Research groups

GC18 Translational Research in Surgery of Solid Organ Transplantation

Our research group addresses all the specific research areas related to solid organ transplants that are carried out at the Hospital Universitario Reina Sofía: liver transplantation, pancreas transplantation, kidney transplantation, lung transplantation, and heart transplantation. It includes aspects related to surgical techniques, expansion of the donor pool, extracorporeal perfusion machines, preservation of solid organs, and donor-recipient allocation tools through artificial intelligence methods and deep-learning algorithms.

Our main objective is to be at the forefront of organ transplantation research, especially in its most innovative areas, such as increasing the number of donors, optimizing organs and assigning donors.

Our strategy is to define concrete and innovative areas where to assign competing projects, as well as participate in the main national and international scientific societies related to our area of ​​knowledge.

Our greatest achievements have been obtaining donor-recipient allocation models in liver transplantation using artificial neural networks, development of organ preservation strategies with perfusion machines and new preservation solutions, and development of avant-garde surgical techniques such as the introduction of minimally invasive surgery in organ transplantation.

Our group is related to other research groups such as the UCO Department of Computer and Numerical Analysis, the International Society for Laparoscopic Liver Surgery (ILLS), the European Association for Endoscopic Surgery EAES and the liver surgery researches groups of Hospital King´s College London (Prof. Nigel Heaton), Paul Brousse Hospital in Paris (Dr. Daniel Cherqui) and Ageo Central General Hospital Tokyo (Prof. Wakabayashi).

We work closely with several other groups in the IMIBIC such as the cardiovascular surgery group, anesthesiology group, the peritoneal carcinomatosis surgery group and group GC02 Oxidative and Nitrosative stress in acute and chronic liver disease (Dr. Manuel de la Mata).

Research Lines

In recent years, liver transplantation (LT) has overcome multiple barriers, including the resolution of several challenges in surgical technique, improvement of immunosuppressive drug strategies and prevention of long-term complications. However, the Achilles´ heel of LT remains the shortage of donors and the resulting imbalance between the number of donors and the potential candidates of a transplant. Along with the shortage of organ donors, there has been a notable concern about the assignment of the suitable donor to the most appropriate candidate on the waitlist (WL). This has come to be conventionally named donor-recipient matching (D-R). Policies in donor allocation have tried to maximize organ utilization whilst still protecting individual recipient interests. Unfortunately, the ideal D-R matching system still remains a chimera mainly due to two factors: inconsistent evidence and a lack of reliable end points. The objective of our research in this area is to explore the usefulness of various classifiers based on Artificial Intelligence (AI) to improve D-R matching. Classifiers based on Artificial Intelligence (AI) can be useful to solve decision problems related to the inclusion or removal of possible liver transplant candidates, as well as assisting in the heterogeneous field of Donor-Recipient (D-R) matching. Instead of scores inspired in biostatistics, AI models can show a great advantage by being able to handle a multitude of variables, be objective and help in cases of similar probabilities. In the field of liver transplantation, the most commonly used classifiers have been Artificial Neural Networks (ANNs) and Random Forest (RF) classifiers. ANNs are excellent tools for finding patterns that are far too complex for a clinician and are capable of generating near-perfect predictions on the data on which they are fit, yielding excellent prediction capabilities reaching 95% for 3 months graft survival. On the other hand, RF can overcome ANNs in some of their limitations, mainly due to the lack of information on the variables they provide. RF algorithms may allow for improved confidence with the use of marginal organs and better outcome after transplantation. ANNs and RF can handle a multitude of structured and unstructured parameters, and establish non-explicit relationships among risk factors of clinical relevance.

It has been an ongoing and fascinating dream for more than 100 years to keep organs alive outside of the human body. However, only relatively small steps have been made to achieve this prestigious goal, despite numerous technical advances in the field of organ perfusion, including sophisticated pump heads, shielded tubes, filter developments, blood-based perfusates, new oxygen carriers or computerized fully automatic circuit controls. Of note, while the process of organ donation, cold storage and transport appear completely reversible in healthy livers upon implantation in-vivo, with full function for many years, explanted organs, even of “good quality”, experience severe injury during only a few hours or days of cold storage or ex-situ perfusion. The reason behind remains the poorly understood metabolic needs that determine pathways of injury or repair after cold or warm ischemia. Even more challenging is the task, therefore, to improve or repair injured organs ex-situ, a claim, which has however been frequently used by several investigators, in face of an ongoing organ shortage.

In this line we investigate options and limitations of ex-situ repair of marginal livers by different perfusion techniques. We summarize the current understanding of the underlying mechanisms of different perfusion approaches. We also highlight recent achievements through clinical trials we to assess the potential design of upcoming trials based on clinical needs.

Liver steatosis has been identified to be one of the most important risk factors for primary dysfunction of a liver graft. Discarding organs is troublesome in light of the growing organ shortage; thus, each and every potential for increasing the donor pool will be illuminated in this overview. Improving fatty livers by pretreatment could significantly increase the donor pool as obesity and fatty liver disease are both dramatically rising. IRI based on ischemia with subsequent reperfusion occurs in all transplanted organs in a more or less severe way. Tissue injury by cold ischemia and subsequent warm reperfusion is a complex process. It is a combination of the injuries triggered by hypoxia and subsequent reoxygenation as well as by hypothermia and subsequent rewarming. In the beginning, organ injury by cold storage is an intracellular process. While some cells directly undergo apoptosis or necrosis even before reperfusion of the graft, complex IRI is triggered during the transplantation, which contributes to varying degrees to further damage of the graft. At least some key factors that trigger this injury have been identified, and the majority of insights have been obtained from cellular models. However, reasons for graft failure are very complex and involve donor factors and organ retrieval, organ preservation with cold and warm ischemic times, and the transplantation per se, encompassing the immune status of the recipient and surgical expertise of the transplant surgeon as well as possible surgical complications.

The anatomical description of the arterial supply of the extrahepatic bile ducts has been controversial. While some groups advocated for a terminal vascularization, others proposed the presence of a rich arterial network around the duct arteries in the middle portion of the common bile duct is sparse; in addition, this portion receives a low proportion of arterial supply compared with other areas, resulting in comparatively poor blood supply. Basically, it is formed by a longitudinal chain pattern with long, very narrow marginal arteries, making this part of the duct system vulnerable to ischemia. Some risk factors have been reported to be associated with the development of both anastomotic leaks and strictures after liver transplantation (LT). Inadequate surgical technique, arterial complications or local ischemia of the donor bile duct, the type of biliary reconstruction, and the type of liver graft (partial vs whole LT) are the major ones. Donor factors, as well as the use of external or internal drainage, are still under debate. The concept of extended criteria liver grafts is widely accepted by transplant teams. Their mechanisms of ischemia‐reperfusion injury and histological changes have been properly studied and there is increasing knowledge about how to deal with the complications associated with them. However, the concept of an “extended criteria bile duct” is still unproven and has not been reported. There are several devices used in the field of LT that help us decide if a vascular anastomosis is working well (flow‐meter, for example). However, no one has been specifically used for the real-time testing of the proper microvascularization of the bile duct. The main aim of our study was to test “in situ” the oxygenation status in different areas of the bile duct during LT using micro‐oximeters already tested in other fields of surgery and oncology. As secondary aims, we tried to identify if ducts with impaired microvascularization could be defined with a new concept of “marginal bile ducts”; and finally, we also tried to correlate these findings with histological findings, potential variables of extended criteria donors, and the development of posttransplant biliary complications.

Networks

    CIBER on Liver and Digestive Diseases (CIBERehd)

Keywords

  • liver transplant
  • pancreas transplant
  • kidney transplant
  • lung transplant
  • heart transplant
  • living donor transplantation
  • pediatric transplantation
  • split transplantation
  • expanded criteria donors
  • Donor-Recipient Matching
  • Perfusion Machines
  • Artificial Intelligence in organ transplantation

GC18 Translational Research in Surgery of Solid Organ Transplantation

Principal Investigator
Francisco Javier Briceño Delgado

Researchers
Rubén Ciria Bru
Jesús Jiménez GómezGómez
Manuel Leva VallejoVallejo
Pedro López Cillero
Ana Cristina Padial Aguado
Juan Carlos Pozo Laderas
Juan Carlos Regueiro Lopez
Juan Carlos Robles Ariza
Sebastián Rufian Peña
Juan Manuel Sánchez Hidalgo
Álvaro Arjona Sánchez
Maria Pleguezuelo Navarro

Pre-Doctoral Researchers
Irene Gómez Gómez
Elena Navarro Rodríguez

Projects

Active in 2019

Regional

Briceño Delgado, FJ. External validation of donor-recipient pairing model in liver transplants based on artificial neural networks. Funding Agency: Andalusian Progress and Health Foundation (FPS). Reference: PI-0312-2014.

Arjona Sánchez, Á. Estudio multicéntrico, randomizado, para evaluar el efecto adyuvante de la quimioterapia intraoperatoria intraperitoneal en hipertermia (HIPEC) con Mitomicina C asociada a cirugía frente a cirugía sola en el carcinoma colorrectal localmente; Funding Agency: FIBICO. Reference: PI-0424-2018-FIB.     

National

Ciria Bru, R. Rescue paragraph liver transplant grafts discarded normothermic extracorporeal perfusion. Funding Agency: Fundación Mutua Madrileña. Reference: FMM-14-002

Briceño Delgado, FJ. External validation of a donor-recipient matching model in liver transplantation based on artificial neural networks. Funding Agency: National Institute of Health Carlos III (ISCIII). Reference: PI15/01570.

International

Arjona Sánchez, A. EuroPMP - European Network on Pseudomyxoma Peritonei (Cost Action). Funding Agency: European Commission. Reference: OC-2017-1-17101.

Finished projects

Muñoz Casares, FC. Efficacy and safety of early postoperative intraperitoneal chemotherapy with paclitaxel in radical surgical treatment of ovarian peritoneal carcinomatosis. Funding agency: Regional Ministry of Equality, Health and Social Policies (CISPS). Reference: PI-0327-2013.

Briceño Delgado, FJ. External validation of donor-recipient pairing model in liver transplants based on artificial neural networks. Funding Agency: Andalusian Progress and Health Foundation (FPS). Reference: PI-0312-2014. 

Ciria Bru, R. Condition mechanisms discarded teatotic liver grafts after cold storage by normo or subnormo thermic machine perfusion. Funding Agency: National Institute of Health Carlos III (ISCIII). Reference: PI14/01559.        

Publications

Publications 2019

Arjona-Sanchez A, Rodriguez-Ortiz L, Baratti D, Schneider MA, Gutierrez-Calvo A, Garcia-Fadrique A, Tuynman JB, Cascales-Campos PA, Martin VC, Morales R, Salti GI, Arteaga X, Pacheco D, Alonso-Gomez J, Yalkin O, Villarejo-Campos P, Sanchez-Hidalgo JM, Cas. RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score. ANNALS OF SURGICAL ONCOLOGY. 2019 Aug;26(8):2595-2604. doi: 10.1245/s10434-019-07378-9.
IF: 3,857
D: 1 

Duran M, Naranjo A, Briceno J. Sigmoid Gallstone Ileus. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY. 2019 Dec;17(13):e153. doi: 10.1016/j.cgh.2019.01.031. 
IF: 7,958
Q: 1 D: 1

Ciria R, Ayllon MD, Briceno J. Difficulty scores in laparoscopic liver surgery-getting closer to a powerful and necessary tool. HEPATOBILIARY SURGERY AND NUTRITION. 2019 Aug;8(4):428-430. doi: 10.21037/hbsn.2019.02.11.
IF: 3,911
Q: 1

Ciria R, Gomez-Luque I, Ocana S, Cipriani F, Halls M, Briceno J, Okuda Y, Troisi R, Rotellar F, Soubrane O, Abu Hilal M. A Systematic Review and Meta-Analysis Comparing the Short- and Long-Term Outcomes for Laparoscopic and Open Liver Resections for Hepatocellular Carcinoma: Updated Results from the European Guidelines Meeting on Laparoscopic Liver Surgery, Southampton, UK. ANNALS OF SURGICAL ONCOLOGY. 2019 Jan;26(1):252-263. doi: 10.1245/s10434-018-6926-3. 
IF: 3,681
Q: 1

Arjona-Sanchez A, Rodriguez-Ortiz L. ASO Author Reflections: Tending Towards a Personalized Medicine for Colorectal Carcinomatosis by Adding the RAS Mutation Status in the Workup for CRS and HIPEC. ANNALS OF SURGICAL ONCOLOGY. 2019 Aug;26(8):2605-2606. doi: 10.1245/s10434-019-07362-3
IF: 3,681
Q: 1

Arjona-Sanchez A, Esquivel J, Glehen O, Passot G, Turaga KK, Labow D, Rufian-Pena S, Morales R, van der Speeten K. A minimally invasive approach for peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (HIPEC) in limited peritoneal carcinomatosis: The American Society of Peritoneal Surface Malignancies (ASPSM) multi-institution analysis. SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES. 2019 Mar;33(3):854-860. doi: 10.1007/s00464-018-6352-4. 
IF: 3,209 
Q: 1

Sanchez-Hidalgo JM, Rodriguez-Ortiz L, Arjona-Sanchez A, Rufian-Pena S, Casado-Adam A, Cosano-Alvarez A, Briceno-Delgado J. Colorectal peritoneal metastases: Optimal management review. WORLD JOURNAL OF GASTROENTEROLOGY. 2019 Jul 21;25(27):3484-3502. doi: 10.3748/wjg.v25.i27.3484.
IF: 3,411
Q: 2

Valverde A, Ciria R, Caballero-Villarraso J, Aguilar-Melero P, Ferrin G, Ranchal I, Linares C, Herencia C, Gonzalez-Rubio S, de la Mata M, Naranjo A, Briceno J. Bevacizumab Allows Preservation of Liver Function and its Regenerative Capacity after Major Hepatectomy. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY. 2019;19(11):1388-1398. doi: 10.2174/1871520619666190417162409.
IF: 2,18
Q: 3

Pozo-Laderas JC, Rodriguez-Peralvarez M, Munoz-Villanueva MC, Rivera-Espinar F, Durban-Garcia I, Munoz-Trujillo J, Robles-Arista JC, Briceno-Delgado J. Pretransplant predictors of early mortality in adult recipients of liver transplantation in the MELD-Na Era. MEDICINA INTENSIVA. 2019 Jun - Jul;43(5):261-269. doi: 10.1016/j.medin.2018.03.008.
IF: 1,982
Q: 3

Duran M, Calleja R, Naranjo A, Briceno J. Gastric and intestinal pneumatosis. GASTROENTEROLOGIA Y HEPATOLOGIA. 2019 Aug - Sep;42(7):447-448. doi: 10.1016/j.gastrohep.2019.03.004.
IF: 1,078.
Q: 4

Briceno J, Ciria R, Lopez P, Luque A, Arjona-Sanchez A, Sanchez-Hidalgo JM, Ayllon MD, Gomez-Luque I, Gomez J. Laparoscopic Living Donor Hepatectomy for Pediatric Liver Transplantation: the First 7 Cases in Spain. TRANSPLANTATION PROCEEDINGS. 2019 Jan - Feb;51(1):56-57. doi: 10.1016/j.transproceed.2018.03.140.
IF: 0,959: 
Q: 4

Briceno J, Ciria R, Gomez-Luque I. Planning Generational Change in a Liver Transplant Team. TRANSPLANTATION PROCEEDINGS. 2019 Jan - Feb;51(1):71-73. doi: 10.1016/j.transproceed.2018.04.091. 
IF: 0,959
Q: 4

Ciria R, Ayllon-Teran MD, Gonzalez-Rubio S, Gomez-Luque I, Ferrin G, Moreno A, Sanchez-Frias M, Alconchel F, Herrera C, Martin V, Sanchez-Hidalgo JM, Arjona-Sanchez A, Okuda Y, Cabrera I, Benavente B, Rodriguez MJ, Jurado-Martinez I, Duenas-Jurado JM, Rob. Rescue of Discarded Grafts for Liver Transplantation by Ex Vivo Subnormothermic and Normothermic Oxygenated Machine Perfusion: First Experience in Spain. TRANSPLANTATION PROCEEDINGS. 2019 Jan - Feb;51(1):20-24. doi: 10.1016/j.transproceed.2018.04.092.
IF: 0,959
Q: 4

Main Publications 2017

Medina-Fernandez FJ, Diaz-Lopez C, Briceno J.A Different Approach to the Use of C-Reactive Protein and Procalcitonin in Postoperative Infectious Complications. ANNALS OF SURGERY. 2017.266(6):E98-E99.
IF: 8,98
Q: 1  D: 1

Perez-Ortiz M, Gutierrez PA, Ayllon-Teran MD, Heaton N, Ciria R, Briceno J*, Hervas-Martinez C*. Synthetic semi-supervised learning in imbalanced domains: Constructing a model for donor-recipient matching in liver transplantation. KNOWLEDGE-BASED SYSTEMS. 2017.123():75-87.
IF: 4,529
Q: 1 

Arjona-Sanchez A, Rufian-Pena S. Progress in the management of primary and recurrent ovarian carcinomatosis with peritonectomy procedure and HIPEC in a high volume centre. INTERNATIONAL JOURNAL OF HYPERTHERMIA. 2017.33(5):554-561.
IF: 3,262
Q: 1 

Medina-Fernandez FJ, Escribano BM, Aguera E, Aguilar-Luque M, Feijoo M, Luque E, Garcia-Maceira FI, Pascual-Leone A, Drucker-Colin R, Tunez I. Effects of transcranial magnetic stimulation on oxidative stress in experimental autoimmune encephalomyelitis. FREE RADICAL RESEARCH. 2017.51(5):460-469.
IF: 3,188
Q: 2 

Rello J, Bello I, de Vicente R, Anchuelo AH, Ballesteros MA, Iranzo R, Rellan L, Riera J, Robles JC, EMPRET Study Investigators. Risk Factors for Mortality in 272 Patients With Lung Transplant: A Multicenter Analysis of 7 Intensive Care Units. ARCHIVOS DE BRONCONEUMOLOGIA. 2017.53(8):421-426.
IF: 2,979
Q: 2 

Medina-Fernandez FJ, Luque E, Aguilar-Luque M, Aguera E, Feijoo M, Garcia-Maceira FI, Escribano BM, Pascual-Leone A, Drucker-Colin R, Tunez I. Transcranial magnetic stimulation modifies astrocytosis, cell density and lipopolysaccharide levels in experimental, autoimmune encephalomyelitis. LIFE SCIENCES. 2017.169():20-26.
IF: 2,936
Q: 2 

Fernandez FJM, Escribano BM, Tunez I.COMMENTARY Transcranial Magnetic Stimulation in Multiple Sclerosis: A Method to Improve Movement.CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS.2017.16(3):218-219.
IF:2,506
Q:3 

Dorado-Moreno M, Perez-Ortiz M, Gutierrez PA, Ciria R, Briceno J, Hervas-Martinez C. Dynamically weighted evolutionary ordinal neural network for solving an imbalanced liver transplantation problem. ARTIFICIAL INTELLIGENCE IN MEDICINE. 2017.77():1-11.
IF: 2,009
Q: 2 

Medina-Fernandez FJ, Rodriguez-Ortiz L, Garcilazo-Arismendi DJ, Navarro-Rodriguez E, Torres-Tordera EM, Diaz-Lopez CA, Briceno J. Impact of barium enema on acute diverticulitis recurrence: A retrospective cohort study of 349 patients. JOURNAL OF DIGESTIVE DISEASES. 2017.18(7):379-387.
IF: 1,632
Q: 4 

Other Publications 2017

Martinez ML, Ferrer R, Torrents E, Gtiillamat-Prats R, Goma G, Suarez D, Alvarez-Rocha L, Laderas JCP, Martin-Loeches I, Levy MM, Artigas A. Edusepsis Study GrpImpact of Source Control in Patients With Severe Sepsis and Septic Shock. CRITICAL CARE MEDICINE. 2017.45(1):11-19.
IF: 7,05
Q: 1 

Temkin E, Torre-Cisneros J, Beovic B, Benito N, Giannella M, Gilarranz R, Jeremiah C, Loeches B, Machuca I, Jimenez-Martin MJ, Martinez JA, Mora-Rillo M, Navas E, Osthoff M, Pozo JC, Ramos JCR, Rodriguez M, Sanchez-Garcia M, Viale P, Wolff M, Carmeli Y. Ceftazidime-Avibactam as Salvage Therapy for Infections Caused by Carbapenem-Resistant Organisms. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2017.61(2):-e01964-16.
IF: 4,302
Q: 1 

Suberviola B, Rellan L, Riera J, Iranzo R, Campos AG, Robles JC, Vicente R, Minambres E, Santibanez M. Role of biomarkers in early infectious complications after lung transplantation. PLOS ONE. 2017.12(7):-e0180202.
IF: 2,806
Q: 1 

2015 European Society of Coloproctology collaborating group (Pinkney T, Battersby N, Bhangu A, et all). The Relationship between method of anastomosis and anastomotic failure after right hemicolectomy and ileo-caecal resection: an international snapshot audit. COLORECTAL DISEASE. 2017.19(8):O296-O311.
IF: 2,689
Q: 2 

Di Stasi LL, Diaz-Piedra C, Ruiz-Rabelo JF, Rieiro H, Carrion JMS, Catena A. Quantifying the cognitive cost of laparo-endoscopic single-site surgeries: Gaze-based indices. APPLIED ERGONOMICS. 2017.65():168-174.
IF: 1,866
Q: 2 

Escribano BM, Medina-Fernandez FJ, Aguilar-Luque M, Aguera E, Feijoo M, Garcia-Maceira FI, Lillo R, Vieyra-Reyes P, Giraldo AI, Luque E, Drucker-Colin R, Tunez I. Lipopolysaccharide Binding Protein and Oxidative Stress in a Multiple Sclerosis Model. NEUROTHERAPEUTICS. 2017.14(1):199-211.
IF: 5,166
Q: 1 

Perez P, Rodriguez-Peralvarez M, Guerrero L, Gonzalez V, Sanchez R, Centeno M, Poyato A, Briceno J, Sanchez-Frias M, Montero JL, De la Mata M. Incidental hepatocellular carcinoma after liver transplantation: Prevalence, histopathological features and prognostic impact. PLOS ONE. 2017.12(4):-e0175010.
IF: 2,806
Q:1 

Clinical Research

Active in 2017

Multicenter randomized clinical trial to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C associated with surgery in the treatment of locally advanced colorectal carcinoma.
PI: Dr Arjona Sánchez, Álvaro

Members

Dr. Francisco Javier Briceño Delgado

Principal Investigator

franciscoj.briceno.sspa@juntadeandalucia.es

Team

Francisco Javier Briceño Delgado Rubén Ciria Bru Jesús Jiménez GómezGómez Manuel Leva VallejoVallejo Pedro López Cillero Ana Cristina Padial Aguado Juan Carlos Pozo Laderas Juan Carlos Regueiro Lopez Juan Carlos Robles Ariza Sebastián Rufian Peña Juan Manuel Sánchez Hidalgo Álvaro Arjona Sánchez Maria Pleguezuelo Navarro Irene Gómez Gómez Elena Navarro Rodríguez