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, ).

The role of mucin cell-free DNA detection as a new marker for the study of acellular pseudomyxoma peritonei of appendicular origin by liquid biopsy.

BACKGROUND: Acellular pseudomyxoma peritonei (aPMP) is a rare peritoneal malignancy characterized by the accumulation of large amounts of mucin (lacking tumor cells) in the peritoneum. Many cases account for several kilograms of mucin to be screened by the pathologist. This is a comprehensive study of three patients with aPMP, whose tumors showed KRAS mutation, allowing for the tracking of this marker by liquid biopsy. METHODS: Pre and post-surgery plasma, and mucin removed during cytoreductive surgery were collected from the patients. KRAS mutations were analyzed using droplet digital polymerase chain reaction (ddPCR). Mucin was injected in mice. KRAS and cytokine levels were measured in plasma of the mice using ddPCR and a magnetic bead-based assay. Mucin microbiome was analyzed by 16S rRNA sequencing. RESULTS: KRAS mutations were detected in mucin cell-free DNA (cfDNA) from the three patients but not in the pre or post-surgery plasma. Electron microscopy detected microparticles (diameter <0.4 µm) in mucin. Mucin from one patient grew up inside the peritoneal cavity of mice and human KRAS was identified in mucin cfDNA, but not in plasma. All mucins showed the same bacterial profile. Cytokine levels were slightly altered in mice. CONCLUSIONS: The three aPMP patients included in this study shared some common aspects: the absence of tumor cells in mucin, the presence of KRAS mutated cfDNA in mucin, and the absence of this tumor-derived mutation in the bloodstream, providing additional information to the routine pathological examinations and suggesting that mucin cfDNA could potentially play a role in aPMP recurrence and prognosis.

Desarrollo de modelo experimental animal de peritonitis bacteriana / Development of animal experimental model for bacterial peritonitis

OBJETIVO: Desarrollar un modelo de sepsis abdominal en animal de experimentación. MATERIAL Y MÉTODOS: Se utilizan ratas Sprague-Dawley(R), machos de 5 semanas con pesos entre 270-280 g en el momento de la inoculación (N=39). Inicialmente se realiza un estudio piloto (N=9), distribuyéndolas en 3 grupos (3/3/3) con inóculo de 1cc de Escherichia coli ATCC 25922 intraperitoneal en concentraciones de 10E8, 10E9 y 10E10 UFC. En un segundo estudio (N=6) con distribución en dos grupos (3/3) se utilizan 1cc una concentración de E. coli 10E10 UFC que se diluyen en 10 y 15 ml de agua destilada para su inoculación. Por último se inicia un ensayo experimental con aleatorización de 24 ratas en tres grupos de tratamiento tras la infección intraperitoneal: Grupo I con suero fisiológico (N=6), Grupo II con antibiótico (ceftriaxona) (N=9), Grupo III con antibiótico más adyuvante (ceftriaxona más alicina) (N=9). Se realizan muestras microbiológicas de sangre y líquido peritoneal, así como estudio histopatológico de órganos intraperitoneales (hígado, diafragma y peritoneo). RESULTADOS: Se observa muerte en el 100% de las ratas infectadas con la concentración de E. coli 10E10 UFC con la dilución de 15 ml de agua destilada y sin antibiótico. El hemocultivo y cultivo de líquido peritoneal es positivo a la misma cepa en todas ellas. Se observa la formación de abscesos en la superficie del hígado e infiltración por polimorfonucleares en los tejidos. CONCLUSIÓN: Se establece que la dosis letal de E. coli es 10E10 UFC diluida en 15 ml agua destilada en inyección intraperitoneal

OBJECTIVE: The aim of the study was to develop a model of abdominal sepsis in the experimental animal. MATERIAL AND METHODS: Sprague-Dawley male rats of 5 weeks (N=39) were used. Initially, a pilot study (N = 9) was performed and distributed in 3 groups with 1cc inoculum of Escherichia coli ATCC 25922 intraperitoneally at concentrations of 10E8, 10E9 and 10E10 CFU. Subsequently, concentrations of 10E10 CFU are used in two groups of 3 rats with dilutions of 10 cc and 15 cc of distilled water respectively. Finally, a randomized trial of 24 rats was started in three treatment groups after intraperitoneal infection: Group I with physiological serum (N = 6), Group II with ceftriaxone (N = 9), Group III with ceftriaxone plus allicin (N = 9). Microbiological samples of blood and peritoneal fluid were made, as well as histopathological study of intraperitoneal organs (liver, diaphragm and peritoneum). RESULTS: Death of 100% of the rats infected with 10E10 E. coli UFC concentration with the dilution of 15 ml of distilled water and without antibiotic was oberved. The blood culture and peritoneal fluid culture was positive for the same strain in all of them. The formation of abscesses on the liver surface and polymorphonuclear infiltration in tissues were observed. CONCLUSION: The lethal dose of E. coli is 10E10 CFU diluted in 15 cc distilled water by intraperitoneal injection

The Global End-Diastolic Volume (GEDV) Could Be More Appropiate to Fluid Management Than Central Venous Pressure (CVP) During Closed Hyperthermic Intrabdominal Chemotherapy with CO2 Circulation.

BACKGROUND: Closed hyperthermic intraperitoneal chemotherapy (HIPEC) may increase abdominal pressure and effects of hemodynamic changes due to maintenance hyperthermia. Our aim was to analyze the safety and effectiveness of our closed technique with CO2 circulation in management fluid status and hemodynamic parameters by means of cardiac preload control measured by Global End Diastolic Values (GEDV) and a gas exchanger. MATERIAL AND METHODS: A Pilot Clinical Study that included 18 advanced ovarian cancer patients undergoing citoreductive surgery and HIPEC. We used a closed-perfusion system (PRS Combat®) that includes CO2 circulation and a gas exchanger. Transpulmonary thermodilutions and hemodynamic measurements (PiCCO2®) were performed after citoreductive surgery (Pre-HIPEC); At half time of the HIPEC (Intra-HIPEC); After HIPEC (Post-HIPEC). RESULTS: No significant hemodynamic measurements changes in the three thermodilutions values of Cardiac Index (CI) (p = 0.227), Global End Diastolic Values (GEVD) (p = 0.966), Stroke Volume Variation (SVV) (p = 0,884) and Systemic Vascular Resistance Index (SVRI) (p = 0.082). No correlation between central venous pressure (CVP) and GEDV (Pre-HIPEC: r = 0.164, p = 0.211; Intra-HIPEC: r = 0.015, p = 0.900; Post-HIPEC: r = 0.018, p = 0.890). There was better correlation between GEDV and CI (Pre-HIPEC: r = 0.432, p = 0.071; Intra-HIPEC: r = 0.418, p = 0.074; Post-HIPEC: r = 0.411, p = 0.080). CONCLUSIONS: Closed intrabdominal chemotherapy with CO2 circulation model may be a safe model for HIPEC by means of a gas exchanger. GEDV and its changes significantly correlated to CI, and not observed for CVP. GEDV values may be more appropriate for monitoring cardiac preload, blood loss limitation and to predict changes in intravascular volume status during intraperitoneal chemotherapy.

Krukenberg tumor after gastric bypass for morbid obesity. Bariatric surgery and gastric cancer.

Gastric bypass is one of the most frequently performed surgical procedures in bariatric surgery. A neoplasm within the gastric pouch is a somewhat infrequent complication but with important survival consequences. We present the case of a 51-year-old woman who developed an adenocarcinoma in the bypassed stomach three years after bariatric surgery; the tumour was incidentally discovered after gynaecological surgery for uterine myomas. Various diagnostic modalities for the excluded stomach were analysed.

Prognostic implications of serum microRNA-21 in colorectal cancer.

BACKGROUND AND OBJECTIVES: MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in carcinogenesis through postranscriptional gene regulatory activity. Few studies have focused on the detection of miR-21 in serum rather than in tissue. The current study aimed to measure serum miR-21 expression levels and to evaluate their association with the outcome of colorectal cancer (CRC). METHODS: Blood samples were collected from 102 CRC patients undergoing surgery with curative intent. The expression levels of miR-21 were measured using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). The results were analysed to assess the relationship between serum miR-21 levels and patient survival. RESULTS: A univariate analysis revealed that lower expression levels of serum miR-21 were associated with higher local recurrence (P = 0.025) and mortality (P = 0.029). A logistic regression analysis demonstrated that the relative overexpression of miR-21 (expression > 1) was associated with a 51% reduction in the risk of recurrence. A Cox regression analysis identified miR-21 expression as an independent predictor of survival (P = 0.048); a relative increase in miR-21 expression (>1) was associated with a 50% reduction in the risk of mortality. CONCLUSION: The expression level of serum miR-21 correlates with the recurrence and mortality of CRC patients. Our results suggest that circulating serum miR-21 is a promising prognostic tumour marker, and they highlight the potential clinical utility of miR-21 expression as a prognostic marker for CRC prognosis.

Tumor de Krukenberg tras by-pass gástrico por obesidad mórbida. Cirugía bariátrica y cáncer de estómago / Krukenberg tumor after gastric bypass for morbid obesity. Bariatric surgery and gastric cancer

El by-pass gástrico es una de las técnicas quirúrgicas más em - pleadas en la cirugía de la obesidad mórbida. La neoplasia del remanente gástrico es una complicación poco frecuente (se han descrito seis casos a este nivel), pero con consecuencias importantes para la supervivencia de los pacientes. Presentamos el caso de una paciente que desarrolló un adenocarcinoma en el remanente gástrico tres años tras la cirugía bariátrica, descubriéndose como hallazgo casual tras una cirugía ginecológica por miomas uterinos. Se revisan las diferentes modalidades diagnósticas del segmento excluido (AU)

Gastric by-pass is one of the most performed surgical procedure in bariatric surgery. Neoplasm within gastric remnant is a slightly frequent complication (only six cases have been described) but with important survival consequences. We present a case of a patient who developed an adenocarcinoma in excluded stomach, after three years of bariatric surgery; the tumor was incidentally discovered after a gynecological surgery for uterine myomas. Different diagnostic modalities for the excluded stomach were analyzed (AU)

¿Es justificable el reintegro del gasto en enfermos quirúrgicos testigos de Jehová tras asistencia sanitaria ajena al sistema público de salud? / Is the claiming of costs justifiable in Jehovah's witness surgical patients after healthcare that is not part of the public health system?

INTRODUCCIÓN: Los testigos de Jehová rechazan la transfusión sanguínea. El conflicto aparece cuando el enfermo, afiliado a la sanidad pública, acude a centros de cirugía sin sangre, para después reclamar los gastos creados. OBJETIVOS: Análisis de reclamaciones jurídicas de reintegro de gastos en enfermos testigos de Jehová tratados fuera del sistema de salud pública. Comparación de costes, respecto a costes mediante Grupo de Diagnóstico Relacionado (GRD) en un modelo hipotético de asistencia similar e igual estancia en nuestro hospital. MATERIAL Y MÉTODOS: Estudio retrospectivo de sentencias de tribunales Superior de Justicia, Supremo y Constitucional. Análisis económico: utilizamos información clínica obtenida en la sentencia, para procesarlo en GRD, de nuestro hospital con 3MHealth Information Systems. Resultado/conclusiones: El Estado no tiene el deber de financiar aspectos religiosos o ajenos al interés general. El establecimiento de protocolos de actuación evitaría conflictos éticos. Diferencias difícilmente justificables en costes solicitados, 431.001,66 €, y en relación a un modelo con igual estancia, 397.404,48 €

INTRODUCTION: Jehovah's witnesses refuse blood transfusions. The conflict arises when the patient, entitled to public health treatment, come to surgical centres without blood, to later claim the costs incurred. OBJECTIVES: To analyse the legal claims for the refunding of costs by Jehovah's witnesses treated outside the public health system. To make a cost comparison regarding this, using Diagnosis Related Groups (DRGs) in a similar hypothetical healthcare model and equal to a stay in our hospital. MATERIAL AND METHODS: A retrospective study was made of the High, Constitutional, and Supreme Court rulings. A cost analysis was made using the clinical information obtained in the rulings, to process this in the DRG in our hospital using 3MHealth Information Systems. Results/CONCLUSIONS: The State is not obliged to finance religious aspects or those outside the general interest. The establishment of working protocols would avoid ethical conflicts. There are very difficult to justify differences in the costs demanded, 431,001.66 €, and compared to a model with an equal stay, 397,404.48 €

Implications of the histological determination of microRNAs in the screening, diagnosis and prognosis of colorectal cancer.

MicroRNAs are short non-coding RNA molecules that participate in the regulation of gene expression. Several studies have demonstrated the involvement of microRNAs in oncogenesis and a variety of physiological functions. We conducted a literature review of studies that evaluated histological microRNAs in colorectal cancer. Although additional clinical studies are required to substantiate the relationship between microRNAs and colorectal cancer, there is preliminary evidence that microRNAs are related to the diagnosis and prognosis of colorectal cancer.

Diagnostic and prognostic significance of serum microRNAs in colorectal cancer.

MicroRNAs are short non-coding RNA molecules involved in the regulation of gene expression. There are few studies related to the determination of serum microRNAs in colorectal cancer. The identification of microRNAs in peripheral blood as noninvasive markers of tumor disease may lead to potential applications, although further clinical studies focusing on serum microRNAs are required to determine their clinical significance for the diagnosis and prognosis outcome of colorectal cancer.

[Is the claiming of costs justifiable in Jehovah's witness surgical patients after healthcare that is not part of the public health system?]. / ¿Es justificable el reintegro del gasto en enfermos quirúrgicos testigos de Jehová tras asistencia sanitaria ajena al sistema público de salud?

INTRODUCTION: Jehovah's witnesses refuse blood transfusions. The conflict arises when the patient, entitled to public health treatment, come to surgical centres without blood, to later claim the costs incurred. OBJECTIVES: To analyse the legal claims for the refunding of costs by Jehovah's witnesses treated outside the public health system. To make a cost comparison regarding this, using Diagnosis Related Groups (DRGs) in a similar hypothetical healthcare model and equal to a stay in our hospital. MATERIAL AND METHODS: A retrospective study was made of the High, Constitutional, and Supreme Court rulings. A cost analysis was made using the clinical information obtained in the rulings, to process this in the DRG in our hospital using 3MHealth Information Systems. RESULTS/CONCLUSIONS: The State is not obliged to finance religious aspects or those outside the general interest. The establishment of working protocols would avoid ethical conflicts. There are very difficult to justify differences in the costs demanded, 431,001.66 €, and compared to a model with an equal stay, 397,404.48 €.

Epigenética y cáncer colorrectal / Epigenetics and colorectal cancer

Los mecanismos epigenéticos fisiológicos que pueden modificar la estructura de la cromatina comprenden la metilación del ADN, las modificaciones de las histonas y las modificaciones en el RNA. Se ha llevado a cabo una revisión bibliográfica en PubMed acerca de la evidencia publicada sobre la relación existente entre la epigenética y el cáncer colorrectal. La literatura científica pone de manifiesto que en el origen de la enfermedad neoplásica las alteraciones epigenéticas pueden ser tan importantes como las modificaciones genéticas, contribuyendo ambas a la progresión y desarrollo de la enfermedad neoplásica (AU)

The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease (AU)

[Pneumoperitoneum, pneumoretroperitoneum, bilateral pneumothorax, pneumomediastinum and subcutaneous emphysema due ERCP]. / Neumoperitoneo, neumoretroperitoneo, neumotórax bilateral, neumomediastino y enfisema subcutáneo secundario a CPRE.

Endoscopic retrograde cholangiopancreatography (ERCP) has become an essential procedure in the diagnosis and treatment of biliopancreatic diseases. Complications of this procedure are potentially serious, being necessary to know how to recognize them for the application of the appropriate treatment. We report the case of a 79-year-old woman who developed a massive subcutaneous emphysema, bilateral pneumothorax, retropneumomediastinum, retropneumoperitoneum and pneumoperitoneum due to iatrogenic duodenal injury secondary to ERCP. The clinical suspicion for early diagnosis of iatrogenic injury after ERCP will determine the correct treatment of this complication and will achieve better outcomes.

[Epigenetics and colorectal cancer]. / Epigenética y cáncer colorrectal.

The epigenetic and physiological mechanisms that alter the structure of chromatin include the methylation of DNA, changes in the histones, and changes in RNA. A literature review has been carried out using PubMed on the evidence published on the association between epigenetics and colorectal cancer. The scientific literature shows that epigenetic changes, such as genetic modifications may be very significant in the origin of neoplastic disease, contributing both to the development and progression of the disease.

Neumoperitoneo, neumoretroperitoneo, neumotórax bilateral, neumomediastino y enfisema Subcutáneo secundario a CPRE / Pneumoperitoneum neumoretroperitoneo, bilateral pneumothorax, pneumomediastinum and subcutaneous emphysema secondary to ERCP

La colangiografía retrógrada endoscópica (CPRE) se ha convertido en un procedimiento esencial en el diagnóstico y tratamiento de las enfermedades biliopancreáticas. Las complicaciones de este procedimiento son infrecuentes, pero potencialmente graves, siendo necesario saber reconocerlas para la aplicación del tratamiento adecuado. Presentamos el caso clínico de una mujer de 79 años que desarrolló un enfisema subcutáneo, neumotórax bilateral, retroneumomediastino, retroneumoperitoneo y neumoperitoneo debido a una lesión iatrogénica del duodeno secundaria a una colangiografía retrógrada endoscópica. El diagnóstico precoz de las lesiones iatrogénicas tras la realización de una CPRE determinará el correcto tratamiento de esta complicación, que debe comprender variaciones en la clínica y fisiología del paciente.

Endoscopic retrograde cholangiopancreatography (ERCP) has become an essential procedure in the diagnosis and treatment of biliopancreatic diseases. Complications of this procedure are potentially serious, being necessary to know how to recognize them for the application of the appropriate treatment. We report the case of a 79-year-old woman who developed a massive subcutaneous emphysema, bilateral pneumothorax, retropneumomediastinum, retropneumoperitoneum and pneumoperitoneum due to iatrogenic duodenal injury secondary to ERCP. The clinical suspicion for early diagnosis of iatrogenic injury after ERCP will determine the correct treatment of this complication and will achieve better outcomes.

Does bariatric surgery decrease gastric cancer risk?

BACKGROUND/AIMS: In the attempt to establish the different incidence between cancer in anatomically whole stomachs and cancer in patients who have undergone a surgical procedure for morbid obesity, a review on the epidemiology of bariatric surgery and stomach cancer and a correlation with the global incidence of stomach cancer (comparing it with the median age of patients who developed neoplasms after bariatric surgery) have been conducted. METHODOLOGY: This was a descriptive study of the gastric neoplasms located at the gastric pouch, bypassed stomach or in the esophagogastric junction, following bariatric surgery described in the medical literature. RESULTS: Twenty-one cases of gastric neoplasm located at the gastric pouch, in the bypassed stomach or in the esophagogastric junction were described after bariatric surgery. CONCLUSIONS: Bariatric surgery seems to produce a decrease in the incidence of cancer when comparing obese patients who were operated and obese patients who have not, so additional studies are needed to compare the cancer incidence between the general population and patients undergoing bariatric surgery. New studies will determine if it is necessary to focus on the early detection of pathological processes at the excluded digestive tract.