ΔNp73 and its effector targets promote colorectal peritoneal carcinosis and predict survival.

Peritoneal metastasis of colorectal origin appears in ~10-15% of patients at the time of diagnosis and in 30-40% of cases with disease progression. Locoregional spread through the peritoneum is considered stage IVc and is associated with a poor prognosis. The development of a regional therapeutic strategy based on cytoreductive surgery, and hyperthermic intra-abdominal chemotherapy has significantly altered the course of the disease. Although recent evidence supports the benefits of cytoreductive surgery, the benefits of hyperthermic intra-abdominal chemotherapy are, however, still a matter of debate. Understanding the molecular alterations underlying the disease is crucial for developing new therapeutic strategies. Here, we evaluated the involvement in peritoneal dissemination of the oncogenic isoform of TP73, ΔNp73, and its effector targets in in vitro and mouse models, and in 30 patients diagnosed with colorectal peritoneal metastasis. In an orthotopic mouse model, we observed that tumor cells overexpressing ΔNp73 present a higher avidity for the peritoneum and that extracellular vesicles secreted by ΔNp73-upregulating tumor cells enhance their dissemination. In addition, we identified that tumor cells overexpressing ΔNp73 present with dysregulation of genes associated with an epithelial/mesothelial-to-mesenchymal transition (MMT) and that mesothelial cells exposed to the conditioned medium of tumor cells with upregulated ΔNp73 present a mesenchymal phenotype. Lastly, ΔNp73 and its effector target RNAs were dysregulated in our patient series, there were positive correlations between ΔNp73 and its effector targets, and MSN and ITGB4 (ΔNp73 effectors) predicted patient survival. In conclusion, ΔNp73 and its effector targets are involved in the peritoneal dissemination of colorectal cancer and predict patient survival. The promotion of the EMT/MMT and modulation of the adhesion capacity in colorectal cancer cells might be the mechanisms triggered by ΔNp73. Remarkably, ΔNp73 protein is a druggable protein and should be the focus of future studies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. Objective: To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Interventions: Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. Main Outcomes and Measures: The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. Results: A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. Conclusions and Relevance: In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02614534.

Correction to: Training Courses in Laparoscopic Bariatric Surgery on Cadaver Thiel: Results of a Satisfaction Survey on Students and Professors.

The name of author Ramon Vilallonga was misspelled in the original article. It is correct here.

Training Courses in Laparoscopic Bariatric Surgery on Cadaver Thiel: Results of a Satisfaction Survey on Students and Professors.

INTRODUCTION: For the acquisition of skills in laparoscopic surgery, practices in experimental labs are gaining increasing relevance. Activities in experimental labs include Pelvitrainers, virtual reality simulators, and experimental animals (frequently pigs). However, the best model for surgical formation is the performance of interventions on cadavers. The Thiel method gives the body elasticity, which allows the performance of laparoscopic procedures. METHODS: An observational prospective study was performed on surgeons attending to two courses of laparoscopic bariatric surgery on cadavers embalmed by the Thiel method. A questionnaire was given to the participants (students and professors) when finishing the course. Similarities between the procedures performed on cadavers and on patients were investigated. The satisfaction degree was also analyzed. RESULTS: The students recognized that the Thiel cadaver presents elasticity and aspect similar to the patient, and the practice on cadavers is considered the best method for the formation in laparoscopic bariatric surgery. The assistants were extremely satisfied with the acquired skills and considered that these courses should be included in the formation programs for bariatric surgery. The results of the survey on professors agreed with the students in considering the practice on cadavers as the best method for the formation in laparoscopic bariatric surgery. However, they highlighted as drawbacks of the Thiel cadaver, the absence of bleeding, and excessive elasticity of the tissues. CONCLUSION: The participants (students and professors) to the courses of laparoscopic bariatric surgery on cadaver Thiel recognize that these are the most similar model to real conditions in bariatric surgery.

[Splenic lymphangioma. A rare tumour. Presentation of 3 cases and a literature review]. / Linfangioma esplénico. Un tumor raro. Presentación de 3 casos y revisión de la bibliografía.

BACKGROUND: Lymphangiomas are benign tumours, considered to be congenital malformations of the lymphatic system that predominately affect children, with only a few cases reported in adults. The most common sites of these lesions are the neck (75%) and axillary region (20%), but rarely found in the spleen. OBJECTIVE: A description is presented of 3 cases of incidentally detected splenic lymphangioma, one in a child and in 2 adults, respectively, as well as a literature review. CLINICAL CASES: After a clinical and physical examination, all patients had an abdominal ultrasound, CT scan and a complete splenectomy, followed by a histopathological study on the removed spleen. Two patients were asymptomatic, and the paediatric patient referred to intermittent abdominal pain without other symptoms. The clinical and physical examinations related to the mass were negative. The final diagnosis was based on a combination of radiological and histopathological findings. Total splenectomy was undertaken in all cases without complications. CONCLUSIONS: Splenic lymphangioma is very rare, and more so in adults. This condition is often asymptomatic and is incidentally detected by imagenology due to any other differet cause. The final diagnosis should be based on a combination of clinical, radiological, and histopathological findings. Splenectomy is the treatment of choice and the prognosis is good.