Undetectable circulating tumor DNA confirms the inability of pseudomyxoma peritonei to systemic dissemination.

The study of circulating tumor DNA (ctDNA) plays a pivotal role in advancing precision oncology, providing valuable information for individualized patient care and contributing to the ongoing effort to improve cancer diagnosis, treatment, and management. However, its applicability in pseudomyxoma peritonei (PMP) remains unexplored. In this multicenter retrospective study involving 21 PMP patients, we investigated ctDNA presence in peripheral blood using three distinct methodologies. Despite mucinous tumor tissues exhibiting KRAS and GNAS mutations, ctDNA for these mutations was undetectable in blood samples. In this pilot study, circulating tumor DNA was not detected in blood when the tumor harbored mutations of known significance. In the future, a study with a larger sample size is needed to confirm these findings and to determine whether ctDNA could identify patients at risk for early recurrence and/or systemic metastases.

Therapeutic effect of adipose-derived mesenchymal stem cells in a porcine model of abdominal sepsis.

BACKGROUND: The term sepsis refers to a complex and heterogeneous syndrome. Although great progress has been made in improving the diagnosis and treatment of this condition, it continues to have a huge impact on morbidity and mortality worldwide. Mesenchymal stem cells are a population of multipotent cells that have immunomodulatory properties, anti-apoptotic effects, and antimicrobial activity. We studied these capacities in a porcine model of peritoneal sepsis. METHODS: We infused human adipose-derived mesenchymal stem cells (ADSCs) into a porcine model of peritoneal sepsis. Twenty piglets were treated with antibiotics alone (control group) or antibiotics plus peritoneal infusion of ADSCs at a concentration of 2 × 106 cells/kg or 4 × 106 cells/kg (low- and high-dose experimental groups, respectively). The animals were evaluated at different time points to determine their clinical status, biochemical and hematologic parameters, presence of inflammatory cytokines and chemokines in blood and peritoneal fluid, and finally by histologic analysis of the organs of the peritoneal cavity. RESULTS: One day after sepsis induction, all animals presented peritonitis with bacterial infection as well as elevated C-reactive protein, haptoglobin, IL-1Ra, IL-6, and IL-1b. Xenogeneic ADSC infusion did not elicit an immune response, and peritoneal administration of the treatment was safe and feasible. One day after infusion, the two experimental groups showed a superior physical condition (e.g., mobility, feeding) and a significant increase of IL-10 and TGF-ß in blood and a decrease of IL-1Ra, IL-1b, and IL-6. After 7 days, all animals treated with ADSCs had better results concerning blood biomarkers, and histopathological analysis revealed a lower degree of inflammatory cell infiltration of the organs of the peritoneal cavity. CONCLUSIONS: Intraperitoneal administration of ADSCs as an adjuvant therapy for sepsis improves the outcome and diminishes the effects of peritonitis and associated organ damage by regulating the immune system and reducing intra-abdominal adhesions in a clinically relevant porcine model of abdominal sepsis.

Extended totally extraperitoneal (eTEP) treatment for lateral primary and incisional hernias. New approach to old problems.

PURPOSE: To describe the eTEP approach for treating lateral primary and incisional hernia and show its results in a prospective series of cases. METHODS: A descriptive prospective study with patients treated surgically for lateral hernias using eTEP approach. Every patient was operated by the same surgeon from November 2018 to December 2021. Inclusion criteria were primary and incisional hernia, lateral and W1 and W2 sized using the EHS classification. Exclusion criteria were W3 hernia, loss of domain, need to remove previous mesh, dystrophic or ulcerative skin, history of previous complex surgery. Details of the surgical technique are described. RESULTS: 34 patients were operated. Median age was 65 years old and BMI, 29.9 (22.1-47.1). There were several locations being the most frequent L3 in 18 patients. The median length was 41 mm (10-129) and width, 44 mm (10-97). The median of defect-mesh ratio was 5.05 (0.9-447.64). TAR was practised in 21 patients (61.8%). Only one patient suffered a clinically relevant complication, being a hematoma (Dindo-Clavien II). 50% of patients were operated in ambulatory surgery. After a median follow-up of 13.5 months, only one recurrence has been reported (2.9%). CONCLUSION: eTEP to treat lateral hernias is feasible and reproducible showing good results in terms of hernia recurrence and complications. A further prospective randomized clinical trial is needed to support these results.

Toxicity study in a pig model of intraperitoneal collagenase as an "enzymatic scalpel" directed to break stroma in order to generate a new perspective for peritoneal carcinomatosis approach: an experimental research.

BACKGROUND: This study aimed to measure the toxicity resulting from collagenase administration to the peritoneal cavity in a pig model as a preliminary step to break down the stroma surrounding tumors. METHODS: Eight pigs were treated with 2 different collagenase concentrations previously tested in rats by our group. Time and temperature were controlled using a peritoneal lavage system (PRS System, Combat Medical Ltd.) identical to that used in human surgeries through hyperthermic intraperitoneal chemotherapy (HIPEC); 2 additional pigs were treated with peritoneal lavage only. Samples of blood and peritoneal fluid were collected pre-treatment, immediately after treatment, and 24 h postoperatively. In addition, histological studies and blood collagenase levels were measured. RESULTS: No complications were observed during the surgeries. Intraoperative images evidenced the release of peritoneal tissue during collagenase treatment. After surgery, the animals showed no signs of pain. Diet and mobility were normal at 4 h postoperatively, and there were no significant differences in hematologic or biochemical parameters. Quantification of MMP1 and MMP2 in all samples as measured by absorbance showed no differences in blood collagenase levels between pre-treatment, post-treatment, and 24 h postoperatively. None of the animals treated with collagenase showed peritoneal adhesions during the second surgery. Histologically, peritoneal organs and serous structures did not show any microscopic alterations associated with collagenase treatment in any group. CONCLUSION: Lavage of the peritoneal cavity with doses of up to 100,000 collagen digestion units/animal for 30 min is safe and removes connective tissue from the peritoneal cavity.

Intraperitoneal collagenase as a novel therapeutic approach in an experimental model of colorectal peritoneal carcinomatosis.

The usefulness of local collagenase in therapeutic approaches to solid tumors has been tested recently. In this study, we evaluate the safety and efficacy of intraperitoneal collagenase associated or not to mitomycin for treatment of colorectal peritoneal metastases in an experimental rat model. Using a fixed-dose procedure, we found that a dose of collagenase of 37 IU/mL administered for 15 min with a hyperthermia pump at 37.5 °C, both in isolation or associated to sequential treatment with intraperitoneal mitomycin, led to a macroscopic decrease in tumor volume as evaluated by the modified peritoneal cancer index (mPCI). Concerning the safety of the procedure, the animals showed no physiological or behavioral disorders during 8 weeks of follow-up. Local treatment for peritoneal metastases of colorectal origin with intraperitoneal collagenase has proved safe and effective in an experimental murine model. Therefore, the stroma-first approach by enzymatic breakdown of collagen from the tumor's extracellular matrix provides a new therapeutic target for colorectal peritoneal metastases.

Complete laparoscopic pelvic peritonectomy plus hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of our study was to present the technique for, and early results of complete laparoscopic pelvic peritonectomy (LPP) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a study on consecutive patients who had LPP for limited peritoneal carcinomatosis (peritoneal carcinomatosis index < 10) from ovarian cancer, colon cancer and benign multicystic mesothelioma, from January 2017 to November 2019 at 2 referral centers in Spain. Perioperative, pathologic, 30-day major morbidity and mortality characteristics were analyzed. The surgical technique is shown in the attached video. RESULTS: Twelve LPP + HIPEC were performed. Complete cytoreduction was achieved in 100% of the patients, the median duration of the operation was 450 min (range 360-600 min). There were 2 cases (16%) of IIIa morbidity (trocar hernia and pleural effusion), and no mortality. The median length of hospital stay was 5.5 days (range 4-10 days). The median length of follow-up was 10 months (range 2-30 months). There was a recurrence at the splenic hilum in 1 patient which was treated by laparoscopic splenectomy and one nodal recurrence at 13 months while all other patients are alive and free of disease at last follow-up. CONCLUSIONS: This is the first technical video of a minimally invasive approach for complete pelvic peritonectomy plus omentectomy associated with HIPEC. For highly selected patients, this procedure presents a feasible and safe alternative to the maximally invasive approach.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

Serum VEGF and VEGF-C values before surgery and after postoperative treatment in gastric cancer

INTRODUCTION: Angiogenesis and lymphangiogenesis are essential processes for the formation of blood and lymphatic vessels that allow tumour growth and spread. The binding of VEGF and VEGF-C factors with their receptors (VEGFR2, VEGFR3) in endothelial cells triggers signals that regulate these processes. We compared preoperative serum VEGF and VEGF-C levels with samples obtained after completion of surgery and adjuvant treatment in patients with gastric cancer. In addition, we determined the prognostic value and relationship to survival of serum VEGF and VEGF-C levels. METHODS: We used a prospective cohort study of 59 gastric cancer patients who underwent surgery. Serum VEGF and VEGF-C were measured by enzyme-linked immunosorbent assay (ELISA) the day before surgery and 6 months later, after completion of adjuvant treatment. RESULTS: Serum VEGF values decreased after treatment in patients with resectable tumours (mean ± SD) (405.42 ± 298.38 vs. 306.38 ± 212.47 pg/ml; p < 0.01), poorly differentiated and undifferentiated tumours (G3, G4) (438 ± 339.71 vs. 322.47 ± 210.71 pg/ml; p = 0.01), locally advanced gastric tumours (T4 stage) (424.27 ± 323.08 vs. 333.62 ± 221.72 pg/ml; p = 0.03) and tumours with a greater number of involved regional lymph nodes (N3) (442.38 ± 311.52 vs. 337.4 ± 203.64 pg/ml; p = 0.04). Serum preoperative VEGF values over 761 pg/ml were associated with shorter patient survival. The mean overall survival time for patients with serum VEGF levels higher than 761 pg/ml was 7 ± 2.99 months (95 % CI 1.14-12.86) while for patients with serum VEGF levels of less than 761 pg/ml was 21.18 ± 2.88 (95 % CI 15.54-26.83) The mean disease-specific survival time for patients with serum VEGF levels higher than 761 pg/ml was 6.25 ± 2.53 months (95 % CI 1.29-11.21) while for patients with serum VEGF levels of less than 761 pg/ml was 27.57 ± 3.45 (95 % CI 20.80-34.35). Multivariate analysis identified preoperative serum VEGF levels as an independent prognostic factor (HR = 0.144; p = 0.03). CONCLUSIONS: Serum VEGF levels decreased after the completion of treatment in patients with resected tumours, suggesting VEGF tracking may be useful in monitoring progression. Preoperative measurement of serum VEGF may help us identify patients with a poor prognosis (AU)

Implicaciones clínicas de la determinación histológica de los micrornas en el cáncer colorrectal / Clinical implication of histological determination of micrornas in colorectal cancer

Los microRNAs son estructuras moleculares con actividad post-transcripcional que están implicados en la regulación de la expresión genética. Diversos estudios ponen de manifiesto la participación de los microRNAs con distintas funciones fisiológicas, así como con el proceso de la oncogénesis. La expresión de los microRNAs puede verse alterada en las neoplasias por su interacción bien con los genes supresores de tumores, bien con los oncogenes. Se ha llevado a cabo una revisión bibliográfica en PubMed acerca de la evidencia publicada sobre la determinación histológica de los microRNAs y la relación existente con el diagnóstico y el pronóstico del cáncer colorrectal. A pesar de ser preciso nuevos estudios clínicos que especifiquen la relación de los microRNAs con el cáncer colorrectal, se ha evidenciado una relación de estas estructuras con el diagnóstico y pronóstico de esta neoplasia (AU)

MicroRNAs are short non-coding RNA molecules involved in the regulation of gene expression. Several studies demonstrate the involvement of microRNAs with different physiological functions and oncogenesis. The expression of microRNAs may be altered in tumors by their interaction with tumor suppressor genes or with oncogenes. A literature review in PubMed was made about the evidence on the histological determination of microRNAs and the relationship with the diagnosis and prognosis of colorectal cancer. Although further clinical studies focusing on serum microRNAs are required to determine the relationship of microRNAs in colorectal cancer, the relationship of these structures with the diagnosis and prognosis of this neoplasm has been shown (AU)

Microrna-21 y cáncer colorrectal / Microrna - 21 and colorectal cancer

Introducción. Los microRNAs son estructuras moleculares con actividad post-transcripcional que están implicados en la regulación de la expresión genética. Diversos estudios ponen de manifiesto la participación de los microRNAs con distintas funciones fisiológicas, así como con el proceso de la oncogénesis. La expresión de los microRNAs puede verse alterada en las neoplasias por su interacción bien con los genes supresores de tumores, bien con los oncogenes. Discusión. Llevamos a cabo una revisión de la literatura sobre el microRNA-21, poniendo de manifiesto la evidencia existenteentre el microRNA-21 y la enfermedad neoplásica, de forma especial con el cáncer colorrectal. Conclusiones. El estado actual de los microRNAs hace necesario continuar con la investigación existente entre la etiopatogenia de las neoplasias y los microRNAs. El conocimiento de la verdadera implicación de los microRNAs en la fisiopatología de la enfermedad neoplásica, permitirá ampliar las supuestas aplicaciones clínicas del miR-21 no sólo a la determinación del pronóstico del cáncer colorrectal, sino también desde el punto de vista diagnóstico al poder diferenciar las lesiones de la mucosa colónica (AU)

Introduction. MicroRNAs are molecular structures with post-transcriptional activity, involved in the gene expression regulation. Several studies have demonstrated the involvement of microRNAs in different physiological functions, as well as in the oncogenesis process. The expression of microRNAs may be altered in the tumors by either interaction with tumor suppressor genes or oncogenes. Discussion. A review of the medical literature on microRNA-21 has been conducted, showing the evidence between microRNA-21 and neoplastic disease, specially with colorectal cancer. Conclusion. The current status of microRNAs makes necessary to continue the investigation of the pathogenesis of cancer and microRNAs. The knowledge of the involvement of microRNAs in the pathophysiology of neoplastic disease, will allow to extend the supposed clinical applications of miR-21 not only to the determination of the prognosis of colorectal cancer, but also for the differential diagnosis of processes of colonic mucosae (AU)

Investigación en la Unidad de Cirugía Mayor Ambulatoria / No disponible

Fundamento: El concepto de la Cirugía Mayor Ambulatoria(CMA) presenta fundamentalmente un enfoque terapéutico, existiendo la posibilidad en el contexto de este modelo asistencial de efectuar procesos de investigación. El objetivo que se pretende es analizar la utilización de la unidad de CMA como modelo referencial para la realización de estudios clínicos, por lo que se presenta una revisión descriptiva de las comunicaciones más recientes a los congresos de Cirugía Mayor Ambulatoria. Métodos: Estudio descriptivo de las comunicaciones a las Reuniones Nacionales e Internacionales durante los años 2007 y2008, contabilizándose las comunicaciones orales y de tipo póster que describían un estudio prospectivo o retrospectivo. Resultados: Se revisaron las comunicaciones pertenecientes al 7th International Congress of Ambulatory Surgery (IAAS), VII Congreso Nacional de Cirugía Mayor Ambulatoria y VII Simposio de la Asociación Española de Cirugía Mayor Ambulatoria. Se revisaron un total de 503 comunicaciones deslindadas en: 51 estudios prospectivos (10,12%) y 57 estudios retrospectivos (11,33%).Conclusiones: Aun cuando la realización de procesos de investigación resulta perfectamente compatible con determinados modelos organizativos asistenciales como la CMA, se constata una marcada infrautilización de este tipo de organización sanitaria en relación con las actividades investigadoras (AU)

Background: The Ambulatory Surgical Unit has an essentially therapeutic approach, although it is possible, within this organizational model, to develop investigation procedures. The purpose of this study is to analyze the use of the ambulatory surgical unit for the development of clinical studies, so we undertook a descriptive study of the papers sent to the most recent congresses on ambulatory surgery.Methods: A descriptive study of the papers sent to the national and international meetings of 2007-2008, including oral communications and posters describing a prospective or retrospective study. Results: We checked the communications sent to the IAAS7th International Congress of Ambulatory Surgery, VII Congreso Nacional de Cirugía Mayor Ambulatoria and VII Simposio de la Asociación Española de Cirugía Mayor Ambulatoria. Were viewed 503 communications, of which 51 were prospective studies (10.12%) and 57 retrospective studies (11.33%).Conclusions: Although investigation studies are perfectly compatible with certain organizational models of care such as the ambulatory surgical unit, there is a marked under-utilization of this type of health organization in connection with investigation activitie (AU)

Marjolin's ulcer arising from a laparostomy scar.

Marjolin's ulcer is the malignant transformation of a scar, usually as a squamous cell carcinoma. An uncommon presentation form is from a laparostomy scar. A 49-year-old patient that had a laparostomy during the treatment of a necrohemorrhagic pancreatitis in 1987 complained 13 years later of a 20-cm ulcer on the laparostomy scar. A resection of the abdominal wall including the ulcer and a segmental transverse colectomy were performed because of infiltration by an invasive squamous cell carcinoma. Ten months later, axillary lymphadenectomy was performed because of lymph node metastasis. Currently, the patient is free of disease. Lymph node infiltration is frequent in squamous cell carcinoma on Marjolin's ulcer and survival is not good. Prophylaxis of this disease includes meticulous care of wounds, with early skin grafts when required and treatment of infections.