Cell-specific Extracellular Vesicles and Their miRNA Cargo Released Into the Organ Preservation Solution During Cold Ischemia Storage as Biomarkers for Liver Transplant Outcomes.

BACKGROUND: Liver transplantation (LT) is crucial for end-stage liver disease patients, but organ shortages persist. Donation after circulatory death (DCD) aims to broaden the donor pool but presents challenges. Complications like acute rejection, hepatic artery thrombosis, and biliary issues still impact posttransplant prognosis. Biomarkers, including extracellular vesicles (EVs) and microRNAs (miRNAs), show promise in understanding and monitoring posttransplant events. This study explores the role of EVs and their miRNA cargo in LT, including their potential as diagnostic tools. METHODS: EVs from intrahepatic end-ischemic organ preservation solution (eiOPS) in 79 donated livers were detected using different techniques (nanosight tracking analysis, transmission electron microscopy, and flow cytometry). EV-derived miRNAs were identified by quantitative real time-polymerase chain reaction. Bioinformatics analysis was performed using the R platform. RESULTS: Different-sized and origin-specific EVs were found in eiOPS, with significantly higher concentrations in DCD compared with donation after brain death organs. Additionally, several EV-associated miRNAs, including let-7d-5p, miR-28-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429, were overexpressed in DCD-derived eiOPS. These miRNAs also exhibited differential expression patterns in liver tissue biopsies. Pathway analysis revealed enrichment in signaling pathways involved in extracellular matrix organization and various cellular processes. Moreover, specific EVs and miRNAs correlated with clinical outcomes, including survival and early allograft dysfunction. A predictive model combining biomarkers and clinical variables showed promise in acute rejection detection after LT. CONCLUSIONS: These findings provide new insights into the use of EVs and miRNAs as biomarkers and their possible influence on posttransplantation outcomes, potentially contributing to improved diagnostic approaches and personalized treatment strategies in LT.

Neoadjuvant Chemotherapy plus Interval Cytoreductive Surgery with or without Hyperthermic Intraperitoneal Chemotherapy (NIHIPEC) in the Treatment of Advanced Ovarian Cancer: A Multicentric Propensity Score Study.

INTRODUCTION: Epithelial ovarian cancer (EOC) is primarily confined to the peritoneal cavity. When primary complete surgery is not possible, neoadjuvant chemotherapy (NACT) is provided; however, the peritoneum-plasma barrier hinders the drug effect. The intraperitoneal administration of chemotherapy could eliminate residual microscopic peritoneal tumor cells and increase this effect by hyperthermia. Intraperitoneal hyperthermic chemotherapy (HIPEC) after interval cytoreductive surgery could improve outcomes in terms of disease-free survival (DFS) and overall survival (OS). MATERIALS AND METHODS: A multicenter, retrospective observational study of advanced EOC patients who underwent interval cytoreductive surgery alone (CRSnoH) or interval cytoreductive surgery plus HIPEC (CRSH) was carried out in Spain between 07/2012 and 12/2021. A total of 515 patients were selected. Progression-free survival (PFS) and OS analyses were performed. The series of patients who underwent CRSH or CRSnoH was balanced regarding the risk factors using a statistical analysis technique called propensity score matching. RESULTS: A total of 170 patients were included in each subgroup. The complete surgery rate was similar in both groups (79.4% vs. 84.7%). The median PFS times were 16 and 13 months in the CRSH and CRSnoH groups, respectively (Hazard ratio (HR) 0.74; 95% CI, 0.58-0.94; p = 0.031). The median OS times were 56 and 50 months in the CRSH and CRSnoH groups, respectively (HR, 0.88; 95% CI, 0.64-1.20; p = 0.44). There was no increase in complications in the CRSH group. CONCLUSION: The addition of HIPEC after interval cytoreductive surgery is safe and increases DFS in advanced EOC patients.

Endothelial cell activation mediated by cold ischemia-released mitochondria is partially inhibited by defibrotide and impacts on early allograft function following liver transplantation.

DAMPs (danger-associated molecular patterns) are self-molecules of the organism that appear after damage. The endothelium plays several roles in organ rejection, such as presenting alloantigens to T cells and contributing to the development of inflammation and thrombosis. This study aimed to assess whether DAMPs present in the organ preservation solution (OPS) after cold ischemic storage (CIS) contribute to exacerbating the endothelial response to an inflammatory challenge and whether defibrotide treatment could counteract this effect. The activation of cultured human umbilical vein endothelial cells (HUVECs) was analyzed after challenging with end-ischemic OPS (eiOPS) obtained after CIS. Additionally, transwell assays were performed to study the ability of eiOPS to attract lymphocytes across the endothelium. The study revealed that eiOPS upregulated the expression of MCP-1 and IL-6 in HUVECs. Moreover, eiOPS increased the membrane expression of ICAM-1and HLA-DR, which facilitated leukocyte migration toward a chemokine gradient. Furthermore, eiOPS demonstrated its chemoattractant ability. This activation was mediated by free mitochondria. Defibrotide was found to partially inhibit the eiOPS-mediated activation. Moreover, the eiOPS-mediated activation of endothelial cells (ECs) correlated with early allograft dysfunction in liver transplant patients. Our finding provide support for the hypothesis that mitochondria released during cold ischemia could trigger EC activation, leading to complications in graft outcomes. Therefore, the analysis and quantification of free mitochondria in the eiOPS samples obtained after CIS could provide a predictive value for monitoring the progression of transplantation. Moreover, defibrotide emerges as a promising therapeutic agent to mitigate the damage induced by ischemia in donated organs.

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

Goiter surgery recommendations in sub-Saharan Africa in humanitarian cooperation.

Background: The standard treatment for endemic goiter is usually total thyroidectomy. In low- and middle-income countries, the management of thyroid disease, which is commonplace in fully developed countries, is not always possible. The purpose of this study is to establish a treatment algorithm to calculate the extent of thyroidectomy based on the risk factors of each patient. Methods: This is a retrospective observational study conducted during the period between 2017 and 2019. A total of 287 patients with thyroid pathology were treated in Maragua Hospital (Kenya). The results of surgical treatment were analyzed after the implementation of an individualized treatment protocol. Results: One hundred and sixty patients with different types of goiter underwent surgery: solitary nodule (54.4%), multi-nodular goiter (30.6%), diffuse goiter (10.6%), and intrathoracic goiter (3.8%). The techniques used were hemithyroidectomy (78.8%), Dunhill thyroidectomy (9.4%), bilateral subtotal thyroidectomy (6.9%), and total thyroidectomy (3.1%). There was no mortality. The surgical morbidity rate was 16% (only one major complication (3b)). Two cases of dysphonia were resolved in the first week. There were three cases of symptomatic hypocalcaemia, two of which resolved in the first week and the other of which was definitive. The follow-up at 6 months was 67%. The cancer rate found in the resection specimens was 5%. Discussion: The implementation of individualized surgical protocols for thyroid surgery in sub-Saharan Africa can improve outcomes. The cooperation projects can increase access to complex surgical treatment for patients with limited resources in low- and middle-income countries.

The impact of information and communications technology and broadcasting on YouTube for improving attitude toward organ donation in secondary education with the creation of short films.

OBJECTIVE: There is a lack of awareness about organ donation among teenagers, a fact that could decrease future donation rates. The objective is to analyze the impact of an educational proposal based on the creation of short films. METHODS: Fifteen schools were randomly selected: ten for the experimental group (EG), and five for the control group (CG). In both groups all students from the selected classes participated (EG: n = 543, CG: n = 320). An intervention was undertaken in the EG, providing a website to make a short film about organ donation and transplantation (ODT) to be broadcast on YouTube. The students completed a questionnaire before and after the proposal. STATISTICS: Mann-Whitney test was conducted to compare the pre-test data, McNemar test compare the pre and post test results of each group, and Chi-square test to compare the change in responses between the two groups. RESULTS: The change to a more favorable response was greater in the EG in all variables. The YouTube channel received 104,912 viewings. CONCLUSIONS: An innovative educational intervention has a positive influence on teenage attitude and knowledge about ODT; it also has important social repercussions. PRACTICE IMPLICATIONS: Implementing this educational proposal about ODT could help improve future donation rates.

¿Está indicada la gastrectomía profiláctica en pacientes sanos portadores del gen CDH1 para el cáncer gástrico difuso hereditario? / Is prophylactic gastrectomy indicated for healthy carriers of CDH1 gene mutations associated with hereditary diffuse gastric cancer?

Introducción: el cáncer gástrico difuso hereditario (CGDH) constituye uno de los síndromes de cáncer hereditario recientemente comunicados. Aquellos pacientes con sospecha de CGDH deben ser vigilados con endoscopia y toma múltiples de biopsias. Como alternativa, algunos autores proponen la realización de gastrectomía profiláctica (GP) en los portadores de la enfermedad. El objetivo de este trabajo es presentar nuestra experiencia con una familia portadora de la mutación CDH1 a los que se realizó una GP. Pacientes y métodos: nuestro caso índice corresponde a una mujer de 34 años que se diagnosticó de un adenocarcinoma gástrico difuso con carcinomatosis masiva. Presentaba antecedentes familiares de adenocarcinoma gástrico en siete ascendientes. Se realizó un estudio genético mediante secuenciación de CDH1, en el cual se encontró la mutación c1577G>A en el exón 11 del gen CDH1. Resultados: esta mutación estaba también presente en otros seis familiares de la paciente, a los que se les realizó una gastrectomía profiláctica. La anatomía patológica de los estómagos de estos pacientes informó de múltiples focos microscópicos de adenocarcinoma en cinco de ellos, a pesar de que en las numerosas endoscopias realizadas antes de la cirugía no fueron detectados. Conclusiones: recomendamos realizar una gastrectomía profiláctica en los pacientes portadores del gen CDH1 a pesar de ausencia de lesiones tumorales en el screening endoscópico

Introduction: hereditary diffuse gastric cancer (HDGC) is a recently reported hereditary cancer syndrome. Patients with suspected HDGC must be under surveillance via endoscopy and multiple biopsies. As an alternative, some studies suggest prophylactic gastrectomy (PG) for disease carriers. The goal of this article was to report our experience with a CDH1 mutation positive family who underwent PG. Patients and methods: the index case was a 34-year-old female diagnosed with diffuse gastric adenocarcinoma and massive carcinomatosis. There was a family history of gastric adenocarcinoma in seven family members. A genetic study identified the c.1577G>A mutation, in exon 11 of the CDH1 gene via sequencing analysis. Results: this mutation was also present in other six family members, who subsequently underwent prophylactic gastrectomy. The pathology study of resected gastric segments revealed multiple microscopic foci of adenocarcinoma in five of these individuals. These foci were not detected in the multiple endoscopies performed before surgery. Conclusions: we recommend prophylactic gastrectomy for CDH1 mutation carriers even in the absence of lesions during endoscopic screening

Is prophylactic gastrectomy indicated for healthy carriers of CDH1 gene mutations associated with hereditary diffuse gastric cancer?

INTRODUCTION: hereditary diffuse gastric cancer (HDGC) is a recently reported hereditary cancer syndrome. Patients with suspected HDGC must be under surveillance via endoscopy and multiple biopsies. As an alternative, some studies suggest prophylactic gastrectomy (PG) for disease carriers. The goal of this article was to report our experience with a CDH1 mutation positive family who underwent PG. PATIENTS AND METHODS: the index case was a 34-year-old female diagnosed with diffuse gastric adenocarcinoma and massive carcinomatosis. There was a family history of gastric adenocarcinoma in seven family members. A genetic study identified the c.1577G>A mutation, in exon 11 of the CDH1 gene via sequencing analysis. RESULTS: this mutation was also present in other six family members, who subsequently underwent prophylactic gastrectomy. The pathology study of resected gastric segments revealed multiple microscopic foci of adenocarcinoma in five of these individuals. These foci were not detected in the multiple endoscopies performed before surgery. CONCLUSIONS: we recommend prophylactic gastrectomy for CDH1 mutation carriers even in the absence of lesions during endoscopic screening.

Rotura espontánea de aneurisma de arteria esplénica en el síndrome de Ehlers-Danlos tipo clásico / Spontaneous rupture of a splenic aneurysm in classic Ehlers-Danlos syndrome

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Colecistitis aguda enfisematosa de curso fulminante tras cirugía cardiaca / Acute fulminating emphysematous cholecystitis after cardiac surgery

No disponible

2-methoxyestradiol in the pathophysiology of endometriosis: focus on angiogenesis and therapeutic potential.

Endometriosis is a common condition among women of childbearing potential in which ectopic endometrial tissue is found outside the uterine cavity. Neoangiogenesis plays a major role in the development of endometriotic implants. Some evidence suggests that a disorder in the balance of proangiogenic and antiangiogenic factors that favors the former is induced by local hypoxia and is mediated by the hypoxia-inducible factor-vascular endothelium growth factor pathway could partially explain the development of this condition in some women. 2-methoxyestradiol is a biologically active metabolite of estradiol having antiangiogenic action. Changes in estradiol homeostasis have been locally observed in endometriosis. In this review, we summarize current knowledge of endometriosis pathophysiology, in particular, the balance between local 2-methoxyestradiol production and angiogenesis, which could promote the development of endometriotic lesions. 2-Methoxyestradiol emerges as a promising new candidate for the treatment of endometriosis.

Cirugía del tracto urinario en pacientes con carcinomatosis peritoneal ovárica tratadas con citorreducción y quimioterapia intraperitoneal intraoperatoria hipertérmica / Urinary tract surgery in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy

Introducción El objetivo del presente trabajo es describir nuestra experiencia en la cirugía del uréter y la vejiga en pacientes con carcinoma de ovario primario y recurrente sometidas a procedimientos de peritonectomía y administración de quimioterapia intraperitoneal intraoperatoria hipertérmica (HIPEC).Pacientes y método Sobre una base de datos prospectiva construida al comienzo del programa de carcinomatosis peritoneal en nuestro centro, se seleccionaron aquellas pacientes en las que fue preciso realizar maniobras quirúrgicas sobre uréter distal o la vejiga. Siete pacientes cumplían este requisito y fueron incluidas en el estudio. Desde diciembre de 2007 hasta abril de 2011 fueron incluidas para la realización de citorredución de máximo esfuerzo y HIPEC 81 pacientes diagnosticadas de carcinoma de ovario primario o recurrente. Resultados En siete pacientes, con una mediana de edad de 46 años (40-71), fue necesaria la realización de algún gesto quirúrgico sobre el uréter o la vejiga. Cuatro pacientes fueron intervenidas por recurrencia de la enfermedad ovárica y en otras 3 pacientes la indicación fue el rescate quirúrgico, tras cirugía no óptima en otro centro. En 4 de ellas existía afectación tumoral directa del tracto urinario inferior. Tres pacientes (42%) de la serie desarrollaron al menos una complicación postoperatoria. Conclusión La realización de procedimientos de peritonectomía que incluye la eventual resección del uréter o la vejiga y la posterior aplicación de HIPEC en un grupo seleccionado de pacientes con diseminación peritoneal por carcinoma de ovario puede realizarse con cifras razonables de morbilidad postoperatoria. Estos gestos quirúrgicos pueden ser necesarios para la consecución de una cirugía óptima (AU)

Introduction The objective of the present work is to describe our experience in the surgery of the ureter and bladder in patients with primary and recurrent ovarian cancer subjected to peritonectomy procedures and the administration of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC).Patients and method Those patients who required surgical procedures on the distal ureter or bladder, were selected from a prospective data base constructed at the beginning of the peritoneal carcinomatosis program in our centre. Seven patients fulfilled this requirement and were included in the study. A total of 81 patients diagnosed with primary or recurrent ovarian cancer from December 2007 to April 2011 were included for maximum effort cytoreduction and HIIC. ResultsIt was necessary to perform some surgical manoeuvre on the ureter or bladder in seven patients, with a median age of 46 years (40-71). Four patients were operated on due to recurrence of the ovarian disease and in the other 3 patients the indication was surgical rescue after non-optimal surgery in another centre. There was direct tumour involvement of the lower urinary tract in 4 of them. Three patients (42%) in the series developed at least one postoperative complication. Conclusion The performing of peritonectomy procedures that include the eventual resection of the ureter or bladder, and the subsequent application of HIIC in a selected group of patients with peritoneal dissemination due to an ovarian carcinoma can be done with reasonable rates of postoperative morbidity. These surgical procedures may be necessary to achieve optimal surgery (AU)

[Urinary tract surgery in patients with ovarian peritoneal carcinomatosis treated with cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy]. / Cirugía del tracto urinario en pacientes con carcinomatosis peritoneal ovárica tratadas con citorreducción y quimioterapia intraperitoneal intraoperatoria hipertérmica.

INTRODUCTION: The objective of the present work is to describe our experience in the surgery of the ureter and bladder in patients with primary and recurrent ovarian cancer subjected to peritonectomy procedures and the administration of hyperthermic intraoperative intraperitoneal chemotherapy (HIIC). PATIENTS AND METHOD: Those patients who required surgical procedures on the distal ureter or bladder, were selected from a prospective data base constructed at the beginning of the peritoneal carcinomatosis program in our centre. Seven patients fulfilled this requirement and were included in the study. A total of 81 patients diagnosed with primary or recurrent ovarian cancer from December 2007 to April 2011 were included for maximum effort cytoreduction and HIIC. RESULTS: It was necessary to perform some surgical manoeuvre on the ureter or bladder in seven patients, with a median age of 46 years (40-71). Four patients were operated on due to recurrence of the ovarian disease and in the other 3 patients the indication was surgical rescue after non-optimal surgery in another centre. There was direct tumour involvement of the lower urinary tract in 4 of them. Three patients (42%) in the series developed at least one postoperative complication. CONCLUSION: The performing of peritonectomy procedures that include the eventual resection of the ureter or bladder, and the subsequent application of HIIC in a selected group of patients with peritoneal dissemination due to an ovarian carcinoma can be done with reasonable rates of postoperative morbidity. These surgical procedures may be necessary to achieve optimal surgery.

Tolerancia inmunológica en el trasplante hepático / No disponible

No disponible

[Spirometric evaluation of respiratory involvement in asymptomatic multinodular goiter with an intrathoracic component]. / Valoración espirométrica de la afectación respiratoria en el bocio multinodular asintomático con componente intratorácico.

Respiratory tract obstruction is underestimated in asymptomatic intrathoracic goiter. Our aim was to evaluate the involvement of the upper airway of asymptomatic patients with intrathoracic multinodular goiter, assessing the effect on respiratory function by means of spirometry. We selected 21 patients with asymptomatic intrathoracic goiter on whom a thyroidectomy had been performed. Spirometry was done in supine decubitus and in standing position before and 3 months after surgery. The preoperative study in decubitus showed mild obstruction in 4 cases (20%). In 2 of these cases this condition was also present in standing position (10%). Spirometry became normal after surgery in the 4 patients with obstruction. To conclude, spirometry in asymptomatic intrathoracic goiter shows mild obstruction of respiratory function in 10% to 20% of cases, depending on position. Surgery was associated with normalization of the abnormal parameters and an improvement in the remaining parameters. These data support the need to schedule surgery as soon as possible.

Valoración espirométrica de la afectación respiratoria en el bocio multinodular asintomático con componente intratorácico / Spirometric evaluation of respiratory involvement in asymptomatic multinodular goiter with an intrathoracic component

La obstrucción de la vía aérea se infravalora en el bocio intratorácico asintomático. Nuestro objetivo ha sido valorar mediante espirometría la afectación de la vía aérea superior y la repercusión en la función respiratoria de pacientes asintomáticos con bocio multinodular intratorácico. Para ello se seleccionó prospectivamente a 21 pacientes con bocio intratorácico asintomático a quienes se había practicado una tiroidectomía. Se realizó la espirometría en decúbito supino y en bipedestación antes y a los 3 meses de la cirugía. El estudio preoperatorio mostró en decúbito una afectación obstructiva leve en 4 casos (20%), en 2 de los cuales persistía en bipedestación (10%). Tras la cirugía se normalizó la alteración en los 4 casos. En conclusión, la espirometría en el bocio intratorácico asintomático muestra una afectación obstructiva leve de la función respiratoria en el 10-20% de los casos, en función de la postura. La cirugía se acompaña de la normalización de los parámetros alterados y de la mejoría del resto. Estos datos apoyan la necesidad de indicar la cirugía lo antes posible (AU)

Respiratory tract obstruction is underestimated in asymptomatic intrathoracic goiter. Our aim was to evaluate the involvement of the upper airway of asymptomatic patients with intrathoracic multinodular goiter, assessing the effect on respiratory function by means of spirometry. We selected 21 patients with asymptomatic intrathoracic goiter on whom a thyroidectomy had been performed. Spirometry was done in supine decubitus and in standing position before and 3 months after surgery. The preoperative study in decubitus showed mild obstruction in 4 cases (20%). In 2 of these cases this condition was also present in standing position (10%). Spirometry became normal after surgery in the 4 patients with obstruction. To conclude, spirometry in asymptomatic intrathoracic goiter shows mild obstruction of respiratory function in 10% to 20% of cases, depending on position. Surgery was associated with normalization of the abnormal parameters and an improvement in the remaining parameters. These data support the need to schedule surgery as soon as possible (AU)