Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer.

BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts. Similarly, the more invasive VilCre ERT2 Apc fl/+ Pten fl/+ mouse model showed an overexpression of eNOS in intestinal tumors whereas this isoform was not expressed in normal tissue. However, none of the three models showed iNOS expression. Notably, when 40 human colorectal tumors were classified into different clinically relevant molecular subtypes, high eNOS expression was found in the poor relapse-free and overall survival mesenchymal subtype, whereas iNOS was absent. Furthermore, Apc fl/fl organoids overexpressed eNOS compared with wild-type organoids and NO depletion with the scavenger carboxy-PTIO (c-PTIO) decreased the proliferation and the expression of stem-cell markers, such as Lgr5, Troy, Vav3, and Slc14a1, in these intestinal organoids. Moreover, specific NO depletion also decreased the expression of CSC-related proteins in human colorectal cancer cells such as ß-catenin and Bmi1, impairing the CSC phenotype. To rule out the contribution of iNOS in this effect, we established an iNOS-knockdown colorectal cancer cell line. NO-depleted cells showed a decreased capacity to form tumors and c-PTIO treatment in vivo showed an antitumoral effect in a xenograft mouse model. CONCLUSION: Our data support that eNOS upregulation occurs after Apc loss, emerging as an unexpected potential new target in poor-prognosis mesenchymal colorectal tumors, where NO scavenging could represent an interesting therapeutic alternative to targeting the CSC subpopulation.

Respuesta al tratamiento e intervalo de tiempo hasta la cirugía con radioterapia preoperatoria de curso corto en el cáncer de recto / Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer

INTRODUCCIÓN: La radioterapia preoperatoria de curso corto con cirugía inmediata, mejora el control local del cáncer rectal. Las respuestas que consigue son de menor magnitud que las descritas con radioquimioterapia. Datos preliminares asocian esta menor respuesta al corto periodo hasta la cirugía. El objetivo de este estudio es analizar la respuesta obtenida con el esquema preoperatorio de curso corto y su correlación con el tiempo hasta la cirugía, analizando especialmente a los pacientes con fascia mesorrectal afectada. MÉTODOS: Se analiza retrospectivamente a 155 pacientes tratados con radioterapia preoperatoria (5×5Gy). Se cuantificó la respuesta tumoral en términos de tasas de respuesta completa patológica, reducción del estadio, grado de regresión tumoral y estado del margen de resección circunferencial. RESULTADOS: El intervalo medio radioterapia-cirugía fue de 23 días. Se alcanzaron respuestas completas patológicas en el 2,2% y reducción del estadio en el 28%. No se detectaron diferencias entre estas tasas y el intervalo hasta la cirugía. Ochenta y ocho pacientes tenían resonancia de estadificación (31 con fascia mesorrectal comprometida). La media de tiempo hasta la intervención en pacientes con fascia comprometida y cirugía R0 fue de 27 días y si R1 de 16 días (p = 0,016). El punto de corte de 20 días alcanzó la mayor probabilidad de lograr un margen circunferencial negativo entre los pacientes con fascia mesorrectal comprometida, aunque sin alcanzar significación estadística: RR 3,036, IC del 95%=0,691-13,328, p = 0,06. CONCLUSIONES: Tras la radioterapia preoperatoria de curso corto, un intervalo > 20 días potencia la probabilidad de lograr un margen de resección libre en pacientes con fascia mesorrectal comprometida

INTRODUCTION: Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. METHODS: A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. RESULTS: The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P = .016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI = (0.691-13.328),P = .06. CONCLUSIONS: After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement

Response to treatment and interval to surgery after preoperative short-course radiotherapy in rectal cancer. / Respuesta al tratamiento e intervalo de tiempo hasta la cirugía con radioterapia preoperatoria de curso corto en el cáncer de recto.

INTRODUCTION: Preoperative short-course radiotherapy with immediate surgery improves local control in patients with rectal cancer. Tumor responses are smaller than those described with radiochemotherapy. Preliminary data associate this lower response to the short period until surgery. The aim of this study is to analyze the response to preoperative short-course radiotherapy and its correlation with the interval to surgery especially analyzing patients with mesorectal fascia involvement. METHODS: A total of 155 patients with locally advanced rectal cancer treated with preoperative radiotherapy (5×5Gy) were retrospectively analyzed. Tumor response in terms of rates of complete pathological response, downstaging, tumor regression grading and status of the circumferential resection margin were quantified. RESULTS: The mean interval from radiotherapy to surgery was 23 days. The rate of complete pathological response was 2.2% and 28% experienced downstaging (stage decreased). No differences between these rates and interval to surgery were detected. Eighty-eight patients had magnetic resonance imaging for staging (in 31 patients the mesorectal fascia was involved).The mean time to surgery in patients with involvement of the fascia and R0 surgery was 27 days and 16 days if R1 (P=.016). The cutoff of 20 days reached the highest probability of achieving a free circumferential resection margin between patients with mesorectal fascia involvement, with no statistically significant differences: RR 3.036 95% CI=(0.691-13.328), P=.06. CONCLUSIONS: After preoperative short-course radiotherapy, an interval>20 days enhances the likelihood of achieving a free circumferential resection margin in patients with mesorectal fascia involvement.

New trends in the management of diverticulitis and colonic diverticular disease.

Colonic diverticular disease is a chronic disorder presenting with a variety of abdominal symptoms and recurrent episodes of acute diverticulitis. It is close linked to age so its prevalence has risen notably during the last decades in western countries, increasing costs related to medical attention. Recently, several works have provided evidence to a series of measures that could improve the outcomes as well as reduce expenses associated to this process.The aim of the present review is to expose a view of the new trends in the management of diverticulitis and colonic diverticular disease, based on the highest clinical evidence available.

Nuevas tendencias en el manejo de la diverticulitis y la enfermedad diverticular del colon / New trends in the management of diverticulitis and colonic diverticular disease

La enfermedad diverticular del colon es una entidad crónica con una variada sintomatología abdominal que puede cursar con episodios recurrentes de diverticulitis aguda. Debido a su estrecha relación con la edad, su prevalencia ha aumentado de forma muy significativa en los países de occidente en las últimas décadas, incrementando sobremanera los gastos derivados de su tratamiento. Recientemente, varios trabajos han aportado evidencia a una serie de medidas que podrían mejorar los resultados al tiempo que disminuir los gastos asociados a este proceso. El objetivo de la presente revisión es exponer una visión, basada en la mayor evidencia disponible, de las nuevas tendencias en el manejo de la diverticulitis aguda y enfermedad diverticular del colon

Colonic diverticular disease is a chronic disorder presenting with a variety of abdominal symptoms and recurrent episodes of acute diverticulitis. It is close linked to age so its prevalence has risen notably during the last decades in western countries, increasing costs related to medical attention. Recently, several works have provided evidence to a series of measures that could improve the outcomes as well as reduce expenses associated to this process. The aim of the present review is to expose a view of the new trends in the management of diverticulitis and colonic diverticular disease, based on the highest clinical evidence available