prospective, observational study recruiting consecutive patients scheduled for major liver resection in a tertiary hospital. Coagulation profile was assessed by conventional assays, viscoelastic assays and coagulation factor levels preoperatively and, on postoperative days 1, 2 and 6. Factor VIII to protein C (FVIII/PC) ratio has been used as a surrogate marker of hemostatic imbalance. Liver function was measured with conventional and indocyanine green (ICG) clearance tests, which were obtained preoperatively and on postoperative days 1 and 2. Sixty patients were recruited and 51 were included in the study. There is a clear increase in FVIII/PC ratio after surgery, which was significantly associated with low liver function, being more pronounced beyond postoperative day 2 and in patients with poorer liver function ( P < 0.001). High FVIII/PC ratio values were significantly associated with higher postoperative morbidity, prolonged ICU and hospital stay and less survival ( P < 0.05). High FVIII/PC ratio on postoperative day 2 was found to be predictor of posthepatectomy liver failure (PHLF; area under the ROC curve = 0.8129). Early postoperative high FVIII/PC ratio values are associated with low liver function, PHLF and poorer outcomes in patients undergoing major hepatic resection.
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Affiliation(s)
- Patricia Duque
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
| | | | | | - Luis Olmedilla
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
| | | | | | | | - José Manuel Asencio
- General Surgery Department, Gregorio Marañon Hospital
- Gregorio Marañon Health Research Institute
- Medical Faculty, Complutense University, Madrid, Spain
| | - Jose Ángel Lopez-Baena
- General Surgery Department, Gregorio Marañon Hospital
- Gregorio Marañon Health Research Institute
| | - Ignacio Garutti
- Anesthesiology Department
- Gregorio Marañon Health Research Institute
- Medical Faculty, Complutense University, Madrid, Spain
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Chandra P, Sacks GD. Contemporary Surgical Management of Colorectal Liver Metastases. Cancers (Basel) 2024; 16:941. [PMID: 38473303 DOI: 10.3390/cancers16050941] [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: 11/27/2023] [Revised: 02/13/2024] [Accepted: 02/19/2024] [Indexed: 03/14/2024] Open
Abstract
Colorectal cancer is the third most common cancer in the United States and the second most common cause of cancer-related death. Approximately 20-30% of patients will develop hepatic metastasis in the form of synchronous or metachronous disease. The treatment of colorectal liver metastasis (CRLM) has evolved into a multidisciplinary approach, with chemotherapy and a variety of locoregional treatments, such as ablation and portal vein embolization, playing a crucial role. However, resection remains a core tenet of management, serving as the gold standard for a curative-intent therapy. As such, the input of a dedicated hepatobiliary surgeon is paramount for appropriate patient selection and choice of surgical approach, as significant advances in the field have made management decisions extremely nuanced and complex. We herein aim to review the contemporary surgical management of colorectal liver metastasis with respect to both perioperative and operative considerations.
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Affiliation(s)
- Pratik Chandra
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
| | - Greg D Sacks
- Department of Surgery, NYU Grossman School of Medicine, New York, NY 10016, USA
- VA New York Harbor Healthcare System, New York, NY 10010, USA
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Khosla D, Misra S, Chu PL, Guan P, Nada R, Gupta R, Kaewnarin K, Ko TK, Heng HL, Srinivasalu VK, Kapoor R, Singh D, Klanrit P, Sampattavanich S, Tan J, Kongpetch S, Jusakul A, Teh BT, Chan JY, Hong JH. Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches. Cancers (Basel) 2024; 16:801. [PMID: 38398194 PMCID: PMC10887007 DOI: 10.3390/cancers16040801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Revised: 02/05/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.
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Affiliation(s)
- Divya Khosla
- Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Shagun Misra
- Department of Radiotherapy and Oncology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India
| | - Pek Lim Chu
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
| | - Peiyong Guan
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
| | - Ritambhra Nada
- Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Rajesh Gupta
- Department of GI Surgery, HPB, and Liver Transplantation, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Khwanta Kaewnarin
- SingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, Singapore
| | - Tun Kiat Ko
- Cancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, Singapore
| | - Hong Lee Heng
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
| | - Vijay Kumar Srinivasalu
- Department of Medical Oncology, Mazumdar Shaw Medical Center, NH Health City Campus, Bommasandra, Bangalore 560099, India
| | - Rakesh Kapoor
- Department of Radiotherapy and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India
| | - Deepika Singh
- SingHealth Duke-NUS Institute of Biodiversity Medicine, Singapore 168583, Singapore
| | - Poramate Klanrit
- Cholangiocarcinoma Screening and Care Program (CASCAP), Khon Kaen University, Khon Kaen 40002, Thailand
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Somponnat Sampattavanich
- Siriraj Center of Research Excellence for Systems Pharmacology, Department of Pharmacology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok 73170, Thailand
| | - Jing Tan
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
| | - Sarinya Kongpetch
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
- Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Apinya Jusakul
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen 40002, Thailand
- Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand
| | - Bin Tean Teh
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
- Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore 138672, Singapore
- Laboratory of Cancer Epigenome, Division of Medical Science, National Cancer Center Singapore, Singapore 168583, Singapore
- Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore 138673, Singapore
| | - Jason Yongsheng Chan
- Cancer Discovery Hub, National Cancer Center Singapore, Singapore 168583, Singapore
- Oncology Academic Clinical Program, Duke-NUS Medical School, Singapore 169857, Singapore
- Division of Medical Oncology, National Cancer Center, Singapore 168583, Singapore
| | - Jing Han Hong
- Cancer and Stem Cell Biology Programme, Duke-NUS Medical School, Singapore 169857, Singapore
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11
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Eguia E, Baker T, Baker M. Hepatocellular Carcinoma: Surgical Management and Evolving Therapies. Cancer Treat Res 2024; 192:185-206. [PMID: 39212922 DOI: 10.1007/978-3-031-61238-1_10] [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: 09/04/2024]
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the eighth most common cancer in women worldwide. It is also the second leading cause of cancer death worldwide, with 780,000 deaths in 2018. Seventy-two percent of HCC cases occur in Asia, 10% in Europe, 8% in Africa, 5% in North America, and 5% in Latin America (Singal et al. in J Hepatol 72(2):250-261, 2020 [1]).
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Affiliation(s)
- Emanuel Eguia
- Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Talia Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA
| | - Marshall Baker
- Huntsman Cancer Center, University of Utah Eccles School of Medicine, Salt Lake City, UT, USA.
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12
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Smet H, Martin D, Uldry E, Duran R, Girardet R, Schaefer N, Prior JO, Denys A, Halkic N, Demartines N, Melloul E. Tc-99m mebrofenin hepatobiliary scintigraphy to assess future liver remnant function before major liver surgery. J Surg Oncol 2023; 128:1312-1319. [PMID: 37638473 DOI: 10.1002/jso.27426] [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: 06/07/2023] [Accepted: 08/12/2023] [Indexed: 08/29/2023]
Abstract
BACKGROUND AND OBJECTIVES Assessment of liver function is paramount before hepatectomy. This study aimed to assess future liver remnant function (FLR-F) using hepatobiliary scintigraphy (HBS) and to compare it to FLR volume (FLR-V) in the prediction of posthepatectomy liver failure (PHLF). The impact of volume and function gains were also assessed in patients undergoing portal vein embolization (PVE) or liver venous deprivation (LVD). METHODS All consecutive patients undergoing major hepatectomy between 02/2018 and 09/2021 with preoperative HBS were included. FLR-V was expressed as percentage of total liver volume and analyzed using preoperative computed tomography. FLR-V and FLR-F gains after embolization were expressed in percentage. Receiver operating characteristic analysis was performed to compare both methods in predicting PHLF. RESULTS Thirty-six patients were included. PVE and LVD were performed in 4 (11%) and 28 patients (78%), respectively. Overall, PHLF occurred in eight patients (22%). FLR-F gain after embolization showed significant ability to predict PHLF (area under the curve [AUC] = 0.789), with cut-off value of 150% showing a sensitivity of 1.00, a specificity of 0.42, and a negative predictive value of 1.00. CONCLUSION Preoperative HBS shows a high sensitivity to predict PHLF when HBS is performed twice to measure the function gain after venous embolization.
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Affiliation(s)
- Héloïse Smet
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - David Martin
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emilie Uldry
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Rafaël Duran
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Raphael Girardet
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Niklaus Schaefer
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - John O Prior
- Department of Nuclear Medicine and Molecular Imaging, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Alban Denys
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nermin Halkic
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Nicolas Demartines
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
| | - Emmanuel Melloul
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne and University of Lausanne (UNIL), Lausanne, Switzerland
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13
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Lin K, Cao J, Chen H, Topatana W, Cai J, Zhang B, Hu J, Jin R. Research trends in cholangiocarcinoma treatments during the last 3 decades. Heliyon 2023; 9:e17100. [PMID: 37455974 PMCID: PMC10338968 DOI: 10.1016/j.heliyon.2023.e17100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 06/05/2023] [Accepted: 06/07/2023] [Indexed: 07/18/2023] Open
Abstract
Background Over the past 30 years, numerous studies have focused on the treatment of cholangiocarcinoma (CCA), and these treatments have greatly evolved. Objectives To better understand the research trends, we evaluated the most influential publications and attempted to identify their characteristics using bibliometric methods. Methods The most influential publications were identified from the Clarivate Analytics Web of Science Core Collection database. The general characteristics of included papers were identified, and the research trends were explored via the bibliometric method. Results The average total number of citations for of the listed publications were 312 (range from 165 to 1922). The highest number of papers were published during period II (2001-2010, n = 50), followed by period III (2011-2020, n = 28), and period I (1991-2000, n = 22). The United States and Germany have made remarkable achievements in this field. Institutionally, Mayo Clinic and Memorial Sloan-Kettering Cancer Center were the leading institutions, with Blumgart and Zhu from the United States being the most influential authors. Close collaboration was established between the leading countries, institutions, and authors. The Annals of Surgery contributed the most to the papers with the highest total number of citations. Surgery predominated during period I (n = 14, 63.6%), with a gradual decline occurring during periods II (n = 19, 41.3%, P = 0.085) and period III (n = 3, 9.4%, P = 0.002). Contrastingly, the number of publications related to systemic therapy has increased significantly since period II and peaked in period III. Conclusions Surgery remains the most important treatment for CCA. However systemic therapy has become a research and clinical application hotspot. These findings will contribute to the translation of treatments for CCA and provide researchers with relevant research directions.
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Affiliation(s)
- Kainan Lin
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Jiasheng Cao
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Haibo Chen
- Department of Gastrointestinal Surgery, The First People's Hospital of Wenling, Taizhou, 317500, Zhejiang Province, China
| | - Win Topatana
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Jingwei Cai
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Bin Zhang
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Jiahao Hu
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
| | - Renan Jin
- Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310058, Zhejiang Province, China
- Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, Zhejiang Province, China
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14
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Takayama S, Yokoyama K, Ishikawa K, Tomoda K, Suzuki H, Takayama S. Simultaneous robot-assisted colorectal surgery for sigmoid colon cancer and portal vein embolization from the inferior mesenteric vein for intrahepatic cholangiocarcinoma: A case report and literature review. Int J Surg Case Rep 2023; 106:108180. [PMID: 37058807 PMCID: PMC10123244 DOI: 10.1016/j.ijscr.2023.108180] [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: 01/24/2023] [Revised: 02/28/2023] [Accepted: 03/01/2023] [Indexed: 04/16/2023] Open
Abstract
INTRODUCTION AND IMPORTANCE The treatment of multiple cancers requires multidisciplinary expertise. In this case, we experienced a multiple cancers case, sigmoid colon cancer and intrahepatic cholangiocarcinoma that required preoperative portal vein embolization (PVE). PVE is often approached by trans-hepatic percutaneous approach or via ileocecal vein (ICV) or veins of the small intestine. In this case, the patient was scheduled to undergo robot-assist surgery for sigmoid colon cancer, and it was planned that the inferior mesenteric vein (IMV) would be cut. PVE from the IMV was performed with hope to reduce complications. CASE PRESENTATION This patient had intrahepatic cholangiocarcinoma and sigmoid colon cancer. A radical cure for intrahepatic cholangiocarcinoma was expected by left liver lobectomy. Because of concerns about postoperative liver failure, it was decided to perform PVE. PVE via IMV approach was performed simultaneously with robot-assisted surgery for sigmoid colon cancer. The patient was discharged without complications 12 days after surgery. CLINICAL DISCUSSION PVE is a very important technique for massive hepatic resection. Percutaneous trans-hepatic approach has the potential to damage vessels, bile duct, normal liver. Venous approaches, including via ICV, have the potential to damage vessels. In this case, we performed PVE from the IMV because we thought this approach would reduce the risk of complications. The patient successfully underwent PVE without complications. CONCLUSION PVE via IMV was successfully performed without complications. In multiple cancers case, this approach would be better approach than any other PVE approach like this case.
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Affiliation(s)
- Shoryu Takayama
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan.
| | - Kioto Yokoyama
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan
| | - Ken Ishikawa
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan
| | - Keisuke Tomoda
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan
| | - Hiroto Suzuki
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan
| | - Satoru Takayama
- Department of Surgery, Nagoya Tokushukai General Hospital, 2-52, Kozojicho-kita, Kasugai-Shi, Aichi 487-0016, Japan
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15
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Khuntikeo N, Pugkhem A, Srisuk T, Luvira V, Titapun A, Tipwaratorn T, Thanasukarn V, Klungboonkrong V, Wongwiwatchai J. Surgery. Recent Results Cancer Res 2023; 219:147-222. [PMID: 37660334 DOI: 10.1007/978-3-031-35166-2_7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
This chapter provides a comprehensive background from basic to applied knowledge of surgical anatomy which is necessary for the surgical treatment of cholangiocarcinoma (CCA) patients. Significant advances that have been made in the surgical treatment of CCA were examined. For instance, in-depth details are provided for appropriate preoperative assessment and treatment to optimize patient status and to improve the outcome of surgical treatment(s). Comprehensive details are provided for the surgical techniques and outcomes of treatments for each type of CCA with clear illustrations and images. This chapter also describes the role of minimally invasive surgery and liver transplantation in CCA treatment.
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Affiliation(s)
- Narong Khuntikeo
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand.
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand.
| | - Ake Pugkhem
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Tharatip Srisuk
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vor Luvira
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Attapol Titapun
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Theerawee Tipwaratorn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vasin Thanasukarn
- Department of Surgery, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Vivian Klungboonkrong
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
| | - Jitraporn Wongwiwatchai
- Department of Radiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, 40002, Thailand
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16
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Coskun N, Yildirim A, Yuksel AO, Canyigit M, Ozdemir E. The Radiation Dose Absorbed by Healthy Parenchyma Is a Predictor for the Rate of Contralateral Hypertrophy After Unilobar Radioembolization of the Right Liver. Nucl Med Mol Imaging 2022; 56:291-298. [PMID: 36425272 PMCID: PMC9679057 DOI: 10.1007/s13139-022-00770-6] [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: 06/06/2022] [Revised: 07/28/2022] [Accepted: 08/15/2022] [Indexed: 11/27/2022] Open
Abstract
Purpose To investigate the predictors of contralateral hypertrophy in patients treated with unilobar transarterial radioembolization (TARE) with yttrium-90-loaded resin microspheres due to unresectable right-liver tumors. Methods Patients who underwent right unilobar TARE with resin microspheres between May 2019 and September 2021 were screened retrospectively. Contralateral hypertrophy was evaluated by calculating the kinetic growth rate (KGR) in 8-10 weeks after TARE. The predictors of increased KGR were determined with linear regression analysis. Results A total of 24 patients (16 with primary and 8 with metastatic liver tumors) were included in the study. After right unilobar TARE, mean volume of the left lobe increased from 368.26 to 436.16 mL, while the mean volume of the right lobe decreased from 1576.22 to 1477.89 mL. The median KGR of the left lobe was 0.28% per week. The radiation dose absorbed by the healthy parenchyma of the right lobe was significantly higher in patients with increased KGR (31.62 vs. 18.78 Gy, p = 0.037). Linear regression analysis showed that the dose absorbed by healthy parenchyma was significantly associated with increased KGR (b = 0.014, p = 0.043). Conclusion Patients who received right unilobar TARE for liver malignancies could develop a substantial contralateral hypertrophy, and the radiation dose absorbed by the healthy parenchyma of the right lobe was significantly associated with increased KGR in the left lobe. TARE could have a role for inducing contralateral hypertrophy as it offers the advantage of concurrent local tumor control along with its hypertrophic effect.
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Affiliation(s)
- Nazim Coskun
- Department of Nuclear Medicine, Ankara City Hospital, Ankara, Turkey
| | - Aslihan Yildirim
- Department of Nuclear Medicine, Ankara City Hospital, Ankara, Turkey
| | | | - Murat Canyigit
- Department of Radiology, Ankara Yildirim Beyazit University, Ankara, Turkey
| | - Elif Ozdemir
- Department of Nuclear Medicine, Ankara City Hospital, Ankara, Turkey
- Department of Nuclear Medicine, Ankara Yildirim Beyazit University, Ankara, Turkey
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17
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Okada M, Ihara K, Miyoshi K, Nakao S, Tanabe M, Tokumitsu Y, Harada E, Sakamoto K, Nagano H, Ito K. Portal vein embolization via the ipsilateral percutaneous transhepatic approach versus laparotomic transileocecal approach: complications, profile and changes in future liver remnant volume. Br J Radiol 2022; 95:20210854. [PMID: 35348358 PMCID: PMC10996331 DOI: 10.1259/bjr.20210854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 03/20/2022] [Accepted: 03/22/2022] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVE Major liver resection is an effective treatment option for patients with liver malignancy. The future liver remnant (FLR) volume and complications after portal vein embolization (PVE) were compared between the ipsilateral right portal vein (PTPE) and transileocolic (TIPE) approaches. METHODS A total of 42 patients (TIPE, n = 22; PTPE, n = 20) underwent right lobectomy after PVE. CT and hepatobiliary scintigraphy were repeated before and after PVE. The blood examination findings and the FLR values (FLRCT: calculated from CT, %FLRCT: FLRCT ratio, %FLRSPECT: FLR ratio using single photon emission CT, FLRCT/BS: FLRCT to body surface ratio) were compared between two approach sites. The complications and mortality were also analyzed after PVE and major right hepatectomy. RESULTS There were no significant differences in the patient characteristics, blood examination findings or FLR values between two groups. Adequate liver regeneration was observed without significant differences between PTPE and TIPE (increased ratio of FLRCT: 8.7% vs 19.2%, p = 0.15 [25-75 percentile: 17.1-60.4], %FLRCT: 11.2% vs 8.3%, p = 0.25 [6.3-13.3], %FLRSPECT: 15.4% vs 19.2%, p = 0.09 [16.0-22.4], FLRCT/BS: 33.6% vs 47.1%, p = 0.19 [17.2-60.4], respectively), but TIPE required a significantly longer procedure time than PTPE [181.4 min vs 108.7 min, p < 0.01 (103.3-193.5)]. However, one patient was converted to TIPE due to bleeding during PTPE. After right lobectomy, portal vein stenosis or thrombosis was noted in three patients [two with TIPE (9.1%) and one with PTPE (5%)] and three TIPE patients died within 90 days (13.6%) after right hepatectomy. CONCLUSION FLR volume significantly increased after PVE, regardless of the approach sites; however, PTPE is a useful technique with a shorter procedure time.
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Affiliation(s)
- Munemasa Okada
- Department of Radiology, National Hospital Organization, Kanmon
Medical Center, Shimonoseki,
Japan
| | - Kenichiro Ihara
- Department of Radiology, Yamaguchi University Graduate School
of Medicine, Ube,
Japan
| | - Keisuke Miyoshi
- Department of Radiology, Yamaguchi University Graduate School
of Medicine, Ube,
Japan
| | - Sei Nakao
- Department of Surgery and Clinical Science, Yamaguchi
University Graduate School of Medicine,
Ube, Japan
| | - Masahiro Tanabe
- Department of Radiology, Yamaguchi University Graduate School
of Medicine, Ube,
Japan
| | - Yukio Tokumitsu
- Department of Gastroenterological, Breast and Endocrine
Surgery, Yamaguchi University Graduate School of Medicine,
Ube, Japan
| | - Eijiro Harada
- Department of Surgery and Clinical Science, Yamaguchi
University Graduate School of Medicine,
Ube, Japan
| | - Kazuhiko Sakamoto
- Department of Surgery, National Hospital Organization, Kanmon
Medical Center, Shimonoseki,
Japan
| | - Hiroaki Nagano
- Department of Gastroenterological, Breast and Endocrine
Surgery, Yamaguchi University Graduate School of Medicine,
Ube, Japan
| | - Katsuyoshi Ito
- Department of Radiology, Yamaguchi University Graduate School
of Medicine, Ube,
Japan
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Ellis RJ, Soares KC, Jarnagin WR. Preoperative Management of Perihilar Cholangiocarcinoma. Cancers (Basel) 2022; 14:cancers14092119. [PMID: 35565250 PMCID: PMC9104035 DOI: 10.3390/cancers14092119] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 04/19/2022] [Accepted: 04/21/2022] [Indexed: 02/01/2023] Open
Abstract
Perihilar cholangiocarcinoma is a rare hepatobiliary malignancy that requires thoughtful, multidisciplinary evaluation in the preoperative setting to ensure optimal patient outcomes. Comprehensive preoperative imaging, including multiphase CT angiography and some form of cholangiographic assessment, is key to assessing resectability. While many staging systems exist, the Blumgart staging system provides the most useful combination of resectability assessment and prognostic information for use in the preoperative setting. Once resectability is confirmed, volumetric analysis should be performed. Upfront resection without biliary drainage or portal venous embolization may be considered in patients without cholangitis and an estimated functional liver remnant (FLR) > 40%. In patients with FLR < 40%, judicious use of biliary drainage is advised, with the goal of selective biliary drainage of the functional liver remnant. Percutaneous biliary drainage may avoid inadvertent contamination of the contralateral biliary tree and associated infectious complications, though the relative effectiveness of percutaneous and endoscopic techniques is an ongoing area of study and debate. Patients with low FLR also require intervention to induce hypertrophy, most commonly portal venous embolization, in an effort to reduce the rate of postoperative liver failure. Even with extensive preoperative workup, many patients will be found to have metastatic disease at exploration and diagnostic laparoscopy may reduce the rate of non-therapeutic laparotomy. Management of perihilar cholangiocarcinoma continues to evolve, with ongoing efforts to improve preoperative liver hypertrophy and to further define the role of transplantation in disease management.
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Affiliation(s)
- Ryan J. Ellis
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (R.J.E.); (K.C.S.)
| | - Kevin C. Soares
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (R.J.E.); (K.C.S.)
- Department of Surgery, Weill Cornell Medical College, New York, NY 10021, USA
| | - William R. Jarnagin
- Hepatopancreatobiliary Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (R.J.E.); (K.C.S.)
- Department of Surgery, Weill Cornell Medical College, New York, NY 10021, USA
- Correspondence:
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19
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Degrauwe N, Duran R, Melloul E, Halkic N, Demartines N, Denys A. Induction of Robust Future Liver Remnant Hypertrophy Before Hepatectomy With a Modified Liver Venous Deprivation Technique Using a Trans-venous Access for Hepatic Vein Embolization. FRONTIERS IN RADIOLOGY 2021; 1:736056. [PMID: 37492178 PMCID: PMC10365094 DOI: 10.3389/fradi.2021.736056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Accepted: 10/19/2021] [Indexed: 07/27/2023]
Abstract
Purpose: Hepatic and/or portal vein embolization are performed before hepatectomy for patients with insufficient future liver remnant and usually achieved with a trans-hepatic approach. The aim of the present study is to describe a modified trans-venous liver venous deprivation technique (mLVD), avoiding the potential risks and limitations of a percutaneous approach to hepatic vein embolization, and to assess the safety, efficacy, and surgical outcome after mLVD. Materials and Methods: Retrospective single-center institutional review board-approved study. From March 2016 to June 2019, consecutive oncologic patients with combined portal and hepatic vein embolization were included. CT volumetric analysis was performed before and after mLVD to assess liver hypertrophy. Complications related to mLVD and surgical outcome were obtained from medical records. Results: Thirty patients (62.7 ± 14.5 years old, 20 men) with liver metastasis (60%) or primary liver cancer (40%) underwent mLVD. Twenty-one patients (70%) had hepatic vein anatomic variants. Technical success of mLVD was 100%. Four patients had complications (three minor and one major). FLR hypertrophy was 64.2% ± 51.3% (mean ± SD). Twenty-four patients (80%) underwent the planned hepatectomy and no surgery was canceled as a consequence of mLVD complications or insufficient hypertrophy. Fifty percent of patients (12/24) had no or mild complications after surgery (Clavien-Dindo 0-II), and 45.8% (11/24) had more serious complications (Clavien-Dindo III-IV). Thirty-day mortality was 4.2% (1/24). Conclusion: mLVD is an effective method to induce FLR hypertrophy. This technique is applicable in a wide range of oncologic situations and in patients with complex right liver vein anatomy.
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Affiliation(s)
- Nils Degrauwe
- Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Rafael Duran
- Department of Diagnostic Radiology and Interventional Radiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
| | - Emmanuel Melloul
- Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | - Nermin Halkic
- Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
| | | | - Alban Denys
- Department of Diagnostic Radiology and Interventional Radiology, Lausanne University Hospital (CHUV), Lausanne, Switzerland
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20
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Fan S. Liver injury during hepatectomy. SURGICAL PRACTICE 2021. [DOI: 10.1111/1744-1633.12532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Sheung‐tat Fan
- Liver Surgery and Transplant Centre Hong Kong Sanatorium and Hospital Happy Valley Hong Kong
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21
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Radulova-Mauersberger O, Weitz J, Riediger C. Vascular surgery in liver resection. Langenbecks Arch Surg 2021; 406:2217-2248. [PMID: 34519878 PMCID: PMC8578135 DOI: 10.1007/s00423-021-02310-w] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Accepted: 08/18/2021] [Indexed: 01/04/2023]
Abstract
Vascular surgery in liver resection is a standard part of liver transplantation, but is also used in oncological liver surgery. Malignant liver tumors with vascular involvement have a poor prognosis without resection. Surgery is currently the only treatment to provide long-term survival in advanced hepatic malignancy. Even though extended liver resections are increasingly performed, vascular involvement with need of vascular reconstruction is still considered a contraindication for surgery in many institutions. However, vascular resection and reconstruction in liver surgery-despite being complex procedures-are safely performed in specialized centers. The improvements of the postoperative results with reduced postoperative morbidity and mortality are a result of rising surgical and anesthesiological experience and advancements in multimodal treatment concepts with preconditioning measures regarding liver function and systemic treatment options. This review focuses on vascular surgery in oncological liver resections. Even though many surgical techniques were developed and are also used during liver transplantation, this special procedure is not particularly covered within this review article. We provide a summary of vascular reconstruction techniques in oncological liver surgery according to the literature and present also our own experience. We aim to outline the current advances and standards in extended surgical procedures for liver tumors with vascular involvement established in specialized centers, since curative resection improves long-term survival and shifts palliative concepts to curative therapy.
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Affiliation(s)
- Olga Radulova-Mauersberger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany.
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany.
- German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany.
| | - Jürgen Weitz
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
| | - Carina Riediger
- Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstraße 74, 01307, Dresden, Germany
- National Center for Tumor Diseases (NCT/UCC), Dresden, Germany
- German Cancer Research Center (DKFZ), Heidelberg, Germany
- Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
- Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany
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22
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Qadan M, Fong ZV, Delman AM, Gabr A, Salem R, Shah SA. Review of Use of Y90 as a Bridge to Liver Resection and Transplantation in Hepatocellular Carcinoma. J Gastrointest Surg 2021; 25:2690-2699. [PMID: 34345997 DOI: 10.1007/s11605-021-05095-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/07/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND The incidence of hepatocellular carcinoma (HCC) has been rising, and 80% of HCCs are unresectable at the time of presentation. In recent years, Yttrium-90 (Y90) radioembolization has arisen as a potential tool to treat the primary HCC tumor while also inducing contralateral liver hypertrophy to increase future liver remnant volumes. The goal of this multidisciplinary review is to summarize the contemporary evidence on the safety, efficacy, and utility of Y90 as a bridge to liver resection and transplant in patients with HCC. METHODS A narrative review was conducted of the recent literature regarding the utilization of Y90 as a therapy prior to liver resection or transplant in patients with HCC. A specific emphasis was placed on articles published in the last 10 years. RESULTS Y90 radioembolization has demonstrated a high safety profile and increasing utility in bridging and downstaging patients with HCC who subsequently undergo liver resection or transplant. The continuous advancements in treatment strategies and radiation dosimetry have paved the way for the incorporation of Y90 in all stages of HCC with different intents, including downstaging and bridging. CONCLUSIONS Y90 radioembolization can be safely used in the HCC population to bridge patients to resection or transplantation, induce future liver remnant growth, and select for less aggressive tumor biology prior to surgery.
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Affiliation(s)
- Motaz Qadan
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Zhi Ven Fong
- Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Aaron M Delman
- Department of Surgery, University of Cincinnati College of Medicine Medical Sciences Building, Room 1555, 231, Sabin Way Cincinnati, Albert, OH, 45267, USA
| | - Ahmed Gabr
- Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Riad Salem
- Department of Radiology, Northwestern Feinberg School of Medicine, Chicago, IL, USA
| | - Shimul A Shah
- Department of Surgery, University of Cincinnati College of Medicine Medical Sciences Building, Room 1555, 231, Sabin Way Cincinnati, Albert, OH, 45267, USA.
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23
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Yoo C, Shin SH, Park JO, Kim KP, Jeong JH, Ryoo BY, Lee W, Song KB, Hwang DW, Park JH, Lee JH. Current Status and Future Perspectives of Perioperative Therapy for Resectable Biliary Tract Cancer: A Multidisciplinary Review. Cancers (Basel) 2021; 13:cancers13071647. [PMID: 33916008 PMCID: PMC8037230 DOI: 10.3390/cancers13071647] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Revised: 03/27/2021] [Accepted: 03/27/2021] [Indexed: 12/13/2022] Open
Abstract
Simple Summary For decades, there has been no globally accepted neoadjuvant or adjuvant therapy in resectable biliary tract cancer. Based on the results of the BILCAP trial, adjuvant capecitabine has been widely regarded as standard adjuvant therapy. Focusing on the management of resectable biliary tract cancer, this article reviews each therapeutic strategy including surgery, chemotherapy and radiotherapy, and summarises published and ongoing clinical trials of neoadjuvant and adjuvant therapy. Abstract Biliary tract cancers (BTCs) are a group of aggressive malignancies that arise from the bile duct and gallbladder. BTCs include intrahepatic cholangiocarcinoma (IH-CCA), extrahepatic cholangiocarcinoma (EH-CCA), and gallbladder cancer (GBCA). BTCs are highly heterogeneous cancers in terms of anatomical, clinical, and pathological characteristics. Until recently, the treatment of resectable BTC, including surgery, adjuvant chemotherapy, and radiation therapy, has largely been based on institutional practice guidelines and evidence from small retrospective studies. Recently, several large randomized prospective trials have been published, and there are ongoing randomized trials for resectable BTC. In this article, we review prior and recently updated evidence regarding surgery, adjuvant and neoadjuvant chemotherapy, and adjuvant radiation therapy for patients with resectable BTC.
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Affiliation(s)
- Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-P.K.); (J.H.J.); (B.-Y.R.)
- Correspondence: (C.Y.); (J.H.L.); Tel.: +82-2-3010-1727 (C.Y.); +82-2-3010-1521 (J.H.L.)
| | - Sang Hyun Shin
- Department of Surgery, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea;
| | - Joon-Oh Park
- Division of Hematology and Oncology, Department of Internal Medicine, Samsung Medical Center, School of Medicine, Sungkyunkwan University, Seoul 06351, Korea;
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-P.K.); (J.H.J.); (B.-Y.R.)
| | - Jae Ho Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-P.K.); (J.H.J.); (B.-Y.R.)
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea; (K.-P.K.); (J.H.J.); (B.-Y.R.)
| | - Woohyung Lee
- Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea; (W.L.); (K.-B.S.); (D.-W.H.)
| | - Ki-Byung Song
- Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea; (W.L.); (K.-B.S.); (D.-W.H.)
| | - Dae-Wook Hwang
- Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea; (W.L.); (K.-B.S.); (D.-W.H.)
| | - Jin-hong Park
- Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea;
| | - Jae Hoon Lee
- Department of Surgery, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Korea; (W.L.); (K.-B.S.); (D.-W.H.)
- Correspondence: (C.Y.); (J.H.L.); Tel.: +82-2-3010-1727 (C.Y.); +82-2-3010-1521 (J.H.L.)
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24
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Induction of liver hypertrophy for extended liver surgery and partial liver transplantation: State of the art of parenchyma augmentation-assisted liver surgery. Langenbecks Arch Surg 2021; 406:2201-2215. [PMID: 33740114 PMCID: PMC8578101 DOI: 10.1007/s00423-021-02148-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Accepted: 03/03/2021] [Indexed: 12/17/2022]
Abstract
Background Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25–30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure. Purpose The aim of this review is to depict the various interventions for liver parenchyma augmentation–assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates. Conclusions To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly “palliative” disease into a curative and sometimes in a “chronic” disease.
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25
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Kwan J, Pua U. Review of Intra-Arterial Therapies for Colorectal Cancer Liver Metastasis. Cancers (Basel) 2021; 13:cancers13061371. [PMID: 33803606 PMCID: PMC8003062 DOI: 10.3390/cancers13061371] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 03/14/2021] [Accepted: 03/15/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary Colorectal cancer liver metastasis occurs in more than 50% of patients with colorectal cancer and is thought to be the most common cause of death from this cancer. The mainstay of treatment for inoperable liver metastasis has been combination systemic chemotherapy with or without the addition of biological targeted therapy with a goal for disease downstaging, for potential curative resection, or more frequently, for disease control. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies including hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are alternative treatment strategies that have shown promising results, most commonly in the salvage setting in patients with chemo-refractory disease. In recent years, their role in the first-line setting in conjunction with concurrent systemic chemotherapy has also been explored. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future. Abstract The liver is frequently the most common site of metastasis in patients with colorectal cancer, occurring in more than 50% of patients. While surgical resection remains the only potential curative option, it is only eligible in 15–20% of patients at presentation. In the past two decades, major advances in modern chemotherapy and personalized biological agents have improved overall survival in patients with unresectable liver metastasis. For patients with dominant liver metastatic disease or limited extrahepatic disease, liver-directed intra-arterial therapies such as hepatic arterial chemotherapy infusion, chemoembolization and radioembolization are treatment strategies which are increasingly being considered to improve local tumor response and to reduce systemic side effects. Currently, these therapies are mostly used in the salvage setting in patients with chemo-refractory disease. However, their use in the first-line setting in conjunction with systemic chemotherapy as well as to a lesser degree, in a neoadjuvant setting, for downstaging to resection have also been investigated. Furthermore, some clinicians have considered these therapies as a temporizing tool for local disease control in patients undergoing a chemotherapy ‘holiday’ or acting as a bridge in patients between different lines of systemic treatment. This review aims to provide an update on the current evidence regarding liver-directed intra-arterial treatment strategies and to discuss potential trends for the future.
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26
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Grisanti F, Prieto E, Bastidas JF, Sancho L, Rodrigo P, Beorlegui C, Iñarrairaegui M, Bilbao JI, Sangro B, Rodríguez-Fraile M. 3D voxel-based dosimetry to predict contralateral hypertrophy and an adequate future liver remnant after lobar radioembolization. Eur J Nucl Med Mol Imaging 2021; 48:3048-3057. [PMID: 33674893 DOI: 10.1007/s00259-021-05272-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 02/17/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION Volume changes induced by selective internal radiation therapy (SIRT) may increase the possibility of tumor resection in patients with insufficient future liver remnant (FLR). The aim was to identify dosimetric and clinical parameters associated with contralateral hepatic hypertrophy after lobar/extended lobar SIRT with 90Y-resin microspheres. MATERIALS AND METHODS Patients underwent 90Y PET/CT after lobar or extended lobar (right + segment IV) SIRT. 90Y voxel dosimetry was retrospectively performed (PLANET Dose; DOSIsoft SA). Mean absorbed doses to tumoral/non-tumoral-treated volumes (NTL) and dose-volume histograms were extracted. Clinical variables were collected. Patients were stratified by FLR at baseline (T0-FLR): < 30% (would require hypertrophy) and ≥ 30%. Changes in volume of the treated, non-treated liver, and FLR were calculated at < 2 (T1), 2-5 (T2), and 6-12 months (T3) post-SIRT. Univariable and multivariable regression analyses were performed to identify predictors of atrophy, hypertrophy, and increase in FLR. The best cut-off value to predict an increase of FLR to ≥ 40% was defined using ROC analysis. RESULTS Fifty-six patients were studied; most had primary liver tumors (71.4%), 40.4% had cirrhosis, and 39.3% had been previously treated with chemotherapy. FLR in patients with T0-FLR < 30% increased progressively (T0: 25.2%; T1: 32.7%; T2: 38.1%; T3: 44.7%). No dosimetric parameter predicted atrophy. Both NTL-Dmean and NTL-V30 (fraction of NTL exposed to ≥ 30 Gy) were predictive of increase in FLR in patients with T0 FLR < 30%, the latter also in the total cohort of patients. Hypertrophy was not significantly associated with tumor dose or tumor size. When ≥ 49% of NTL received ≥ 30 Gy, FLR increased to ≥ 40% (accuracy: 76.4% in all patients and 80.95% in T0-FLR < 30% patients). CONCLUSION NTL-Dmean and NTL exposed to ≥ 30 Gy (NTL-V30) were most significantly associated with increase in FLR (particularly among patients with T0-FLR < 30%). When half of NTL received ≥ 30 Gy, FLR increased to ≥ 40%, with higher accuracy among patients with T0-FLR < 30%.
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Affiliation(s)
- Fabiana Grisanti
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain.
| | - Elena Prieto
- Department of Medical Physics, Clínica Universidad de Navarra, Pamplona, Spain
| | | | - Lidia Sancho
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Madrid, Spain
| | - Pablo Rodrigo
- Department of Nuclear Medicine, Clínica Universidad de Navarra, Pamplona, Spain
| | | | | | | | - Bruno Sangro
- Liver Unit, Clínica Universidad de Navarra-IDISNA and CIBEREHD, Pamplona, Spain
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Bekki Y, Marti J, Toshima T, Lewis S, Kamath A, Argiriadi P, Simpson W, Facciuto L, Patel RS, Gunasekaran G, Kim E, Schiano TD, Facciuto ME. A comparative study of portal vein embolization versus radiation lobectomy with Yttrium-90 micropheres in preparation for liver resection for initially unresectable hepatocellular carcinoma. Surgery 2021; 169:1044-1051. [PMID: 33648768 DOI: 10.1016/j.surg.2020.12.012] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/07/2020] [Accepted: 12/09/2020] [Indexed: 12/19/2022]
Abstract
BACKGROUND Portal vein embolization before liver resection is considered the therapy of choice for patients with inadequate future liver remnants. The concept of radioembolization with Yttrium-90 to achieve the same goal has limited data. METHODS We retrospectively compared patients who underwent portal vein embolization and Yttrium-90 lobectomy before resection of hepatocellular carcinoma in patients with chronic liver disease. RESULTS Seventy-three patients underwent portal vein embolization and 22 patients underwent Yttrium-90. Forty-seven percent of patients before portal vein embolization required additional procedures for tumor control, and 27% of patients after Yttrium-90 required additional procedure to mainly induce further hypertrophy. Both therapies achieved the goal of future liver remnants >40%, but the degree of hypertrophy was significantly higher in Yttrium-90 patients (63% for Yttrium-90, 36% for portal vein embolization, P < .01). Tumor response was significantly better with Yttrium-90, achieving complete response in 50% of patients. Resectability rate was higher after portal vein embolization (85% for portal vein embolization, 64% for Yttrium-90, P = .03). Tumor progression was the most common reason precluding surgery. Complete tumor control was the reason not to pursue surgery in 18% of patients after Yttrium-90. CONCLUSION Both preoperative portal vein embolization and Yttrium-90, increases liver resectability rates by inducing hypertrophy of future liver remnants in patients with hepatocellular carcinoma and chronic liver disease. Yttrium-90 lobectomy achieved better tumor control and provided more time to assess therapy response, optimizing the indication for surgery.
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Affiliation(s)
- Yuki Bekki
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Josep Marti
- Department of Surgery, Centre Médico-Chirurgical de Tronquières, Aurillac, France
| | - Takeo Toshima
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Sara Lewis
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Amita Kamath
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Pamela Argiriadi
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - William Simpson
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Lucas Facciuto
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Rahul S Patel
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Ganesh Gunasekaran
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Edward Kim
- Department of Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Thomas D Schiano
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY
| | - Marcelo E Facciuto
- Recanati-Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
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Huang Y, Ge W, Kong Y, Ding Y, Gao B, Qian X, Wang W. Preoperative Portal Vein Embolization for Liver Resection: An updated meta-analysis. J Cancer 2021; 12:1770-1778. [PMID: 33613766 PMCID: PMC7890316 DOI: 10.7150/jca.50371] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 12/26/2020] [Indexed: 11/25/2022] Open
Abstract
Background: Portal vein embolization (PVE) is performed before major liver resection to increase liver volume remnant, controversy remains on the adverse effect of PVE on liver tumor patients. The current study highlighted the effect of PVE on the degree of hypertrophy of future liver remnant (FLR) and summarized PVE-related complications, aiming to provide a guideline for surgeons. Methods: A search of current published studies on PVE was performed. Meta-analysis was conducted to assess the effect of PVE on hypertrophy of FLR and summarized PVE-related complications. Results: 26 studies including 2335 patients were enrolled in the meta-analysis. All enrolled studies reported data regarding FLR hypertrophy rate, pooled effect size (ES) for FLR hypertrophy rate using a fixed-effect model was 0.105 (95%CI: 0.094-0.117, p=0.000), indicating PVE is favored in inducing FLR hypertrophy. Metatrim method indicated no obvious evidence of publication bias in the present meta-analysis. 247 (10.6%) patients exhibited PVE-related complications, receiving expectant treatment without affecting planned liver resection. Total 1782 patients (76%) underwent a subsequent liver resection after PVE, which is an encouraging result comparing with traditional resection rate in liver tumor patients. Conclusions: PVE is a safe and effective procedure with a low occurrence of related complications for inducing sufficient hypertrophy of FLR in liver tumor patients, which could elevate the resection rate of liver tumor patients. Careful patient cohort selection is crucial to avoid overuse of PVE in technically resectable patients. Further multiple central clinical trials are conducive to select optimal patient cohorts and provide a guideline for surgeons.
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Affiliation(s)
- Yu Huang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Wenhao Ge
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Yang Kong
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Bingqiang Gao
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Xiaohui Qian
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009.,Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou, Zhejiang 310009.,Research Center of Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou, Zhejiang 310009.,Clinical Medicine Innovation Center of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease of Zhejiang University, Hangzhou, Zhejiang 310009.,Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310009
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29
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Issues to be considered to address the future liver remnant prior to major hepatectomy. Surg Today 2020; 51:472-484. [PMID: 32894345 DOI: 10.1007/s00595-020-02088-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/08/2020] [Indexed: 02/08/2023]
Abstract
An accurate preoperative evaluation of the hepatic function and application of portal vein embolization in selected patients have helped improve the safety of major hepatectomy. In planning major hepatectomy, however, several issues remain to be addressed. The first is which cut-off values for serum total bilirubin level and prothrombin time should be used to define post-hepatectomy liver failure. Other issues include what minimum future liver remnant (FLR) volume is required; whether the total liver volume measured using computed tomography or the standard liver volume calculated based on the body surface area should be used to assess the adequacy of the FLR volume; whether there is a discrepancy between the FLR volume and function during the recovery period after portal vein embolization or hepatectomy; and how best the function of a specific FLR can be assessed. Various studies concerning these issues have been reported with controversial results. We should also be aware that different strategies and management are required for different types of liver damage, such as cirrhosis in hepatocellular carcinoma, cholangitis in biliary tract cancer, and chemotherapy-induced hepatic injury.
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Abstract
Liver cancer is one of the top leading causes of mortality worldwide. Conventional imaging using contrast enhanced CT and MRI are currently the mainstay of oncologic imaging of the liver for the diagnosis and management of cancer. In the past two decades, especially since the advent of hybrid imaging in the form of PET/CT and SPECT/CT, molecular imaging has been increasingly utilized for oncologic imaging and the variety of radionuclide probes for imaging liver cancers have been expanding. Beyond the usual workhorse of FDG as an oncologic tracer, there is a growing body of evidence showing that radiolabeled choline tracers, C-11 acetate and other new novel tracers may have increasing roles to play for the imaging of liver tumors. On the therapy front, there have also been advances in recent times in terms of targeted therapies for both primary and secondary liver malignancies, particularly with transarterial radioembolization. The concept of theranostics can be applied to transarterial radioembolization by utilizing a pretreatment planning scan, such as Tc-99m macroaggregated albumin scintigraphy, coupled with post treatment imaging. Radiation dose planning by personalized dosimetric calculations to the liver tumors is also being advocated. This article explores the general trends in the field of nuclear medicine for the imaging and treatment of liver cancer above and beyond routine diagnosis and management.
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Affiliation(s)
- Aaron Kian-Ti Tong
- Singapore General Hospital, Department of Nuclear Medicine and Molecular Imaging; DUKE-NUS Graduate Medical School, Singapore.
| | - Wei Ying Tham
- Singapore General Hospital, Department of Nuclear Medicine and Molecular Imaging; DUKE-NUS Graduate Medical School, Singapore
| | - Chow Wei Too
- Singapore General Hospital, Department of Vascular and Interventional Radiology; DUKE-NUS Graduate Medical School, Singapore
| | - David Wai-Meng Tai
- National Cancer Centre Singapore, Division of Medical Oncology; DUKE-NUS Graduate Medical School, Singapore
| | - Pierce Kah-Hoe Chow
- Singapore General Hospital, Department of Hepato-Pancreato-Biliary (HPB) and Transplant Surgery; National Cancer Centre Singapore, Division of Surgical Oncology; DUKE-NUS Graduate Medical School, Singapore
| | - David Chee-Eng Ng
- Singapore General Hospital, Department of Nuclear Medicine and Molecular Imaging; DUKE-NUS Graduate Medical School, Singapore
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Abbass MA, Slezak JM, Difronzo LA. Predictors of Early Postoperative Outcomes in 375 Consecutive Hepatectomies: A Single-institution Experience. Am Surg 2020. [DOI: 10.1177/000313481307901001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Although the safety of hepatic resection has improved, it is still a highly morbid procedure. A retrospective cohort of 375 patients undergoing hepatectomy (2004 to 2012) was done. All procedures were performed by a single surgeon at a tertiary center. To help identify trends over time, two subgroups were identified: Group 1 (n = 195 from October 2004 to December 2010) and Group 2 (n = 180 from January 2011 to November 2012). The two study groups had similar patient characteristics except there were more patients with cirrhosis in Group 2 (10 vs 17%, P = 0.04). A similar number of major hepatectomies was noted. Median estimated blood loss was 400 mL versus 300 mL ( P = 0.04) in Group 2. Overall complications were more common in Group 1 (54 vs 45%). Fewer Grade 3 or greater Clavien complications (22 vs 13%, P = 0.04) and fewer hospital readmissions were noted in Group 2 (20 vs 8%, P = 0.002). Morbidity was associated with worse Eastern Cooperative Oncology Group (ECOG) performance status, age older than 60 years, and open surgery. Grade 3 or greater Clavien complications were also associated with age older than 60 years, higher American Society of Anesthesiologists class, and worse ECOG status and median estimated blood less greater than 400 mL. Higher Model for End-stage Liver Disease score and advanced ECOG status were correlated with mortality. Outcomes of hepatic resection improved time despite more complex patient characteristics and an equal number of major hepatectomies being performed. However, worse ECOG performance status was a major predictor of postoperative complications and increased mortality.
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Affiliation(s)
| | - Jeffery M Slezak
- Department of Research and Evaluation, Kaiser Permanente, Pasadena, California
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32
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Kim D, Cornman-Homonoff J, Madoff DC. Preparing for liver surgery with "Alphabet Soup": PVE, ALPPS, TAE-PVE, LVD and RL. Hepatobiliary Surg Nutr 2020; 9:136-151. [PMID: 32355673 PMCID: PMC7188547 DOI: 10.21037/hbsn.2019.09.10] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 09/10/2019] [Indexed: 02/06/2023]
Abstract
Future liver remnant (FLR) size and function is a critical limiting factor for treatment eligibility and postoperative prognosis when considering surgical hepatectomy. Pre-operative portal vein embolization (PVE) has been proven effective in modulating FLR and now widely accepted as a standard of care. However, PVE is not always effective due to potentially inadequate augmentation of the FLR as well as tumor progression while awaiting liver growth. These concerns have prompted exploration of alternative techniques: associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), transarterial embolization-portal vein embolization (TAE-PVE), liver venous deprivation (LVD), and radiation lobectomy (RL). The article aims to review the principles and applications of PVE and these newer hepatic regenerative techniques.
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Affiliation(s)
- DaeHee Kim
- Department of Radiology, Division of Interventional Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joshua Cornman-Homonoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
| | - David C. Madoff
- Department of Radiology and Biomedical Imaging, Section of Interventional Radiology, Yale School of Medicine, New Haven, CT, USA
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Birgin E, Rasbach E, Seyfried S, Rathmann N, Diehl SJ, Schoenberg SO, Reissfelder C, Rahbari NN. Contralateral Liver Hypertrophy and Oncological Outcome Following Radioembolization with 90Y-Microspheres: A Systematic Review. Cancers (Basel) 2020; 12:cancers12020294. [PMID: 32012709 PMCID: PMC7072354 DOI: 10.3390/cancers12020294] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Revised: 01/17/2020] [Accepted: 01/23/2020] [Indexed: 02/06/2023] Open
Abstract
Radioembolization with 90Y-microspheres has been reported to induce contralateral liver hypertrophy with simultaneous ipsilateral control of tumor growth. The aim of the present systematic review was to summarize the evidence of contralateral liver hypertrophy and oncological outcome following unilateral treatment with radioembolization. A systematic literature search using the MEDLINE, EMBASE, and Cochrane libraries for studies published between 2008 and 2020 was performed. A total of 16 studies, comprising 602 patients, were included. The median kinetic growth rate per week of the contralateral liver lobe was 0.7% and declined slightly over time. The local tumor control was 84%. Surgical resection after radioembolization was carried out in 109 out of 362 patients (30%). Although the available data suggest that radioembolization prior to major hepatectomy is safe with a promising oncological outcome, the definitive role of radioembolization requires assessment within controlled clinical trials.
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Affiliation(s)
- Emrullah Birgin
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (E.B.); (E.R.); (S.S.); (C.R.)
| | - Erik Rasbach
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (E.B.); (E.R.); (S.S.); (C.R.)
| | - Steffen Seyfried
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (E.B.); (E.R.); (S.S.); (C.R.)
| | - Nils Rathmann
- Institute of Clinical Radiology and Nuclear Medicine, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (N.R.); (S.J.D.); (S.O.S.)
| | - Steffen J. Diehl
- Institute of Clinical Radiology and Nuclear Medicine, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (N.R.); (S.J.D.); (S.O.S.)
| | - Stefan O. Schoenberg
- Institute of Clinical Radiology and Nuclear Medicine, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (N.R.); (S.J.D.); (S.O.S.)
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (E.B.); (E.R.); (S.S.); (C.R.)
| | - Nuh N. Rahbari
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany; (E.B.); (E.R.); (S.S.); (C.R.)
- Correspondence: ; Tel.: +49-621-383-3591
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Campos S, Poley JW, van Driel L, Bruno MJ. The role of EUS in diagnosis and treatment of liver disorders. Endosc Int Open 2019; 7:E1262-E1275. [PMID: 31579708 PMCID: PMC6773586 DOI: 10.1055/a-0958-2183] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Accepted: 01/07/2019] [Indexed: 02/06/2023] Open
Abstract
Background and aim Transabdominal ultrasound (US), computed tomographic scanning (CT) and magnetic resonance imaging (MRI) are established diagnostic tools for liver diseases. Percutaneous transhepatic cholangiography is used to perform hepatic interventional procedures including biopsy, biliary drainage procedures, and radiofrequency ablation. Despite their widespread use, these techniques have limitations. Endoscopic ultrasound (EUS), a tool that has proven useful for evaluating the mediastinum, esophagus, stomach, pancreas, and biliary tract, has an expanding role in the field of hepatology complementing the traditional investigational modalities. This review aimed to assess the current scientific evidence regarding diagnostic and therapeutic applications of EUS for hepatic diseases.
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Affiliation(s)
- Sara Campos
- Department of Gastroenterology, Hospital Garcia da Orta, Portugal
- Department of Gastroenterology and Hepatology, Erasmus MC, The Netherlands
| | - Jan-Werner Poley
- Department of Gastroenterology and Hepatology, Erasmus MC, The Netherlands
| | - Lydi van Driel
- Department of Gastroenterology and Hepatology, Erasmus MC, The Netherlands
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus MC, The Netherlands
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Sugawara S, Arai Y, Sone M, Nara S, Kishi Y, Esaki M, Shimada K, Katai H. Retrospective Comparative Study of Absolute Ethanol with N-Butyl-2-Cyanoacrylate in Percutaneous Portal Vein Embolization. J Vasc Interv Radiol 2019; 30:1215-1222. [DOI: 10.1016/j.jvir.2018.12.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Revised: 12/08/2018] [Accepted: 12/17/2018] [Indexed: 12/12/2022] Open
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Collin Y, Paré A, Belblidia A, Létourneau R, Plasse M, Dagenais M, Turcotte S, Martel G, Roy A, Lapointe R, Vandenbroucke-Menu F. Portal vein embolization does not affect the long-term survival and risk of cancer recurrence among colorectal liver metastases patients: A prospective cohort study. Int J Surg 2018; 61:42-47. [PMID: 30537548 DOI: 10.1016/j.ijsu.2018.11.029] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 11/18/2018] [Accepted: 11/29/2018] [Indexed: 12/25/2022]
Abstract
BACKGROUND Previous studies comparing the survival outcomes of liver resections with and without preoperative portal vein embolization (PVE) for colorectal liver metastases (CLM) have linked PVE to higher rate of tumor progression, lower overall survival (OS) and lower disease-free survival (DFS). The lack of adjusted models to compare these outcomes is a limitation of these studies since patients requiring PVE may differ significantly from the ones receiving upfront surgery. MATERIALS AND METHODS Prospective cohort study of 128 patients undergoing CLM resection. The OS analysis followed an intent-to-treat (ITT) approach. The adjusted impact of PVE on OS and DFS was evaluated using multivariate Cox regression models. RESULTS Seventy-one patients underwent PVE before attempting a liver resection while 57 received upfront surgery (NoPVE). All NoPVE patients were resected while 14 PVE participants (19.7%) were not operated (tumor progression = 9/14). PVE patients had a significantly higher preoperative lesions count (3 [1.75-4] vs 1 [1-2.5]; p < 0.001), a higher prevalence of bilateral metastases (23.5% vs 8.8, p = 0.028) and a higher count of neo-adjuvant chemotherapy cycles compared to NoPVE patients. The OS of PVE patients was similar to NoPVE participants (44.7 months [26.9-69.5] vs 49.0 [24.9-64.8], p = 0.761). The DFS of resected PVE patients was higher than NoPVE patients (33.2 months [10.7-54.6] vs 23.4 months [14.1-58.1], p = 0.991). In the adjusted models, preoperative lesions count was the only significant predictor of overall mortality (HR+IC95 = 1.06 (1.02-1.11) p = 0.005) and cancer recurrence (HR+IC95 = 1.14 (1.03-1.27) p = 0.012). CONCLUSION In the context of CLM, patients requiring PVE differ significantly from patients receiving upfront surgery. This confirms the need for adjusted models when comparing the clinical outcomes of both groups. Our adjusted analysis suggests that PVE is not a significant predictor of a lower OS or DFS. PVE allowed the resection of 80% of participants with initially unresectable CLM. INSTITUTIONAL PROTOCOL NUMBER 12.106 STUDY REGISTRATION NUMBER: NCT03168230.
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Affiliation(s)
- Yves Collin
- Service de chirurgie générale, Département de chirurgie, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada
| | - Alex Paré
- Service de chirurgie générale, Département de chirurgie, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC, Canada.
| | - Assia Belblidia
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Richard Létourneau
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Marylène Plasse
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Michel Dagenais
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Simon Turcotte
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Guillaume Martel
- Hepato-Biliary and Pancreatic Surgery Service, Surgery Department, Ottawa Hospital, Ottawa, ON, Canada
| | - André Roy
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Real Lapointe
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
| | - Frank Vandenbroucke-Menu
- Service de chirurgie hépatobiliaire et pancréatique et de transplantation, Département de chirurgie, Centre Hospitalier de l'Université de Montréal, Site St-Luc, Montréal, QC, Canada
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Yim J, Hyun D, Cho SK, Park KB, Park HS, Shin SW, Choi DW, Kim S, Baek SY, Lee SY. Effect of Hyperbilirubinemia on Hepatic Hypertrophy after Portal Vein Embolization and Liver Failure after Hepatectomy in Primary Biliary Malignancy. J Vasc Interv Radiol 2018; 30:31-37. [PMID: 30527653 DOI: 10.1016/j.jvir.2018.08.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2018] [Revised: 08/04/2018] [Accepted: 08/04/2018] [Indexed: 10/27/2022] Open
Abstract
PURPOSE To retrospectively investigate the impact of hyperbilirubinemia on future liver remnant (FLR) volume after percutaneous transhepatic portal vein embolization (PVE) and incidence of post-hepatectomy liver failure in primary biliary malignancy. MATERIALS AND METHODS Eighty-seven patients (62 men, overall mean age 66.9 y) who underwent PVE, using Gelfoam and coils before major hepatectomy between January 2004 and June 2016, were included in this study and divided into a hyperbilirubinemia (serum total bilirubin level at PVE 5.80 ± 2.44 mg/dL; n = 41) group and a control group (1.09 ± 0.73 mg/dL; n = 46). Liver volume was measured from computerized tomographic data before and 18.5 days, on average, after PVE. Correlation between FLR hypertrophy (degree of hypertrophy and percentage increase in future liver remnant [%FLR]) and total bilirubin were analyzed. FLR hypertrophy and incidence of post-hepatectomy liver failure were compared. Simple and multiple regressions were used for univariable and multivariable analyses, respectively. RESULTS Mean FLR volumes before and after PVE were 529.1 cm3 and 640.5 cm3, respectively. Degree of hypertrophy and %FLR were 7.64 ± 4.22 and 21.77 ± 13.34, respectively. There was no significant correlation between FLR hypertrophy and total bilirubin (P > .5). FLR hypertrophy was not significantly different between the 2 groups. Planned major hepatectomy was performed in 73 patients (83.9%). Grade 3 post-hepatectomy liver failure occurred in 6 patients (8.2%; 2 in the hyperbilirubinemia group and 4 in the control group), and its incidence was not significantly different between the groups (P = .354). CONCLUSIONS Hyperbilirubinemia at the time of PVE seems to have no effect on FLR hypertrophy. The incidence of grade 3 post-hepatectomy liver failure is not likely to be influenced, either.
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Affiliation(s)
- Jaehyun Yim
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Dongho Hyun
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea.
| | - Sung Ki Cho
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Kwang Bo Park
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Hong Suk Park
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Sung Wook Shin
- Department of Radiology, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Dong Wook Choi
- Department of Surgery, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Seonwoo Kim
- Statistics and Data Center, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Sung-Young Baek
- Statistics and Data Center, Samsung Medical Center, 81 Irwon-Ro Gangnam-Gu, 06351, Seoul, Korea
| | - Sang Yub Lee
- Department of Radiology, Kyungpook National University School of Medicine, Daegu, Korea
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Ray S, Mehta N, Golhar A, Nundy S. Post hepatectomy liver failure - A comprehensive review of current concepts and controversies. Ann Med Surg (Lond) 2018; 34:4-10. [PMID: 30181871 PMCID: PMC6120608 DOI: 10.1016/j.amsu.2018.08.012] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/24/2018] [Accepted: 08/14/2018] [Indexed: 02/06/2023] Open
Abstract
Post hepatectomy liver failure (PHLF) comprises of a conundrum of symptoms and signs following major hepatic resections. The pathophysiology essentially revolves around disruption of the normal hepatocyte regeneration and disturbed liver homeostasis. Prompt identification of the pre-operative predictors of PHLF in the form of biochemical parameters and imaging features are of paramount importance for any hepatic surgeon and forms the cornerstone of its management. Treatment revolves around a goal-directed resuscitation of the systemic organ failure. Auxiliary support systems such as liver dialysis devices and stem cell therapy are still under investigational trials for treatment of the same. Orthotopic liver transplantation (OLT) is the last resort in most cases not responding to other measures.
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Affiliation(s)
- S. Ray
- Department of Surgical Gastroenterology and Liver Transplantation, Sir Ganga Ram Hospital, New Delhi, India
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Lidsky ME, Jarnagin WR. Surgical management of hilar cholangiocarcinoma at Memorial Sloan Kettering Cancer Center. Ann Gastroenterol Surg 2018; 2:304-312. [PMID: 30003193 PMCID: PMC6036362 DOI: 10.1002/ags3.12181] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2018] [Accepted: 05/20/2018] [Indexed: 02/06/2023] Open
Abstract
Hilar cholangiocarcinoma, which represents approximately 60% of biliary tract malignancies, is increasing in incidence and presents an ongoing challenge for patients and hepatobiliary surgeons. Although the majority of patients present with advanced disease, the remaining minority of patients are best treated with surgical resection or transplant. Transplant is typically reserved for locally unresectable tumors often in the setting of underlying hepatic dysfunction and will not be discussed herein. This review, therefore, focuses on oncological resection and the strategies implemented for the treatment of hilar cholangiocarcinoma at a quaternary referral center, including preoperative considerations such as patient selection and optimization of the future liver remnant, nuances to the operative approach for these tumors such as resection under low central venous pressure and management of the bile duct, as well as postoperative management.
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Affiliation(s)
- Michael E. Lidsky
- Department of SurgeryMemorial Sloan Kettering Cancer CenterNew YorkNYUSA
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40
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Jiang Z, Li C, Zhao Z, Liu Z, Guan X, Yang M, Li X, Yuan D, Qiu S, Wang X. Abnormal Liver Function Induced by Space-Occupying Lesions Is Associated with Unfavorable Oncologic Outcome in Patients with Colorectal Cancer Liver Metastases. BIOMED RESEARCH INTERNATIONAL 2018; 2018:9321270. [PMID: 29862297 PMCID: PMC5976940 DOI: 10.1155/2018/9321270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2017] [Revised: 01/25/2018] [Accepted: 02/27/2018] [Indexed: 02/06/2023]
Abstract
An early prediction of prognosis for patients with colorectal liver metastasis (CRLM) may help us determine treatment strategies. Liver function reflects the effect of the overall metastatic burden. We investigated the prognostic value of liver function in CRLM patients. In our study, patients with abnormal LFTs (liver function tests) had a poorer prognosis than did those with normal LFTs (P < 0.05). A multivariate analysis revealed that LFTs was an independent prognostic factor for CRLM. For those patients with abnormal LFTs, novel prognostic contour maps were generated using LFTs, and no positive correlation exists between the values of survival duration and abnormal LFTs. Additionally, the MTVR (metastatic tumor volume ratio) was measured directly by magnetic resonance imaging and was shown to be highly correlated to LFTs by a Pearson correlation analysis. A multivariate logistic regression analysis also demonstrated that the MTVR and hepatectomy were independently predictive of abnormal LFTs. The space-occupying effect of metastatic lesions can cause abnormal LFTs, resulting in a poor prognosis. Biochemical analyses of LFTs at the initial diagnosis of CRLM enable the stratification of patients into low- and high-risk groups; it may help clinicians determine promising treatment strategies.
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Affiliation(s)
- Zheng Jiang
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Chunxiang Li
- Department of Thoracic Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Zhixun Zhao
- Department of Colorectal Cancer Surgery, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Zheng Liu
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Xu Guan
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Ming Yang
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
| | - Xiaofu Li
- Department of Magnetic Resonance Imaging, The 2nd Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Dawei Yuan
- Genesis (Beijing) Co., Ltd., Beijing 100102, China
| | - Songbo Qiu
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA
| | - Xishan Wang
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China
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41
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Quinn LM, Dunne DFJ, Jones RP, Poston GJ, Malik HZ, Fenwick SW. Optimal perioperative care in peri-hilar cholangiocarcinoma resection. Eur Surg 2018; 50:93-99. [PMID: 29875797 PMCID: PMC5968056 DOI: 10.1007/s10353-018-0529-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 04/09/2018] [Indexed: 12/24/2022]
Abstract
Surgical resection remains the only proven curative treatment for peri-hilar cholangiocarcinoma. Despite recent advances in liver surgery techniques and perioperative care, resection for peri-hilar cholangiocarcinoma remains associated with significant morbidity and mortality. Considerable variation in the perioperative management of these patients exists. Optimal perioperative management has the potential to deliver improved outcomes. This article seeks to summarize the evidence underpinning best practice in the perioperative care of patients undergoing resection of peri-hilar cholangiocarcinoma. The authors also seek to identify areas where research efforts and future clinical trials should be targeted.
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Affiliation(s)
- Leonard M. Quinn
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
- Institute of translational Medicine, University of Liverpool, Ashton Street, L69 3GE Liverpool, UK
| | - Declan F. J. Dunne
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
| | - Robert P. Jones
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
| | - Graeme J. Poston
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
| | - Hassan Z. Malik
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
| | - Stephen W. Fenwick
- Liverpool Hepatobiliary Centre, Aintree University Hospital, Longmoor Lane, L9 7AL Liverpool, UK
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Teo JY, Allen JC, Ng DCE, Abdul Latiff JB, Choo SP, Tai DWM, Low ASC, Cheah FK, Chang JPE, Kam JH, Lee VTW, Chung AYF, Chan CY, Chow PKH, Goh BKP. Prospective study to determine early hypertrophy of the contra-lateral liver lobe after unilobar, Yttrium-90, selective internal radiation therapy in patients with hepatocellular carcinoma. Surgery 2018; 163:1008-1013. [PMID: 29306542 DOI: 10.1016/j.surg.2017.10.014] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/20/2017] [Accepted: 10/11/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND Liver resection is a major curative option in patients presenting with hepatocellular carcinoma. An inadequate functional liver remnant is a major limiting factor precluding liver resection. In recent years, hypertrophy of the functional liver remnant after selective internal radiation therapy hypertrophy has been observed, but the degree of hypertrophy in the early postselective internal radiation therapy period has not been well studied. METHODS We conducted a prospective study on patients undergoing unilobar, Yttrium-90 selective internal radiation therapy for hepatocellular carcinoma to evaluate early hypertrophy at 4-6 weeks and 8-12 weeks after selective internal radiation therapy. RESULTS In the study, 24 eligible patients were recruited and had serial volumetric measurements performed. The median age was 66 years (38-75 years). All patients were either Child-Pugh Class A or B, and 6/24 patients had documented, clinically relevant portal hypertension; 15 of the 24 patients were hepatitis B positive. At 4-6 weeks, modest hypertrophy was seen (median 3%; range -12 to 42%) and this increased at 8-12 weeks (median 9%; range -12 to 179%). No preprocedural factors predictive of hypertrophy were identified. CONCLUSION Hypertrophy of the functional liver remnant after selective internal radiation therapy with Yttrium-90 occurred in a subset of patients but was modest and unpredictable in the early stages. Selective internal radiation therapy cannot be recommended as a standard treatment modality to induce early hypertrophy for patients with hepatocellular carcinoma. (Surgery 2017;160:XXX-XXX.).
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Affiliation(s)
- Jin Yao Teo
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - John Carson Allen
- Office of Clinical Sciences, Duke-NUS Graduate Medical School Singapore, Singapore
| | - David Chee Eng Ng
- Department of Nuclear Medicine and PET, Singapore General Hospital, Singapore
| | | | - Su Pin Choo
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - David Wai-Meng Tai
- Department of Medical Oncology, National Cancer Centre Singapore, Singapore
| | | | - Foong Koon Cheah
- Department of Diagnostic Radiology, Singapore General Hospital, Singapore
| | - Jason Pik Eu Chang
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Juinn Huar Kam
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Victor T W Lee
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Alexander Yaw Fui Chung
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Chung Yip Chan
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Pierce Kah Hoe Chow
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - Brian K P Goh
- Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore.
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Watanabe N, Yamamoto Y, Sugiura T, Okamura Y, Ito T, Ashida R, Aramaki T, Uesaka K. A predictive scoring system for insufficient liver hypertrophy after preoperative portal vein embolization. Surgery 2018; 163:1014-1019. [PMID: 29501348 DOI: 10.1016/j.surg.2017.11.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2017] [Revised: 10/31/2017] [Accepted: 11/03/2017] [Indexed: 12/12/2022]
Abstract
BACKGROUND The factors which affect hypertrophy of the future liver remnant after portal vein embolization remain unclear. The aim of this study was to clarify the clinical factors affecting the hypertrophy rate after portal vein embolization and to develop a scoring system predicting insufficient liver hypertrophy. METHODS The cases of a total of 152 patients who underwent portal vein embolization of the right portal branch between 2006 and 2016 were reviewed retrospectively. The score to predict insufficient (<25%) hypertrophy was established based on logistic regression analyses of the clinical parameters before portal vein embolization. RESULTS After portal vein embolization, the future liver remnant volume, expressed as the median (range), significantly increased from 364 (151-801) mL, 33% (18%-54%), to 451 (242-866) mL, 42% (26%-65%). The median hypertrophy rate was 24% (-5% to 96%). A preoperative predictive scoring system for insufficient liver hypertrophy was constructed using the following 3 factors: an initial future liver remnant volume ≥35% (2 points), alkaline phosphatase ≥450 IU/dL (1 point), and cholinesterase <220 mg/dL (1 point). The constructed scoring system indicated the proportion of patients with insufficient liver hypertrophy (<25%) to be 6 out of 42 (14%) in the low-score group (0 points), 44 out of 77 (57%) in the medium-score group (1-2 points), and 30 out of 33 (91%) in the high-score group (3-4 points). The hypertrophy rate of future liver remnant was different among the 3 groups (low-score group, 38.9% [-2.4% to 81.4%]; medium-score group, 22.7% [-5.1% to 95.5%]; high-score group, 18.2% [2.4%-30.7%]) (P < .001). CONCLUSION The constructed scoring system was able to stratify patients before portal vein embolization according to the possibility of developing insufficient liver hypertrophy.
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Affiliation(s)
- Nobuyuki Watanabe
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yusuke Yamamoto
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan.
| | - Teiichi Sugiura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Yukiyasu Okamura
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takaaki Ito
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Ryo Ashida
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
| | - Takeshi Aramaki
- Division of Radiology, Shizuoka Cancer Center, Shizuoka, Japan
| | - Katsuhiko Uesaka
- Division of Hepato-Biliary-Pancreatic Surgery, Shizuoka Cancer Center, Shizuoka, Japan
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Khan AS, Garcia-Aroz S, Ansari MA, Atiq SM, Senter-Zapata M, Fowler K, Doyle MB, Chapman WC. Assessment and optimization of liver volume before major hepatic resection: Current guidelines and a narrative review. Int J Surg 2018; 52:74-81. [PMID: 29425829 DOI: 10.1016/j.ijsu.2018.01.042] [Citation(s) in RCA: 74] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 01/20/2018] [Accepted: 01/29/2018] [Indexed: 02/06/2023]
Abstract
Post hepatectomy liver failure (PHLF) remains a significant cause of morbidity and mortality after major liver resection. Although the etiology of PHLF is multifactorial, an inadequate functional liver remnant (FLR) is felt to be the most important modifiable predictor of PHLF. Pre-operative evaluation of FLR function and volume is of paramount importance before proceeding with any major liver resection. Patients with inadequate or borderline FLR volume must be considered for volume optimization strategies such as portal vein embolization (PVE), two stage hepatectomy with portal vein ligation (PVL), Yttrium-90 radioembolization, and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). This paper provides an overview of assessing FLR volume and function, and discusses indications and outcomes of commonly used volume optimization strategies.
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Affiliation(s)
- Adeel S Khan
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA.
| | - Sandra Garcia-Aroz
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA
| | | | - Syed M Atiq
- Sanford University of South Dakota Medical Center, Sioux Falls, SD, USA
| | - Michael Senter-Zapata
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA
| | - Kathryn Fowler
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA
| | - M B Doyle
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA
| | - W C Chapman
- Section of Transplant Surgery, Department of Surgery, Washington University in St. Louis, MO, USA
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Gupta M, Choudhury PS, Singh S, Hazarika D. Liver Functional Volumetry by Tc-99m Mebrofenin Hepatobiliary Scintigraphy before Major Liver Resection: A Game Changer. Indian J Nucl Med 2018; 33:277-283. [PMID: 30386047 PMCID: PMC6194760 DOI: 10.4103/ijnm.ijnm_72_18] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Future remnant liver function (FRL-F) estimation is important before major liver resection to avoid posthepatectomy liver failure (PHLF). Conventionally, it is estimated by global dynamic liver function tests which assume homogeneous liver function and unable to calculate regional function. Computed tomography is another method to estimate FRL volume but assumes that volume is equivalent to function. Hence, a global and regional non-invasive liver function test is desirable. Studies were identified by MEDLINE, PubMed, and Google Scholar for articles from January 1990 to December 2017 using the following keywords “Mebrofenin, hepatobiliary scintigraphy (HBS), FRL-F, PHLF, portal vein embolization (PVE).” HBS with technetium-99 m galactosyl human serum albumin (Tc-99m GSA) and Tc-99m Mebrofenin is a known test for functional liver assessment. Restricted availability of Tc-99m GSA only in Japan is a main drawback for its global acceptance. However, Tc-99m Mebrofenin is routinely available to the rest of the world. A unique protocol for FRL-F estimation by Tc-99m Mebrofenin is described in detail in this review. Tc-99m Mebrofenin HBS has shown a strong correlation to 15 min indocyanine green clearance. HBS has been reported better in predicting the risk of PHLF with a 2.69%/min/m2 cutoff of FRL-F. Tc-99m Mebrofenin HBS has been found better in stratification of PVE before major liver surgery as well. We concluded, Tc-99m Mebrofenin HBS was unique in calculating global and regional liver function and takes nonuniformity and underlying pathology in the account. Moreover, a single cutoff might fit in all for PHLF risk assessment and PVE stratification.
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Affiliation(s)
- Manoj Gupta
- Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Partha Sarathi Choudhury
- Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Shivendra Singh
- Department of GI and HPB Oncosurgery, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
| | - Dibyamohan Hazarika
- Department of Radiology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
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Reames BN, Pawlik TM. Hilar Cholangiocarcinoma. SURGICAL DISEASES OF THE PANCREAS AND BILIARY TREE 2018:345-389. [DOI: 10.1007/978-981-10-8755-4_14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Sun JH, Zhang YL, Nie CH, Li J, Zhou TY, Zhou GH, Zhu TY, Chen LM, Wang WL, Zheng SS. Effects of liver cirrhosis on portal vein embolization prior to right hepatectomy in patients with primary liver cancer. Oncol Lett 2017; 15:1411-1416. [PMID: 29434832 PMCID: PMC5777121 DOI: 10.3892/ol.2017.7530] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 05/08/2017] [Indexed: 12/12/2022] Open
Abstract
Preoperative portal vein embolization (PVE) induces compensatory hyperplasia of the future liver remnants (FLR), thus increasing resectability in the non-cirrhotic patients with primary liver cancer (PLC). However, it is unclear if it is similar in patients with liver cirrhosis. Therefore, the present study investigated the PVE value prior to liver resection in patients with PLC, and the liver cirrhotic effects on the compensatory hypertrophy of FLRs following PVE. In the present study, 21 patients with PLC who successfully underwent hepatic resection subsequent to PVE, were retrospectively examined. The patients were divided into a non-cirrhosis group and a cirrhosis group according to the absence or presence of cirrhosis, respectively. The FLR volume between the two groups of patients was compared. There was a significant difference in the FLR volume for all patients prior to, and 4–6 weeks following, PVE (P<0.001). PVE induced significant compensatory hypertrophy in the FLRs whether in the non-cirrhosis group (P=0.002) or cirrhosis group (P<0.001). However, no significant difference was identified between the two groups with respect to FLR volume enlargement 4–6 weeks following PVE (P=0.373). In conclusion, PVE prior to hepatectomy may promote FLR compensatory hypertrophy and an increase in the resectability of PLC tumors. No significant effects of liver cirrhosis were identified on liver lobe hyperplasia following PVE.
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Affiliation(s)
- Jun-Hui Sun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Yue-Lin Zhang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Chun-Hui Nie
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Ju Li
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Tan-Yang Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Guan-Hui Zhou
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Tong-Yin Zhu
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Li-Ming Chen
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Wei-Lin Wang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
| | - Shu-Sen Zheng
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China
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Ha HT, Han YS, Chun JM. Totally laparoscopic associating liver partition and portal vein ligation for staged hepatectomy using anterior approach in HCC patient with Type II portal vein anomaly: a case report. Ann Hepatobiliary Pancreat Surg 2017; 21:217-222. [PMID: 29264585 PMCID: PMC5736742 DOI: 10.14701/ahbps.2017.21.4.217] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 07/07/2017] [Indexed: 02/07/2023] Open
Abstract
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has gradually developed because of rapid hypertrophy of the future liver remnant volume (FLR) in spite of high morbidity. To minimize the patient's postoperative pain and morbidity including wound complication caused by two consecutive major abdominal operations, we adopted a totally laparoscopic approach and used a composite mesh graft. Also, to maximize the oncologic efficacy, we adopted the “anterior approach” technique. A 44-year-old woman with large hepatitis B-related hepatocellular carcinoma (HCC) in her right lobe was transferred to our hospital for surgical treatment. Preoperatively predicted FLR by a CT scan was 21% and type II portal vein anomaly was detected. A totally laparoscopic approach was planned. During the first stage operation, right anterior and posterior portal veins were meticulously dissected and tied. After parenchymal transection by the “anterior approach” technique, two glissonian pedicles of the right liver were individually isolated. A composite mesh graft was used to prevent severe adhesion on both liver partition surfaces. During the second-stage operation, 9 days after the first stage operation, the two isolated glissonian pedicles were initially transected. After full mobilization of the right lobe, the right hepatic vein was also transected. The right lobe was removed through the Pfannenstiel incision. She was discharged 7 days after the second stage operation. Her postoperative course was uneventful and there was no HCC recurrence for 15 months after hepatectomy. A totally laparoscopic ALPPS procedure can be a feasible technique that ensures patient safety and oncologic superiority, even in patients with complicated anatomical variation.
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Affiliation(s)
- Heon Tak Ha
- Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Young Seok Han
- Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
| | - Jae Min Chun
- Department of Surgery, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea
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Huang SY, Aloia TA. Portal Vein Embolization: State-of-the-Art Technique and Options to Improve Liver Hypertrophy. Visc Med 2017; 33:419-425. [PMID: 29344515 DOI: 10.1159/000480034] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Portal vein embolization (PVE) is associated with a high technical and clinical success rate for induction of future liver remnant hypertrophy prior to surgical resection. The degree of hypertrophy is variable and depends on multiple factors, including technical aspects of the procedure and underlying chronic liver disease. For patients with insufficient liver volume following PVE, adjunctive techniques, such as intra-portal administration of stem cells, dietary supplementation, transarterial embolization, and hepatic vein embolization, are available. Our purpose is to review the state-of-the-art technique associated with high-quality PVE and to discuss options to improve hypertrophy of the future liver remnant.
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Affiliation(s)
- Steven Y Huang
- Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Thomas A Aloia
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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50
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Huiskens J, Olthof PB, van der Stok EP, Bais T, van Lienden KP, Moelker A, Krumeich J, Roumen RM, Grünhagen DJ, Punt CJA, van Amerongen M, de Wilt JHW, Verhoef C, Van Gulik TM. Does portal vein embolization prior to liver resection influence the oncological outcomes - A propensity score matched comparison. Eur J Surg Oncol 2017; 44:108-114. [PMID: 29126672 DOI: 10.1016/j.ejso.2017.09.017] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 08/21/2017] [Accepted: 09/13/2017] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION There is an ongoing controversy surrounding portal vein embolization (PVE) regarding the short-term safety of PVE and long-term oncological benefit. This study aims to compare survival outcomes of patients subjected to major liver resection for colorectal liver metastases (CRLM) with or without PVE. METHODS All consecutive patients who underwent major liver resection for CRLM in four high volume liver centres between January 2000 and December 2015 were included. Major liver resection was defined as resection of at least three Couinaud liver segments. To reduce selection bias, propensity score matching was performed for PVE and non-PVE patients with overall and disease-free survival as primary endpoints. For matching, all patients who underwent PVE followed by a major liver resection were selected. Patients were matched to patients who had undergone major liver resection without PVE. RESULTS Of 745 patients undergoing major liver resection for CRLM, 53 patients (7%) underwent PVE before liver resection. In the overall cohorts, PVE patients had inferior DFS and a trend towards inferior OS. A total of 46 PVE patients were matched to 46 non-PVE patients to create comparable cohorts and between these two matched cohorts no differences in DFS (3-year DFS 16% vs 9%, p = 0.776) or OS (5-year OS 14% vs 14%, p = 0.866) were found. CONCLUSIONS This retrospective, matched analysis does not suggest a negative impact of PVE on long-term outcomes after liver resection in patients with CRLM.
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Affiliation(s)
- Joost Huiskens
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
| | - Pim B Olthof
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Eric P van der Stok
- Department of Surgical Oncology and Gastro Intestinal Surgery, ErasmusMC, Rotterdam, The Netherlands
| | - Thomas Bais
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Krijn P van Lienden
- Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Adriaan Moelker
- Department of Radiology, ErasmusMC, Rotterdam, The Netherlands
| | - Jan Krumeich
- Department of Surgical Oncology, Máxima Medical Center, Veldhoven, The Netherlands
| | - Rudi M Roumen
- Department of Surgical Oncology, Máxima Medical Center, Veldhoven, The Netherlands
| | - Dirk J Grünhagen
- Department of Surgical Oncology and Gastro Intestinal Surgery, ErasmusMC, Rotterdam, The Netherlands
| | - Cornelis J A Punt
- Department of Medical Oncology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Martin van Amerongen
- Department of Radiology, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands
| | - Johannes H W de Wilt
- Department of Surgery, Radboud University Medical Center, Radboud University, Nijmegen, The Netherlands
| | - Cornelis Verhoef
- Department of Surgical Oncology and Gastro Intestinal Surgery, ErasmusMC, Rotterdam, The Netherlands
| | - Thomas M Van Gulik
- Department of Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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