Zozaya-Larequi, G. (Gabriel)
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- NLRP3 inflammasome: a possible link between obesity-associated low-grade chronic inflammation and colorectal cancer development(NCBI, 2018) Unamuno, X. (Xabier); Marti, P. (Pablo); Baixauli-Fons, J. (Jorge); Catalan, V. (Victoria); Ahechu-Garayoa, P. (Patricia); Zozaya-Larequi, G. (Gabriel); Frühbeck, G. (Gema); Hernandez-Lizoain, J.L. (Jose Luis)Emerging evidence reveals that adipose tissue-associated inflammation is a main mechanism whereby obesity promotes colorectal cancer risk and progression. Increased inflammasome activity in adipose tissue has been proposed as an important mediator of obesity-induced inflammation and insulin resistance development. Chronic inflammation in tumor microenvironments has a great impact on tumor development and immunity, representing a key factor in the response to therapy. In this context, the inflammasomes, main components of the innate immune system, play an important role in cancer development showing tumor promoting or tumor suppressive actions depending on the type of tumor, the specific inflammasome involved, and the downstream effector molecules. The inflammasomes are large multiprotein complexes with the capacity to regulate the activation of caspase-1. In turn, caspase-1 enhances the proteolytic cleavage and the secretion of the inflammatory cytokines interleukin (IL)-1 beta and IL-18, leading to infiltration of more immune cells and resulting in the generation and maintenance of an inflammatory microenvironment surrounding cancer cells. The inflammasomes also regulate pyroptosis, a rapid and inflammation-associated form of cell death. Recent studies indicate that the inflammasomes can be activated by fatty acids and high glucose levels linking metabolic danger signals to the activation of inflammation and cancer development. These data suggest that activation of the inflammasomes may represent a crucial step in the obesity-associated cancer development. This review will also focus on the potential of inflammasome-activated pathways to develop new therapeutic strategies for the prevention and treatment of obesity-associated colorectal cancer development.
- Cirugía laparoscópica hepática y pancreática(Gobierno de Navarra. Departamento de Salud, 2005) Valenti, V. (Víctor); Pastor, C. (Carlos); Rotellar, F. (Fernando); Poveda, I. (Ignacio); Pardo, F. (Fernando); Zozaya-Larequi, G. (Gabriel); Marti-Cruchaga, P. (Pablo)The development of laparoscopic surgery also includes the more complex procedures of abdominal surgery such as those that affect the liver and the pancreas. From diagnostic laparoscopy, accompanied by laparoscopic echography, to major hepatic or pancreatic resections, the laparoscopic approach has spread and today encompasses practically all of the surgical procedures in hepatopancreatic pathology. Without forgetting that the aim of minimally invasive surgery is not a better aesthetic result but the reduction of postoperative complications, it is undeniable that the laparoscopic approach has brought great benefits for the patient in every type of surgery except, for the time being, in the case of big resections such as left or right hepatectomy or resections of segments VII and VIII. Pancreatic surgery has undergone a great development with laparoscopy, especially in the field of distal pancreatectomy due to cystic and neuroendocrine tumours where the approach of choice is laparoscopic. Laparoscopy similarly plays an important role, together with echolaparoscopy, in staging pancreatic tumours, prior to open surgery or for indicating suitable treatment. In coming years, it is to be hoped that it will continue to undergo an exponential development and, together with the advances in robotics, it will be possible to witness a greater impact of the laparoscopic approach on the field of hepatic and pancreatic surgery.
- Cirugía laparoscópica biliar(Gobierno de Navarra. Departamento de Salud, 2005) Valenti, V. (Víctor); Pastor, C. (Carlos); Rotellar, F. (Fernando); Poveda, I. (Ignacio); Zozaya-Larequi, G. (Gabriel); Marti-Cruchaga, P. (Pablo)The following article briefly sets out the possible new protocols that can be applied in biliary pathology, arising from the changes brought about by the appearance of new techniques of laparoscopic biliary surgery. It offers a synthesis of the latest and most novel articles on surgical technique and management in different biliary pathologies such as Choledocholithiasis and cholecystitis. It can be concluded that management will differ greatly, depending on the technical capacities of the centre that is called upon to deal with one of these pathologies. A standard protocol for everybody cannot thus be established at present. Teh differences between endoscopic retrograde cholangiopancreatography and intraoperative laparoscopic cholangiography have still to be demonstrated, it is not possible to make generalisations about whether one technique is more useful than the other. The same could be said about whether access to the main biliary path should be achieved through the cystic conduct or whether, on the contrary, a choledochotomy should be performed.
- Minimally invasive liver surgery for hepatocellular carcinoma in patients with portal hypertension(Oxford University Press, 2023) Rotellar, F. (Fernando); Almeida, A. (Ana); Luján-Colás, J. (Juan); Zozaya-Larequi, G. (Gabriel); Sangro, B. (Bruno); Blanco, N. (Nuria); Sabatella, L. (Lucas); Marti-Cruchaga, P. (Pablo); Aliseda, D. (Daniel)For patients with early stage hepatocellular carcinoma (HCC), liver resection is a mainstay of curative treatment. Patients with a solitary tumour, Child–Pugh A cirrhosis and serum bilirubin of 1 mg/dl are considered ideal candidates for liver resection1,2 . For patients with portal hypertension, current guidelines recommend careful consideration of liver resection based on the hierarchical interaction of portal hypertension, liver function and resection extent1,3 . Open liver resection has been used in the majority of published studies on liver resection and portal hypertension. Although there is limited published experience of minimally invasive liver resection (MILR), using MILR in these patients appears to be associated with favourable outcomes4 . Particularly in patients with Child–Pugh A cirrhosis, but also in patients with more advanced cirrhosis5 , MILR offers significant advantages in the surgical treatment of HCC including reduced intraoperative bleeding, fewer complications and minimized surgical aggression, which improves recovery6,7 . If these benefits are also found in patients with portal hypertension, MILR may represent a step forward in the surgical treatment of patients with HCC and portal hypertension. This systematic review and meta-analysis aimed to summarize the intraoperative, postoperative and survival outcomes of MILR in patients with HCC and portal hypertension.
- Liver resection and transplantation following Yttrium-90 radioembolization for primary malignant liver tumors: a 15-year single-center experience(2023) Rotellar, F. (Fernando); Pardo-Sanchez, F. (Fernando); Ortega-Montes, A. (Ana); Lopez-Olaondo, L. (Luis); Benito-Boíllos, A. (Alberto); Zozaya-Larequi, G. (Gabriel); Hidalgo, F. (Francisco); Martinez-de-la-Cuesta, A. (Antonio); Sangro, B. (Bruno); Ponz-Sarvise, M. (Mariano); Iñarrairaegui, M. (Mercedes); Bilbao, J.I. (José I.); Herrero, J.I. (José Ignacio); Marti-Cruchaga, P. (Pablo); Rodriguez-Fraile, M. (Macarena); Rodríguez-Rodríguez, J. (Javier); Aliseda, D. (Daniel)Simple Summary Radioembolization is a locoregional therapy used in primary liver malignancies with different applications depending on the treatment goal. The aim of this retrospective study was to evaluate postoperative and long-term survival outcomes of patients with unresectable or high biological risk HCC and ICC treated with RE that were finally rescued to liver surgery with curative intent. In a cohort of 34 patients, we assessed that liver resection and transplantation after RE seem safe and feasible with adequate short-term outcomes. Moreover, long-term outcomes after RE and LR were optimal, with a 10-year OS rate greater than 50% for HCC and ICC patients. On the other hand, the 10-year OS rates from RE were also greater than 50% for patients with HCC downstaged or bridged to LT. Radioembolization (RE) may help local control and achieve tumor reduction while hypertrophies healthy liver and provides a test of time. For liver transplant (LT) candidates, it may attain downstaging for initially non-candidates and bridging during the waitlist. Methods: Patients diagnosed with HCC and ICC treated by RE with further liver resection (LR) or LT between 2005-2020 were included. All patients selected were discarded for the upfront surgical approach for not accomplishing oncological or surgical safety criteria after a multidisciplinary team assessment. Data for clinicopathological details, postoperative, and survival outcomes were retrospectively reviewed from a prospectively maintained database. Results: A total of 34 patients underwent surgery following RE (21 LR and 13 LT). Clavien-Dindo grade III-IV complications and mortality rates were 19.0% and 9.5% for LR and 7.7% and 0% for LT, respectively. After RE, for HCC and ICC patients in the LR group, 10-year OS rates were 57% and 60%, and 10-year DFS rates were 43.1% and 60%, respectively. For HCC patients in the LT group, 10-year OS and DFS rates from RE were 51.3% and 43.3%, respectively. Conclusion: Liver resection after RE is safe and feasible with optimal short-term outcomes. Patients diagnosed with unresectable or high biological risk HCC or ICC, treated with RE, and rescued by LR may achieve optimal global and DFS rates. On the other hand, bridging or downstaging strategies to LT with RE in HCC patients show adequate recurrence rates as well as long-term survival.
- Association of laparoscopic surgery with improved perioperative and survival outcomes in patients with resectable intrahepatic cholangiocarcinoma: A systematic seview and meta-analysis from propensity-score matched studies(Springer, 2023) Goh, B.K.P. (Brian K. P.); Rotellar, F. (Fernando); Zozaya-Larequi, G. (Gabriel); Blanco, N. (Nuria); Marti-Cruchaga, P. (Pablo); Sapisochin, G. (Gonzalo); Aliseda, D. (Daniel)Background: Recent studies have associated laparoscopic surgery with better overall survival (OS) in patients with hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). The potential benefits of laparoscopic liver resection (LLR) over open liver resection (OLR) have not been demonstrated in patients with intrahepatic cholangiocarcinoma (iCC). Methods: A systematic review of the PubMed, EMBASE, and Web of Science databases was performed to search studies comparing OS and perioperative outcome for patients with resectable iCC. Propensity-score matched (PSM) studies published from database inception to May 1, 2022 were eligible. A frequentist, patient-level, one-stage meta-analysis was performed to analyze the differences in OS between LLR and OLR. Second, intraoperative, postoperative, and oncological outcomes were compared between the two approaches by using a random-effects DerSimonian-Laird model. Results: Six PSM studies involving data from 1.042 patients (530 OLR vs. 512 LLR) were included. LLR in patients with resectable iCC was found to significantly decrease the hazard of death (stratified hazard ratio [HR]: 0.795 [95% confidence interval [CI]: 0.638-0.992]) compared with OLR. Moreover, LLR appears to be significantly associated with a decrease in intraoperative bleeding (- 161.47 ml [95% CI - 237.26 to - 85.69 ml]) and transfusion (OR = 0.41 [95% CI 0.26-0.69]), as well as with a shorter hospital stay (- 3.16 days [95% CI - 4.98 to - 1.34]) and a lower rate of major (Clavien-Dindo ≥III) complications (OR = 0.60 [95% CI 0.39-0.93]). Conclusions: This large meta-analysis of PSM studies shows that LLR in patients with resectable iCC is associated with improved perioperative outcomes and, being conservative, yields similar OS outcomes compared with OLR.
- Análisis de la morbilidad postoperatoria en pacientes con adenocarcinoma gástrico tratados según protocolo de quimiorradioterapia preoperatoria y cirugía(Elsevier, 2009-12) Valenti, V. (Víctor); Blasco-Blanco, M. (Manuel); Bueno, A. (Álvaro); Martinez-Regueira, F. (Fernando); Álvarez-Cienfuegos, J. (Javier); Zozaya-Larequi, G. (Gabriel); Hernandez-Lizoain, J.L. (Jose Luis); Gil, A. (Aurora); Marti-Cruchaga, P. (Pablo); Pedano, N. (Nicolás); Beorlegui, C. (Carmen)Introducción El impacto del tratamiento neoadyuvante sobre las complicaciones postoperatorias en el cáncer de estómago es motivo de controversia. El objetivo de este trabajo es analizar la morbilidad y la mortalidad postoperatoria en un grupo de pacientes a los que se les había aplicado un protocolo de quimiorradioterapia preoperatoria, así como identificar posibles factores de riesgo que se asocian al desarrollo de complicaciones. Material y métodos Entre junio de 2005 y junio de 2008, pacientes diagnosticados de adenocarcinoma gástrico localmente avanzado se intervinieron en nuestro Centro tras haber seguido un protocolo de quimiorradioterapia preoperatoria. Se recogieron prospectivamente los datos sobre morbilidad y mortalidad postoperatoria y se analizaron las variables dependientes relacionadas con los pacientes, con el tipo de intervención y las características tumorales. Resultados Se evaluaron 40 pacientes. La morbilidad y la mortalidad global fue del 32,5% (13 pacientes) y del 2,5% (un paciente), respectivamente. Las complicaciones más frecuentes fueron la neumonía en el 12,9% y la sepsis por catéter en el 9,7% de los pacientes. Los factores de riesgo para el desarrollo de complicaciones fueron el índice de masa corporal (>25 kg/m2) y la inclusión en la resección del páncreas o del bazo. Conclusiones El tratamiento preoperatorio con quimiorradioterapia en pacientes con cáncer de estómago localmente avanzado no incrementa la incidencia de complicaciones postoperatorias. La condición preoperatoria del paciente (índice de masa corporal) y la extensión de la cirugía del bazo y del páncreas son factores pronósticos de complicaciones postoperatorias precoces. Abstract Introduction The impact of neoadjuvant treatment on the postoperative complications in stomach cancer is a subject of controversy. The aim of this study is to analyse the post-surgical morbidity and mortality in a group of patients who were treated using a chemoradiotherapy protocol before surgery, as well as to identify the possible risk factors that may be associated with the development of complications. Material and methods Patients diagnosed with locally advanced gastric adenocarcinoma between June 2005 and June 2008 were operated on in our Centre after having followed a preoperative chemoradiotherapy protocol. Data on postoperative morbidity and mortality were collected retrospectively and the dependent variables associated with the patients, the type of intervention and the tumour characteristics were analysed. Results A total of 40 patients were evaluated. The overall morbidity and mortality was 32.5% (13 patients) and 2.5% (1 patient), respectively. The most frequent complications were pneumonia in 12.9% and sepsis due to the catheter in 9.7% of the patients. The risk factors for the development of complications were the body mass index (BMI 25 kg/m2) and the inclusion of the pancreas and/or spleen in the resection. Conclusions Preoperative treatment with chemoradiotherapy in patients with locally advanced stomach cancer does not increase the incidence of post-surgical complication. The preoperative condition of the patient (BMI) and extending the surgery to the spleen and pancreas are prognostic factors of early postoperative complications.
- Therapeutic drug monitoring of neoadjuvant mFOLFIRINOX in resected pancreatic ductal adenocarcinoma(Elsevier, 2023) Chopitea, A. (Ana); Rotellar, F. (Fernando); Aldaz, A. (Azucena); Urrizola-Martínez, A. (Amaia); Arbea-Moreno, L. (Leire); Pardo, F. (Fernando); Zozaya-Larequi, G. (Gabriel); Subtil, J.C. (José Carlos); Ponz-Sarvise, M. (Mariano); Sala-Elarre, P. (Pablo); Marti-Cruchaga, P. (Pablo); Vilalta, A. (Anna); Rodríguez-Rodríguez, J. (Javier)Background: Despite a potentially curative treatment, the prognosis after upfront surgery and adjuvant chemotherapy for patients with resectable pancreatic ductal adenocarcinoma (PDAC) is poor. Modified FOLFIRINOX (mFOLFIRINOX) is a cornerstone in the systemic treatment of PDAC, including the neoadjuvant setting. Pharmacokinetic-guided (PKG) dosing has demonstrated beneficial effects in other tumors, but scarce data is available in pancreatic cancer. Methods: Forty-six patients with resected PDAC after mFOLFIRINOX neoadjuvant approach and included in an institutional protocol for anticancer drug monitoring were retrospectively analyzed. 5-Fluorouracil (5-FU) dosage was adjusted throughout neoadjuvant treatment according to pharmacokinetic parameters and Irinotecan (CPT-11) pharmacokinetic variables were retrospectively estimated. Results: By exploratory univariate analyses, a significantly longer progression-free survival was observed for patients with either 5-FU area under the curve (AUC) above 28 mcg$h/mL or CPT-11 AUC values below 10 mcg$h/mL. In the multivariate analyses adjusted by age, gender, performance status and resectability after stratification according to both pharmacokinetic parameters, the risk of progression was significantly reduced in patients with 5-FU AUC 28 mcg$h/mL [HR ¼ 0.251, 95% CI 0.096e0.656; p ¼ 0.005] and CPT-11 AUC <10 mcg$h/mL [HR ¼ 0.189, 95% CI 0.073e0.486, p ¼ 0.001]. Conclusions: Pharmacokinetically-guided dose adjustment of standard chemotherapy treatments might improve survival outcomes in patients with pancreatic ductal adenocarcinoma.
- Anatomical left hepatectomy extended to caudate lobe due to colorectal metastasis with intrabiliary growth: securing optimal margins with a laennec’s capsule approach and vein‐guided resection(Springer, 2024) Rotellar, F. (Fernando); Zozaya-Larequi, G. (Gabriel); Lapuente, F. (Fernando); Blanco, N. (Nuria); Sabatella, L. (Lucas); Marti-Cruchaga, P. (Pablo); Aliseda, D. (Daniel)Metastases of colorectal cancer (CRLM) present in up to 15% of cases an intrabiliary growth pattern (IGP) resembling cholangiocarcinoma behavior. An appropriate diagnosis is paramount, as IGP modifes the surgical strategy.
- Full laparoscopic vascular reconstruction for portal tumoral invasion during a right hepatectomy using the caudal approach(2022) Benito-Boilos, A. (Alberto); Rotellar, F. (Fernando); Almeida, A. (Ana); Lopez-Olaondo, L. (Luis); Zozaya-Larequi, G. (Gabriel); Hidalgo, F. (Francisco); Lujan-Mompean, J.A. (Juan Antonio); Marti-Cruchaga, P. (Pablo)Background: Laparoscopic liver surgery has progressively evolved. Consequently, liver procedures are increasingly performed laparoscopically, particularly in experienced centers. However, vascular resection and reconstruction still are considered a limitation for laparoscopy1 due to the risk of bleeding and the technical difficulty. Methods: A 72-year-old woman with a history of colorectal cancer had a 10 cm metastasis diagnosed in the right hemiliver with tumoral invasion of the right portal branch and tumor thrombus advancing to the portal confluence. After adjuvant chemotherapy and with stable disease, surgical resection was planned.2,3 Tips to avoid portal stenosis were carefully followed. Results: The operation was performed with a fully laparoscopic procedure. To minimize manipulation, an in situ right hepatectomy was performed.4 The right hepatic artery was dissected and ligated. The liver transection was guided with a caudal approach of the middle hepatic vein.5 The right biliary duct was then divided, achieving an excellent exposure of the portal bifurcation. The main and left portal trunks were occluded with vascular clamps, and the right portal vein was sharply divided with scissors. The stump was sutured to minimize backflow bleeding and to cover the tumor thrombus. Then, the portal opening was transversally sutured with a 5/0 running suture. The clamps were released, and the authors observed no bleeding and an adequate caliber with no stenosis. The procedure was completed in the standard fashion. The postoperative course was uneventful, and the woman was discharged on postoperative day 3. No early or late complications were observed.6 CONCLUSIONS: In selected cases, patients who require vascular resection and reconstruction during hepatectomies can benefit from the advantages of a laparoscopic approach.