Estudio de la viabilidad de los xenoinjertos de adenocarcinomas y tumores periampulares de páncreas

Debido al mal pronóstico de los tumores del área periampular y especialmente de adenocarcinoma de páncreas (ADCP), resulta fundamental la búsqueda de biomarcadores para su detección precoz y de moléculas que permitan el desarrollo urgente de nuevas estrategias terapéuticas. Para ello, los modelos animales han demostrado ser muy útiles en la evolución de los avances en el cáncer de páncreas. Han contribuido al estudio de nuevos quimioterápicos que posteriormente han sido trasladados a ensayos clínicos con humanos que han demostrado un aumento en la supervivencia. El desarrollo de los quimioterápicos y otras moléculas antitumorales se encuentra íntimamente relacionado con los modelos experimentales. Durante los últimos 50 años, los xenoinjertos subcutáneos derivados de líneas celulares cultivadas in vitro han sido ampliamente utilizados. Multitud de quimioterápicos han sido testados utilizando estos modelos. Sin embargo, fármacos que funcionan bien en el ratón no son necesariamente efectivos en el ser humano. Desde los años 70, se han utilizado muestras de cánceres humanos tomados mediante biopsia o mediante cirugía que posteriormente han sido implantados directamente en ratones. Estos xenoinjertos, también conocidos como “tumorgraft” mantienen la morfología tumoral inicial, así como las mutaciones genéticas que le acompañan. Sin embargo, estos modelos fueron inicialmente desechados debido a su alto índice de rechazos. Recientemente, se ha retomado esta línea de investigación gracias al desarrollo de nuevas cepas de ratones inmunodeprimidos modificadas genéticamente que han minimizado las tasas rechazo. De esta manera, ha sido posible que este modelo sea competitivo a la hora de analizar la eficacia de las distintas drogas para el estudio de ADCP. Siguiendo esta línea de trabajo hemos desarrollados tres modelos experimentales mediante el uso de xenoinjertos: subcutáneo, intraabdominal y pancreático. El objetivo principal de este estudio es valorar la viabilidad de los xenoinjertos ortotópicos (intrapancreático) y heterotópicos (intraabdominal y subcutáneo) de cánceres de páncreas humanos implantados en ratones desnudos

Post-transplant lymphoproliferative disease in liver transplant recipients.

Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease

Post-transplant lymphoproliferative disease in liver transplant recipients

Introduction: Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Methods: Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. Results: PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. Conclusion: PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease

Implication of the presence of a variant hepatic artery during the Whipple procedure

Introduction: The anatomical variants of the hepatic artery may have important implications for pancreatic cancer surgery. The aim of our study is to compare the outcome following a pancreatoduodenectomy (PD) in patients with or without a variant hepatic artery arising from superior mesenteric artery. Material and methods: We reviewed 151 patients with periampullary tumoral pathology. All patients underwent oncological PD between January 2005 and February 2012. Our series was divided into two groups: Group A: Patients with a hepatic artery arising from superior mesenteric artery; and Group B: Patients without a hepatic artery arising from superior mesenteric artery. We expressed the results as mean ± standard deviation for continuous variables and percentages for qualitative variables. Statistical tests were considered significant if p < 0.05. Results: We identified 11 patients with a hepatic artery arising from superior mesenteric artery (7.3%). The most frequent variant was an aberrant right hepatic artery (n = 7), following by the accessory right hepatic artery (n = 2) and the common hepatic artery trunk arising from the superior mesenteric artery (n = 2). In 73% of cases the diagnosis of the variant was intraoperative. R0 resection was performed in all patients with a hepatic artery arising from superior mesenteric artery. There were no significant differences in the tumor resection margins and the incidence of postoperative complications. Conclusion: Oncological PD is feasible by the presence of a hepatic artery arising from superior mesenteric artery. The complexity of having it does not seem to influence in tumor resection margins, complications and survival

Post-transplant lymphoproliferative disease in liver transplant recipients

Post-transplant lymphoproliferative syndrome (PTLD) is a rare and potentially life-threatening complication after liver transplantation. The aim of this study was to analyze the clinicopathologic features related to PTLD in a single institution after liver transplantation. Observational study where we have retrospectively analyzed 851 cases who underwent liver transplantation. Ten cases have developed PTLD. Their clinical-pathological characteristics and the treatment received have been analyzed. PTLD incidence was 1.2% (10/851). The mean time from liver transplantation to PTLD diagnosis was 36 months (range 1.2 to 144 months). PTLD localization was extranodal in all cases, the most frequent location being intestinal. Seven cases showed a monomorphic lymphoma which in all cases was differentiated B cell lymphomas. Fifty per cent of the series were seropositive for Epstein-Barr virus. Five patients were alive at the time of the review. Among these patients, we observed three cases of complete remission and two cases of disease stabilization. The death rate was higher in the first year after diagnosis of PTLD. PTLD is a rare complication after liver transplantation, but it may pose a threat to the life of a liver transplant recipient. It is essential to identify patients at risk, to establish an early diagnosis and treatment that can change the outcome of the disease

Translational pancreatic cancer research: A comparative study on patient-derived xenograft models.

To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic). Histological analysis (haematoxylin-eosin and Masson's trichrome staining) and immunohistochemical assessment of apoptosis (TUNEL), proliferation (Ki-67), angiogenesis (CD31) and fibrogenesis (α-SMA) were performed. When a tumour xenograft reached the target size, it was re-implanted in a new nude mouse. Three sequential tumour xenograft generations were generated (F1, F2 and F3). The overall tumour engraftment rate was 61.1%. The subcutaneous model was most effective in terms of tissue growth (69.9%), followed by intraperitoneal (57.6%) and pancreatic (55%) models. Tumour development was faster in the subcutaneous model (17.7 ± 2.6 wk) compared with the pancreatic (23.1 ± 2.3 wk) and intraperitoneal (25.0 ± 2.7 wk) models (P = 0.064). There was a progressive increase in the tumour engraftment rate over successive generations for all three models (F1 28.1% vs F2 71.4% vs F3 80.9%, P In our experience, the faster development and greatest number of viable xenografts could make the subcutaneous model the best option for experimentation in pancreatic cancer

SARS-CoV-2 vaccination modelling for safe surgery to save lives: Data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population