Research groups

GE09 Research in peritoneal and retroperitoneal oncological surgery

The emerging research group GE09 "Research in peritoneal and retroperitoneal oncological surgery" was born as a consequence of the care trajectory of the Oncological Surgery Unit that has been a reference for more than two decades in the treatment of peritoneal carcinomatosis and complex retroperitoneal tumors that require multivisceral and vascular resective surgeries. During this trajectory, the Unit has developed a continuous research work focused on the treatment of peritoneal carcinomatosis of ovarian origin. Recently, our group has developed new lines of research such as the prevention of carcinomatosis in advanced colon cancer or the study of pseudomyxoma peritonei within the framework of a European collaboration where we are members of its management team. The development of these lines has led to obtaining public and private grants that allow the constitution of a basic-clinical research team. The basic research of our group is coordinated by Dr. Antonio Romero, and the clinical researchers' team includes members of the Oncological Surgery Unit (5), the Coloproctology Unit (2), the Pathological Anatomy Unit (2) as well as resident medical interns (2).

The group has long-term objectives in various scenarios described in the research lines. In summary, for the peritoneal pseudomyxoma, our aim is to describe the altered molecular routes that lead to the genesis of this rare tumor and to generate possible targets for treatment, in the prevention of carcinomatosis. We aim to demonstrate the benefit of intraperitoneal chemotherapy as an assistant to the surgery in cases of advanced colon cancer. Another objective is purely clinic: the implementation of a minimally invasive approach in peritoneal carcinomatosis and the collection of the greatest international experience through the coordination by our group of an international registry.

Due to its emerging quality, our group works together and in collaboration with other established research groups such as GC18 (Translational Research in Surgery of Solid Organ Transplantation), also belonging to the HURS Surgery Unit, GC10 Hormonal Regulation of Energy Balance, Puberty and Reproduction, and GC08 Hormones and Cancer.

Research Lines

Pseudomyxoma Peritonei (PMP) is a rare malignant disease defined by the progressive multifocal accumulation of mucinous tumor tissue in the peritoneal cavity, with an incidence of 1-2 cases/million of people/year, according to the National Organization of Rare Diseases-NORD. Our Oncology Surgery Unit of the Reina Sofía University Hospital (HURS) has been named a Reference Center, thanks to having one of the most extensive experiences in our country. Advancing the knowledge of this pathology is critical to improving not only the survival rate of patients but also their quality of life. In this sense, although there is no cure of this disease, treatment of patients with complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has shown a survival benefit. Despite the surgical and therapeutic effort, recurrence is common with subsequent progression and death. However, the low incidence makes it challenging to know the molecular mechanisms which are behind the proliferation and recurrence. Besides, the treatment of recurrence after surgery and HIPEC has not yet been established, because the chemotherapy treatment doesn’t reproduce the effects in metastatic colorectal cancer, and there is no evidence on the benefits.

For all of the above, it’s urgent to find drugs for this type of tumor and specific markers capable of preventing its progression and recurrence. However, the exceptional nature of this disease makes it highly challenging to carry out clinical studies. In this context, the molecular characterization of the tumor types will allow a better prognosis and a personalized and effective choice of treatment. In this sense, the development of animal models to reproduce human PMP will be critical to developing therapeutic targets as well as to test new biomarkers for earlier diagnosis and early detection of recurrence.

Due to the exceptional nature of this disease and the need for new treatment strategies, a European working group formed by reference PMP groups has been established. Our team has been integrated into an international collaborative action within European Cooperation in Science and Technology (COST) under the name of EuroPMP (COST CA 1701), and our Unit is in the Development Committee. This COST action allows collaborative events in PMP research.

The presence of diffuse peritoneal malignancy, called peritoneal carcinomatosis, leads to a fatal prognosis in the evolution of cancer disease. Since the incorporation of complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC), the prognosis of these patients has improved becoming similar to other metastases. Improvements in survival using CRS+HIPEC in colon carcinomatosis have led to the dissemination of this treatment in most of the specialized units.

One of the key aspects in this field, is the early identification of patients under risk for peritoneal carcinomatosis and to prevent its development. This is the purpose of our research line, where we are applying adjuvant therapies to radical surgery in locally advanced colon tumors. This adjuvant therapy is the administration of HIPEC associated with conventional surgery. In this context, our team is coordinating more than 20 national reference units in a Multi-centre and randomize study called HIPECT4.

The use of minimally invasive technique has become a standard approach in the treatment of various digestive tumors and liver metastases. Our Oncological Surgery Unit of the HURS is a pioneer in the development of laparoscopy in complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (lap-CRS+HIPEC); offering previously selected patients an approach with minimal aggression to achieve total elimination of peritoneal disease together with intraperitoneal chemotherapy. This technology results in a minimum injury, reduced hospital stay and better general health, before going back to the systemic treatment. As a novel treatment, it’s critical to acquire the maximum international experience to get conclusions about the benefits of this approach and its impact on the development of the disease. In this sense, the GE09 group has developed and coordinates the international registration PSOGI (Peritoneal Surface Oncologic Group International) for lap-CRS+HIPEC.

The treatment of this peritoneal disease is a challenge from a surgical and oncological point of view. In this sense, our clinical team is one of the Reference Units in performing complete cytoreductive surgery associated with intraperitoneal chemotherapy; we have treated more than 500 cases of the advanced stage of the disease since 1997. The current goal of our group in this research line is three-fold: i) a follow-up observational study of these cases and their prognosis, ii) the use of inflammatory markers, and iii) a molecular study of the effect of cytotoxic drugs designed for use in the hyperthermia and intraperitoneal chemotherapy.

Networks

Keywords

  • peritoneal carcinomatosis
  • HIPEC
  • pseudomyxoma peritonei
  • mesothelioma
  • sarcoma

Additional Information

Ongoing Projects

Alvaro Arjona Sánchez; Antonio Romero Ruiz. Molecular characterization of Pseudomyxima Peritonei and development of new prognosis biomarkers and therapeutic targets by using a human xenograft mouse model. Funding agency: National Institute of Health Carlos III (ISCIII). Reference: PI19/01603.

Alvaro Arjona Sánchez. HIPECT4: Multi-Centre and randomize study to evaluate the adjuvant effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Mitomycin C associated to surgery versus surgery without HIPEC, in locally advanced colorectal carcinoma. Nº EudraCT: 2015-001801-15 NCT02614534. Evaluated and Accepted by Regional Ministry of Equality, Health and Social Policies (CISPS) and funded by FIBICO.  Reference: PI-0424-2018.

Antonio Romero-Ruiz. Molecular characterization of Pseudomyxima Peritonei and development of new therapeutic targets by using proteomic approaches. Funding agency: Proteored (ISCIII). Reference: ProteoRed - 0000141-2020.

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

Recent Publications (2020)

Rodríguez-Ortiz L, Arjona-Sánchez Á, Ibañez-Rubio M, Sánchez-Hidalgo J, Casado-Adam A, Rufián-Peña S, Briceño-Delgado J. Laparoscopic Cytoreductive Surgery and HIPEC: A Comparative Matched Analysis. Surg Endosc. 2020 Apr 23. PMID: 32328823. DOI: 10.1007/s00464-020-07572-x
IF: 3.2  Q: 1

Viyuela García C, Medina Fernándeza FJ, Arjona-Sánchez Á, Casado-AdamÁ, Sánchez Hidalgo JM, Rufián Peña S, Briceño Delgado J. Systemic inflammatory markers for the detection of infectious complications and safe discharge after cytoreductive surgery and HIPEC. Surgical Oncology, Volume 34, September 2020, Pages 163-167. DOI: 10.1016/j.suronc.2020.04.013
IF: 3.0 Q: 1

Arjona-Sánchez A, Cortés-Guiral D, Duran-Martínez M. Complete Laparoscopic Pelvic Peritonectomy plus Hyperthermic Intraperitoneal Chemotherapy. Tech Coloproctology. 2020 Accepted. 
IF: 2,68 Q: 2

Segura-Sampedro JJ, Morales-Soriano R, Arjona-Sánchez Á, Cascales-Campos P. Secondary surgical cytoreduction needs to be assessed taking into account surgical technique, completeness of cytoreduction, and extent of disease. World J Surg Oncol. 2020. DOI: 10.1186/s12957-020-01853-4.
IF: 1,96 Q: 2

Navarro-Barrios Á, Gil-Martínez J, Ramos-Bernardo I, Barrios P, Muñoz-Casares C, Torres-Melero J, Pereira F, Manzanedo I, Arjona Á, Martínez-Regueira F, Cascales-Campos PA. Intraperitoneal hyperthermic chemotherapy after cytoreduction in patients with peritoneal metastases from endometrial cancer. The next frontier? Surgical Oncology. Volume 33, June 2020, Pages 19-23. DOI: 10.1016/j.suronc.2019.12.002
IF: 3.0 Q: 1

GE09 Research in peritoneal and retroperitoneal oncological surgery

Principal Investigator
Álvaro Arjona Sánchez

Researchers
Antonio Romero Ruiz

Post-Doctoral Researchers
Ángela Casado Adam

Pre-Doctoral Researchers
Lidia Rodríguez Ortiz
Blanca Rufián Andújar
Francisca Valenzuela Molina

Technical and Administrative Staff
César Díaz López
Ana Martínez López
Francisco Javier Medina Fernandez
Juan Manuel Sanchez Hidalgo

Projects

Active in 2019

National

Alvaro Arjona Sánchez; Antonio Romero Ruiz. Molecular characterization of Pseudomyxima Peritonei and development of new prognosis biomarkers and therapeutic targets by using a human xenograft mouse model. Funding agency: National Institute of Health Carlos III (ISCIII). Reference: PI19/01603.

Alvaro Arjona Sánchez. HIPECT4: Multi-Centre and randomize study to evaluate the adjuvant effect of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with Mitomycin C associated to surgery versus surgery without HIPEC, in locally advanced colorectal carcinoma. Nº EudraCT: 2015-001801-15 NCT02614534. Evaluated and Accepted by Regional Ministry of Equality, Health and Social Policies (CISPS) and funded by FIBICO.  Reference: PI-0424-2018.

Cesar Díaz López. Randomized prospective non-inferiority clinical trial of treatment of rectal cáncer T2-T3sN0M0 with preoperative chemo-radioterapy and transanal endoscopic micro-surgery (TEM) versus total mesorectum excision (TME). Promoter: Dr. Xavier Serra Aracil. Servicio de Cirugía General y Servicio de Oncología, Corporació Sanitaria Parc Tauli. EudraCT: 2009-014310-94 

In collaboration:

Justo Castaño Fuentes. Alterations of alternative splicing machinery in pancreatic cancer: identification of new diagnostic, prognosis and therapeutic biomarkers. Funding agency: Spanish Ministry of Economy and Competitiveness (MINECO). Reference: BFU 2016-80360-R.

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

International:

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

Publications

Main Publications 2019

Arjona-Sanchez A, Rodriguez-Ortiz L, Baratti D, Schneider MA, Gutiérrez-Calvo A, García-Fadrique A, Tuynman JB, Cascales-Campos PA, Martín VC, Morales R, Salti GI, Arteaga X, Pacheco D, Alonso-Gomez J, Yalkin O, Villarejo-Campos P, Sanchez-Hidalgo JM, Casado-Adam A, Cosano-Alvarez A, Rufian-Peña S, Briceño J. 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. Ann Surg Oncol. 2019 Aug;26(8):2595-2604. PMID 31111351
IF: 3.857 D: 1

Sánchez-Hidalgo JM, Rodríguez-Ortiz J, Arjona-Sánchez Á, Rufián-Peña S, Casado-Adam Á, Cosano-Álvarez A, Briceño-Delgado J. Colorectal Peritoneal Metastases: Optimal Management Review. World J Gastroenterol. 2019 Jul 21;25(27):3484-3502. PMID: 31367152
IF: 3.411 Q: 2

Arjona-Sanchez A, Esquivel J, Glehen O, Passot G, Turaga KK, Labow D, Rufian-Peña 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. Surg Endosc. 2019 Mar;33(3):854-860. PMID 30003349
IF: 2.374 Q: 1

Arjona-Sanchez Á, 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. Ann Surg Oncol. 2019 Aug;26-8, pp.2605-2606. PMID: 31004296
IF: 3.681 Q: 1

Arjona-Sánchez Á, Durán M, Sánchez-Hidalgo JM, Rufian-Peña S. Peritoneal Carcinomatosis From Ovarian Carcinoma Treated by Interval Laparoscopic Complete Cytoreduction and HIPEC With Extraction Through Natural Orifice. Surg Oncol. 2019 Dec;31:14-15. PMID: 31472328
IF: 3.0 Q: 1

Romero-Ruiz A, Avendaño MS, Dominguez F, Lozoya T, Molina-Abril H, Sangiao-Alvarellos S, Gurrea M, Lara-Chica M, Fernandez-Sanchez M, Torres E, Perdices-López C, Abbara A, Steffani L, Calzado MA, Dhillo WS, Pellicer A,Tena-Sempere M. Deregulation of miR-324/Kiss1/kisspeptin in early ectopic pregnancy: Mechanistic findings with clinical and diagnostic implication. American Journal of Obstetrics and Gynecology. 2019. Vol 220 (5), pp. 480e1 - 480e17. PMID: 30707968
IF: 6.1 D: 1

Romero-Ruiz A, Skorupskaite K, Gaytan F, Torres-Jimenez E, Perdices-Lopez C, Mannaerts BM, Qi S, Leon S, Manfredi-Lozano M, Lopez-Rodriguez C, Avendaño MS, Sanchez-Garrido MA, Vazquez MJ, Pinilla L, van Duin M, Kohout T, Anderson RA, Tena-Sempere, M. Kisspeptin Treatment Induces Gonadotropic Responses and Rescues Ovulation in Preclinical Models & Women with Polycystic Ovary Syndrome. Human Reproduction. 2019 Dec 1;34(12):2495-2512. PMID: 31820802
IF: 5.5 D: 1

Other Publications 2019

Manzanedo I, Pereira F, Rihuete Caro C, Pérez-Viejo E, Serrano Á, Gutiérrez Calvo A, Regueira FM, Casado-Adam Á, Cascales-Campos PA, Arteaga X, García-Fadrique A, Gómez Sanz R, López García A, Zozaya G, Arjona Á, Gil Martínez J. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer With Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP). Ann Surg Oncol. 2019 Aug;26(8):2615-2621. PMID: 31115852
IF: 3.681 Q: 1

Velasco I, León S, Barroso A, Ruiz-Pino F, Heras V, Torres E, León M, Ruohonen ST, García-Galiano D, Romero-Ruiz A, Sánchez-Garrido MA, Olhsson C, Castellano JM, Roa J, Poutanen M, Pinilla L, Vázquez MJ, Tena-Sempere M. Gonadal Hormone-Dependent vs. -Independent Effects of Kisspeptin Signaling in the Control of Body Weight and Metabolic Homeostasis. Metabolism. Jun 18. pii: S0026-0495(19)30116-7.  2019. ISSN 0026-0495. PMID: 31226351
IF: 6.5 D:1

Members

Dr. Álvaro Arjona Sánchez

Principal Investigator

Team

Álvaro Arjona Sánchez Antonio Romero Ruiz Ángela Casado Adam Lidia Rodríguez Ortiz Blanca Rufián Andújar Francisca Valenzuela Molina César Díaz López Ana Martínez López Francisco Javier Medina Fernandez Juan Manuel Sanchez Hidalgo