Safety and Effectiveness of Perioperative Hyperthermic Intraperitoneal Chemotherapy with Gemcitabine in Patients with Resected Pancreatic Ductal Adenocarcinoma: Clinical Trial EudraCT 2016-004298-41.

BACKGROUND: Despite the improvement in therapies, pancreatic cancer represents one of the most cancer-related deaths. In our hypothesis, we propose that Hyperthermic Intraperitoneal Chemotherapy with gemcitabine after pancreatic cytoreductive surgery could reduce tumor progression by reducing residual neoplastic volume and residual pancreatic cancer stem cells. MATERIALS AND METHODS: A randomized trial involving 42 patients. All patients were diagnosed with pancreatic ductal adenocarcinoma. Group I: R0 resection. Group II. R0 resection and HIPEC with gemcitabine (120 mg/m2 for 30 min). Effectiveness was measured with analysis of overall survival, disease-free survival, distant recurrence, locoregional recurrence, and measuring of pancreatic cancer stem cells (EpCAM+CXCR4+CD133+). RESULTS: From 2017 to 2023, 63 patients were recruited for our clinical trial; 21 patients were included in each group, and 21 were excluded. Locoregional recurrence, p-value: 0.022, was lower in the experimental group. There were no significant differences between the two groups in hospital mortality, perioperative complications, or hospital costs. We found a significant decrease in pancreatic cancer stem cells in patients in the experimental group after treatment, p -value of 0.018. CONCLUSIONS: The use of HIPEC with gemcitabine after surgery in patients with resectable pancreatic ductal adenocarcinoma reduces locoregional recurrence and may be associated with a significant decrease in pancreatic cancer stem cells.

Paclitaxel as HIPEC-Drug after Surgical Cytoreduction for Ovarian Peritoneal Metastases: A Randomized Phase III Clinical Trial (HIPECOVA).

Multidisciplinary strategies have transformed the management of advanced ovarian cancer. We aimed to evaluate the effectiveness of paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical cytoreduction for ovarian peritoneal metastases in a randomized phase III trial conducted between August 2012 and December 2019. Seventy-six patients were randomized to either the HIPEC or no HIPEC group. Although median values for the primary endpoints (recurrence-free survival (RFS) and overall survival (OS)) revealed superior outcomes for the HIPEC (RFS: 23 months, OS: 48 months) over the control group (RFS: 19 months, OS: 46 months), these differences were not statistically significant (p = 0.22 and p = 0.579). Notably, the HIPEC group demonstrated significantly higher 5-year OS and 3-year RFS rates (47.2% and 47.5%) compared to patients without HIPEC (34.5% and 21.3%). Stratification according to Peritoneal Surface Disease Severity Score (PSDSS) showed improved OS and RFS for patients with lower PSDSS (I-II) in the HIPEC-treated group (p = 0.033 and p = 0.042, respectively). The Clavien-Dindo classification of adverse event grades revealed no significant differences between HIPEC and controls (p = 0.482). While overall results were not statistically significant, our long-term follow-up emphasized the potential benefit of HIPEC-associated cytoreduction with paclitaxel, particularly in selected ovarian cancer patients with lower PSDSS indices.

Evaluation of Parameters Which Influence Voluntary Ingestion of Supplements in Rats.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based supplements in rats, assessing the influence of age, sex, fasting (4 h), and additives (vanilla, VF; sucralose, S), and to test it in lactating dams. Three-week-old and 5-month-old Sprague-Dawley rats were placed individually in an empty cage containing a gelatin cube and trained daily (5 days/week), recording the day the whole cube was consumed (latency). Rats trained prior to gestation were offered a gelatin containing 250 mg/kg cocoa shell extract (CSE) during lactation. Rats that did not eat the cube after 8 training days were considered non-habituated, with a proportion similar in young males (7.1%), young females (11.1%), and adult females (10.3%), but significantly higher in adult males (39.3%). Excluding non-habituated rats, latency was 2-3 days, without differences between young and adult rats (p = 0.657) or between males and females (p = 0.189). VF or VF + S in the gelatin did not modify latency, while fasting significantly reduced it in females (p = 0.007) but not in males (p = 0.501). During lactation, trained females ate the CSE-gelatin within 1-5 min without litter problems. Conclusions: Acceptance of a gelatin-based supplement is negatively influenced by male sex, facilitated by fasting, and not modified by additives. Training is remembered after 2 months and does not interfere with lactation. Gelatin-based voluntary ingestion is suitable to administer drugs that need to pass through the digestive system, ensuring adequate dosage, and is important to detect non-habituated rats prior to the study. The current protocol may be implemented by training the rats in their own cage.

The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.

The Homogeneous Azorean Machado-Joseph Disease Cohort: Characterization and Contributions to Advances in Research.

Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia worldwide. MJD is characterized by late-onset progressive cerebellar ataxia associated with variable clinical findings, including pyramidal signs and a dystonic-rigid extrapyramidal syndrome. In the Portuguese archipelago of the Azores, the worldwide population cluster for this disorder (prevalence of 39 in 100,000 inhabitants), a cohort of MJD mutation carriers belonging to extensively studied pedigrees has been followed since the late 1990s. Studies of the homogeneous Azorean MJD cohort have been contributing crucial information to the natural history of this disease as well as allowing the identification of novel molecular biomarkers. Moreover, as interventional studies for this globally rare and yet untreatable disease are emerging, this cohort should be even more important for the recruitment of trial participants. In this paper, we profile the Azorean cohort of MJD carriers, constituted at baseline by 20 pre-ataxic carriers and 52 patients, which currently integrates the European spinocerebellar ataxia type 3/Machado-Joseph disease Initiative (ESMI), a large European longitudinal MJD cohort. Moreover, we summarize the main studies based on this cohort and highlight the contributions made to advances in MJD research. Knowledge of the profile of the Azorean MJD cohort is not only important in the context of emergent interventional trials but is also pertinent for the implementation of adequate interventional measures, constituting relevant information for Lay Associations and providing data to guide healthcare decision makers.

Consensus of the Respiratory Committee of the Latin American Society for Pediatric Intensive Care: Management of pediatric SARS-CoV-2. (SLACIP): COVID-19 Pediatric / Consenso del Comité Respiratorio Sociedad Latinoamericana Terapia Intensiva Pediátrica: Manejo SARS-CoV-2 pediátrico. (SLACIP): COVID-19 Pediátrico

Introduction The COVID-19 pandemic generated many controversies in the management of critically ill pediatric patients. The main ones were about ventilatory support, phenotypic differences between adults and children, and acute and subacute clinical forms. For this reason, the Respiratory Committee (RC) of the Latin American Society of Pediatric Intensive Care (SLACIP) generated a document to summarize the recommendations with the best evidence. The objective of these recommendations is to provide an update on issues related to pediatric COVID-19. Methods and Materials The Respiratory Committee created a group composed of 19 pediatric kinesiologists/physiotherapists and intensivists from 8 Latin American countries and defined on 3/27/20 the 15 most relevant topics, assigning 3 referents and 2 reviewers for each. The manuscripts went through 4 stages until their final version. The complete document was freely distributed on 22/05/20 and updated twice (07/08/20 and 02/09/21). For the current version there were 3 special collaborators. Result The material consists of a complete 94-page document and an executive summary. The topics included are case definition, epidemiology, clinical classification, subacute inflammatory syndrome, personal protective equipment, aerosolization situations (intubation, extubation, suctioning, sampling, filter replacement, cardiopulmonary resuscitation, early mobilization), high flow cannula support, invasive, non-invasive and high frequency mechanical ventilation, pharmacological treatment, laboratory and imaging. Conclusion The purpose of this document is to serve as a guide for nurses, kinesiologists/physiotherapists and physicians in the management of critically ill pediatric patients with COVID-19.

Introducción La pandemia por COVID-19 generó muchas controversias en el manejo de los pacientes pediátricos críticos. Las principales fueron sobre el soporte ventilatorio, las diferencias fenotípicas entre adultos y niños y las formas clínicas aguda y subaguda.Por esa razón el Comité Respiratorio (CR) de la Sociedad Latinoamericana de Cuidados Intensivos Pediátricos (SLACIP) generó un documento para resumir las recomendaciones con mayor evidencia. El objetivo de estas recomendaciones es brindar una actualización de temas relacionados a COVID-19 pediátrico.Métodos y Materiales El Comité Respiratorio creó un grupo compuesto por 19 kinesiólogos/fisioterapeutas y médicos intensivistas pediátricos de 8 países de Latinoamérica y definió el 27/03/20 los 15 temas más relevantes, asignando 3 referentes y 2 revisores por cada uno. Los manuscritos pasaron por 4 etapas hasta su versión final. El documento completo se distribuyó libremente el 22/05/20, actualizándose en dos oportunidades (07/08/20 y el 02/09/21). Para la versión actual se contó con 3 colaboradores especiales.Resultado El material se compone de un documento completo de 94 páginas y un resumen ejecutivo. Los temas incluidos son definición de caso, epidemiología, clasificación clínica, síndrome inflamatorio subagudo, equipos de protección personal, situaciones de aerosolización (intubación, extubación, aspiración, toma de muestras, recambio de filtros, reanimación cardiopulmonar, movilización temprana), soporte con cánula de alto flujo, ventilación mecánica invasiva, no invasiva y de alta frecuencia, tratamiento farmacológico, laboratorio e imágenes.Conclusión La elaboración de este documento ha tenido como fin servir de guía para enfermeros, kinesiólogos/fisioterapeutas y médicos en el manejo de pacientes pediátricos en estado crítico por COVID-19.

Preparation of Nanofibers Mats Derived from Task-Specific Polymeric Ionic Liquid for Sensing and Catalytic Applications.

Nanofibers mats derived from the task-specific functionalized polymeric ionic liquids based on homocysteine thiolactone are obtained by electrospinning them as blends with polyvinylpyrrolidone. The presence of this functional moiety allowed the post-functionalization of these mats through the aminolysis of the thiolactone ring in the presence of an amine by a thiol-alkene "click" reaction. Under controlled experimental conditions the modification can be performed introducing different functionalization and crosslinking of the electrospun fibers, while maintaining the nanostructure obtained by the electrospinning. Initial studies suggest that the nanofibers based on these functionalized polymeric ionic liquids can be used in both sensing and catalytic applications.

Safety of perioperative hyperthermic intraperitoneal chemotherapy with gemcitabine in patients with resected pancreatic adenocarcinoma: a pilot study of the clinical trial EudraCT 2016-004298-41.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with gemcitabine, after cytoreductive surgery, may reduce the tumor progression of pancreatic cancer through the reduction of the neoplastic volume and the subpopulation of residual pancreatic cancer stem cells, improving the survival of patients with pancreatic cancer and decreasing the recurrence of the disease. METHODS: A pilot study is performed with the first ten patients in the experimental group. A randomized study (phase II-III clinical trial) that requires a population of 42 patients, with 21 patients in each group. All patients have a diagnosis of ductal adenocarcinoma of the pancreas, which will be surgically resected with curative intention. (I) Group I: after an R0 resection, patients receive individualized adjuvant treatments. (II) Group II: after an R0 resection, HIPEC is performed with gemcitabine (120 mg/m2 for 30 min), and they also receive individualized adjuvant treatments. To analyze the safety of the procedure, the main variables measured were as follows: grades of complications by means of the Clavien-Dindo system: pancreas surgery complications (e.g., pancreatic fistula, perioperative hemorrhage, delayed gastric emptying, biliary fistula), operative mortality, and laboratory parameters to control system functions. Values were measured three times: preoperatively, twenty-four hours after surgery, and on the 7th postoperative day. RESULTS: From 2018 to 2019, 31 patients were recruited for our clinical trial. Fifteen patients were excluded because of intraoperative unresectability or a different intraoperative histologic diagnosis. Ten patients were included in the experimental group (resection plus HIPEC gemcitabine). The mean age was 65±7 years, and six patients were female (60%). We confirmed the histologic diagnosis of ductal pancreatic adenocarcinoma in all patients prior to HIPEC. Total pancreatectomy was performed in five patients. The surgical median time was 360 min, and the hospital stay was 11 days. Four patients showed complications classified as Clavien-Dindo type II and one showing type I. Six patients were classified as having stage III tumors. To date, no hospital mortality, locoregional recurrence, or differences between the two groups in terms of perioperative complications, biochemical and gasometric values, or Clavien-Dindo complication grades were observed. CONCLUSIONS: Our clinical pilot study demonstrated a similar perioperative outcome that allows the trial until main objectives are achieved.

Correction: Free ion diffusivity and charge concentration on cross-linked polymeric ionic liquid iongel films based on sulfonated zwitterionic salts and lithium ions.

Correction for 'Free ion diffusivity and charge concentration on cross-linked polymeric ionic liquid iongel films based on sulfonated zwitterionic salts and lithium ions' by David Valverde et al., Phys. Chem. Chem. Phys., 2019, 21, 17923-17932, DOI: 10.1039/C9CP01903K.

Variante anatómica sintomática de la duplicación de la vía biliar común tipo IV.

INTRODUCTION: Duplicity of the common bile duct is an unusual congenital disorder. CASE REPORT: A 80-year-old woman with duplication of the common bile duct with retrograde endoscopic cholangiopancreatography (ERCP) who did not resolve the symptoms. DISCUSSION: Our case is a variant of type IV to the classification of duplicity of the common bile duct. The magnetic resonance cholangiography and presurgical ERCP allows assessment of the bile ducts, their caliber, and assessment of abnormalities. The treatment before duplicity of the common bile duct will depend on the clinic and the type of opening of the accessory common bile duct. CONCLUSIONS: It is important to perform a pre-surgical study and during surgery with intrasurgical cholangiography.

INTRODUCCIÓN: La duplicidad del conducto biliar común es una alteración congénita insólita. CASO CLÍNICO: Mujer de 80 años con duplicación de la vía biliar común con colangiopancreatografías retrógradas endoscópicas (CPRE) que no solventan la clínica. DISCUSIÓN: Nuestro caso es una variante del tipo IV de la clasificación de duplicidad del conducto biliar común. La colangiopancreatografía por resonancia magnética y la CPRE prequirúrgica permiten valorar las vías biliares, su calibre y sus posibles anormalidades. El tratamiento dependerá de la clínica y del tipo de apertura del conducto biliar común accesorio. CONCLUSIONES: Es importante realizar un estudio prequirúrgico y durante la cirugía con colangiografía intraoperatoria.

Anatomy variant symptomatic of the duplication of the common bile duct type IV.

INTRODUCTION: Duplicity of the common bile duct (BCBD) is an unusual congenital disorder. CASE REPORT: A 80-year-old woman with duplication of the common bile duct with retrograde endoscopic cholangiopancreatography (ERCP) who did not resolve the symptoms. DISCUSSION: Our case is a variant of type IV to the classification of DCBC. The MR cholangiography and presurgical ERCP allows assessment of the bile ducts, their caliber, and assessment of abnormalities. The treatment before DCBC will depend on the clinic and the type of opening of the CBCA. CONCLUSIONS: It is important to perform a pre-surgical study and during surgery with CIO.

INTRODUCCIÓN: La duplicidad del conducto biliar común (DCBC) es una alteración congénita insólita. CASO CLÍNICO: Mujer de 80 años con duplicación de la vía biliar común con colangiopancreatografía retrógrada endoscópica (CPRE) que no dilucida la clínica. DISCUSIÓN: Este caso es una variante del tipo IV de la clasificación de DCBC. La colangiorresonancia y la CPRE prequirúrgica permiten valorar las vías biliares, su calibre y las anormalidades. El tratamiento depende de la clínica y el tipo de apertura del conducto biliar común accesorio. CONCLUSIONES: Es importante realizar estudio prequirúrgico y durante la operación con colangiografía intraoperatoria.

Clostridium difficile causante de síndrome de distrés respiratorio agudo tras pancreatectomía total / Acute respiratory distress syndrome due to clostridium difficile after total pancreatectomy

La diarrea nosocomial, que es la adquirida en el ámbito hospitalario, suele ser producida por Clostridium difficile. Sin embargo, en raras ocasiones puede ocasionar un síndrome de distrés respiratorio. Por ello, el diagnóstico de dicha patología es difícil si no se sospecha. El tratamiento se basa en el uso de antibiótico vía oral. Se expone el caso de una paciente de 66 años con dicha patología tras la realización de pancreatectomía total.

Nosocomial (hospital-acquired) diarrhea is usually caused by Clostridium difficile. On rare occasions it can cause acute respiratory distress syndrome (ARDS). Therefore, this condition should be suspected in order to make a diagnosis. Treatment is based on oral antibiotics. We report the case of a 66-year-old female patient with ARDS secondary to Clostridium difficile colitis after total pancreatectomy.

Free ion diffusivity and charge concentration on cross-linked polymeric ionic liquid iongel films based on sulfonated zwitterionic salts and lithium ions.

The properties of various mixtures of a zwitterionic ionic liquid (ZIs-1) and LiNTf2, including their conductivity, have been studied showing how they can be adjusted through their molar composition. Conductivity tends to increase with the LiNTf2 content although it presents a minimum at the region close to the eutectic point. These mixtures also provide excellent features as liquid phases for the preparation of composite materials based on crosslinked PILs. The prepared films display excellent and tuneable properties as conducting materials, with conductivities that can be higher than 10-2 S cm-1 above 100 °C. The selected polymeric compositions show very good mechanical properties and thermal stability, even for low crosslinking degrees, along with a suitable flexibility and good transparency. The final properties of the films correlate with the composition of the monomeric mixture used and with that of the ZIs-1:LiNTf2 mixture.

Rose Bengal Immobilized on Supported Ionic-Liquid-like Phases: An Efficient Photocatalyst for Batch and Flow Processes.

The catalytic activity of Rose Bengal (RB) immobilized on supported ionic liquid (IL)-like phases was evaluated as a polymer-supported photocatalyst. In these systems, the polymer was designed to play a pivotal role. The polymeric backbone adequately modified with IL-like moieties (supported IL-like phases, SILLPs) was not just an inert support for the dye but controlled the accessibility of reagents/substrates to the active sites and provided specific microenvironments for the reaction. The structure of SILLPs could be finetuned to adjust the catalytic efficiency of the RB-SILLP composites, achieving systems that were more active and stable than the related systems in the absence of IL-like units.

Pancreatectomía con preservación duodenal en un caso de neoplasia mucinosa papilar intraductal / Pancreatectomy with duodenal preservation in a intraductal papillary mucinosus neoplasia case

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Dronedarone produces early regression of myocardial remodelling in structural heart disease.

BACKGROUND AND AIMS: Left ventricular hypertrophy (LVH) in hypertension is associated with a greater risk of sustained supraventricular/atrial arrhythmias. Dronedarone is an antiarrhythmic agent that was recently approved for the treatment of atrial fibrillation. However, its effect on early regression of LVH has not been reported. We tested the hypothesis that short-term administration of dronedarone induces early regression of LVH in spontaneously hypertensive rats (SHRs). METHODS: Ten-month-old male SHRs were randomly assigned to an intervention group (SHR-D), where animals received dronedarone treatment (100 mg/kg) for a period of 14 days, or to a control group (SHR) where rats were given vehicle. A third group with normotensive control rats (WKY) was also added. At the end of the treatment with dronedarone we studied the cardiac anatomy and function in all the rats using transthoracic echocardiogram, cardiac metabolism using the PET/CT study (2-deoxy-2[18F]fluoro-D-glucose) and cardiac structure by histological analysis of myocyte size and collagen content. RESULTS: The hypertensive vehicle treated SHR rats developed the classic cardiac pattern of hypertensive cardiomyopathy as expected for the experimental model, with increases in left ventricular wall thickness, a metabolic shift towards an increase in glucose use and increases in myocyte and collagen content. However, the SHR-D rats showed statistically significant lower values in comparison to SHR group for septal wall thickness, posterior wall thickness, ventricular mass, glucose myocardial uptake, size of left ventricular cardiomyocytes and collagen content. All these values obtained in SHR-D rats were similar to the values measured in the normotensive WKY control group. CONCLUSION: The results suggest by three alternative and complementary ways (analysis of anatomy and cardiac function, metabolism and histological structure) that dronedarone has the potential to reverse the LVH induced by arterial hypertension in the SHR model of compensated ventricular hypertrophy.

Hyperthermic chemotherapy intra-abdominal laparoscopic approach: development of a laparoscopic model using CO2 recirculation system and clinical translation in peritoneal carcinomatosis.

INTRODUCTION: Hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal carcinomatosis (PC). Laparoscopic surgery is performed in the treatment of colorectal and appendiceal cancer, and PC from diverse origin in selected patients. HIPEC management by laparoscopic approach after cytoreductive surgery (CRS) completed locoregional treatment of PC, and may be feasible and safe after appropriate patient selection. OBJECTIVE: Development of an experimental model of HIPEC by laparoscopic approach, with CO2 recirculation. Clinical translation in two patients with PC and low peritoneal cancer index. MATERIAL AND METHODS: We performed CRS in a porcine model of 5 pigs (35-38 kg) by laparoscopic approach. Laparoscopic HIPEC by CO2 recirculation system was performed; laparoscopic access was used for catheter input and output placement (Paclitaxel 175 mg/m2 for 60 min at 42 °C). The experimental variables were: blood gases, haemodynamic and intra-abdominal and central temperature. Clinical model application was performed in three cases with PC from colorectal origin. RESULTS: No statistically significant differences was found in blood gases, haemodynamic or temperature in the experimental study. In clinical study, there were no technical complications during laparoscopic-HIPEC approach, and we observed no changes in haemodynamic variables during the procedure. CONCLUSIONS: CRS and HIPEC laparoscopic model by CO2 recirculation system is safe and feasible technique in selected patients, that include low PC index, local and accessible tumour recurrences or high-risk of PC tumours.

Usefulness of thermographic analysis to control temperature homogeneity in the development and implementation of a closed recirculating CO2 chemohyperthermia model.

PURPOSE: To determine the effectiveness of thermography to control the distribution of abdominal temperature in the development of a closed chemohyperthermia model. MATERIALS AND METHODS: For thermographic analysis, we divided the abdominopelvic cavity into nine regions according to a modification of carcinomatosis peritoneal index. A difference of 2.5 °C between and within the quadrants, and thermographic colours, were used as asymmetric criteria. Preclinical study:· Rats Model: Six athymic nude rats, male, rnu/rnu. They were treated with closed technique and open technique. Porcine Model: 12 female large white pigs. Four were treated with open technique and eight with closed recirculation CO2 technique. Clinical Pilot Study, EUDRACT 2011-006319-69: 18 patients with ovarian cancer were treated with cytoreductive surgery and hyperthermia intraperitoneal chemotherapy, HIPEC, with a closed recirculating CO2 system. Thermographic control and intra-abdominal temperature assessment was performed at the baseline, when outflow temperature reached 41 °C, and at 30´. RESULTS: The thermographic images showed a higher homogeneity of the intra-abdominal temperature in the closed model respect to the open technique. The thermogram showed a temperature distribution homogeneity when starting the circulation of chemotherapy. There was correlation between the temperature thermographic map in the closed porcine model and pilot study, and reached inflow and outflow temperatures, at half time of HIPEC, of 42/41.4 °C and 42 ± 0.2/41 ± 0.8 °C, respectively. There was no significant impact to the core temperature of patients after reaching the homogeneous temperature distribution. CONCLUSIONS: To control homogeneity of temperature distribution is feasible using infra-red digital images in a closed HIPEC with CO2 recirculation.

The utility of hyperthermic intra-abdominal chemotherapy with gemcitabine for the inhibition of tumor progression in an experimental model of pancreatic peritoneal carcinomatosis, in relation to their behavior with pancreatic cancer stem cells CD133+ CXCR4.

OBJECTIVE: The origin of pancreatic cancer has been identified as a population of malignant pancreatic stem cells CD133+ CXCR4+ immunophenotype. These cells have high capacity for early locoregional invasion, being responsible for early recurrence and high mortality rates of pancreatic cancer. We propose a study for decreasing tumor progression of pancreatic cancer by reducing the volume and neoplastic subpopulation of pancreatic cancer stem cells CD133+ CXCR4+. Therefore, we develop a new therapeutic model, characterized by the application of HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with gemcitabine. DESIGN: Pancreatic tumor cell line: human cell line BxPC-3. The animal model involved 18 immunosuppressed rats 5 weeks weighing 150-200 gr. The implantation of 13 × 10(6) cells/mL was performed with homogeneous distribution in the 13 abdominopelvic quadrants according to the peritoneal carcinomatosis index (PCI) and were randomized into three treatment groups. Group I (4 rats) received intravenous saline. Group II (6 rats) received intravenous gemcitabine. Group III (8 rats) received HIPEC at 41 °C for 30 min with gemcitabine + gemcitabine IV. A histological study confirmed pancreatic cancer and immunohistochemical quantification of pancreatic cancer stem cells CD133+ CXCR4+ tumor cells. RESULTS: There was a population decline of pancreatic cancer stem cells CD133+ CXCR4+ in the HIPEC group with respect to the other two groups (p < 0.001). There was a decrease in PCI between treatment groups (p < 0.05). CONCLUSION: The initial results are encouraging since there is a declining population of cancer stem cells CD133+ CXCR4+ in the HIPEC group and decreased tumor volume compared to the other two treatment groups. All the conclusions are only valid for BxPC3 cell line, and the effects HIPEC on Kras-driven pancreatic tumors remain to be determined.