A multi-centre randomized controlled trial investigating Consolidation Chemotherapy with and without oxaliplatin in distal rectal cancer and Watch & Wait.

BACKGROUND: Neoadjuvant chemoradiation(nCRT) has been considered the preferred initial treatment strategy for distal rectal cancer. Advantages of this approach include improved local control after radical surgery but also the opportunity for organ preserving strategies (Watch and Wait-WW). Consolidation chemotherapy(cCT) regimens using fluoropyrimidine-based with or without oxalipatin following nCRT have demonstrated to increase complete response and organ preservation rates among these patients. However, the benefit of adding oxaliplatin to cCT compared to fluoropirimidine alone regimens in terms of primary tumor response remains unclear. Since oxalipatin-treatment may be associated with considerable toxicity, it becomes imperative to understand the benefit of its incorporation into standard cCT regimens in terms of primary tumor response. The aim of the present trial is to compare the outcomes of 2 different cCT regimens following nCRT (fluoropyrimidine-alone versus fluoropyrimidine + oxaliplatin) for patients with distal rectal cancer. METHODS: In this multi-centre study, patients with magnetic resonance-defined distal rectal tumors will be randomized on a 1:1 ratio to receive long-course chemoradiation (54 Gy) followed by cCT with fluoropyrimidine alone versus fluoropyrimidine + oxaliplatin. Magnetic resonance(MR) will be analyzed centrally prior to patient inclusion and randomization. mrT2-3N0-1 tumor located no more than 1 cm above the anorectal ring determined by sagittal views on MR will be eligible for the study. Tumor response will be assessed after 12 weeks from radiotherapy(RT) completion. Patients with clinical complete response (clinical, endoscopic and radiological) may be enrolled in an organ-preservation program(WW). The primary endpoint of this trial is decision to organ-preservation surveillance (WW) at 18 weeks from RT completion. Secondary endpoints are 3-year surgery-free survival, TME-free survival, distant metastases-free survival, local regrowth-free survival and colostomy-free survival. DISCUSSION: Long-course nCRT with cCT is associated with improved complete response rates and may be a very attractive alternative to increase the chances for organ-preservation strategies. Fluoropyrimidine-based cCT with or without oxaliplatin has never been investigated in the setting of a randomized trial to compare clinical response rates and the possibility of organ-preservation. The outcomes of this study may significantly impact clinical practice of patients with distal rectal cancer interested in organ-preservation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT05000697; registered on August 11th, 2021.

Implementación segura de la escisión total mesorrectal transanal (TaTME) en la práctica clínica / Safe implementation of total transanal mesorectal excision (TaTME) in clinical practice

Introducción: La escisión total del mesorrecto transanal (TaTME) es una técnica quirúrgica moderna que busca mejorar los resultados oncológicos sorteando dificultades anatómicas y propias del tumor en el cáncer de recto medio e inferior. La expansión de esta operación condujo a complicaciones propias que no se observaban con los procedimientos tradicionales puramente transabdominales. Es por esto que existen recomendaciones de expertos a seguir en el inicio de la práctica del TaTME. Objetivo: Mostrar resultados en la serie inicial de TaTME implementando estrategias de seguridad. Diseño: Análisis retrospectivo sobre una base de datos prospectiva. Métodos: Entre mayo de 2015 y junio de 2018 se seleccionaron pacientes con adenocarcinoma de recto medio o bajo con margen circunferencial de resección respetado sin enfermedad a distancia irresecable. Los pacientes fueron operados con la técnica TaTME por un mismo cirujano "en formación en TaTME" con experiencia y alto volumen de casos de cáncer de recto, habiendo realizado cursos homologados. En algunos de los casos se contó con la asistencia de un especialista internacional "proctor". Resultados: En el período estudiado se operaron 8 pacientes mediante TaTME. Edad media de 62 años (53-77). Siete recibieron Quimiorradioterapia preoperatoria (88%). Todas las piezas tuvieron un margen distal negativo, en 7 de 8 la resección del mesorrecto fue completa y en uno incompleta. El promedio de ganglios resecados fue de 12,5 (6-21). La mediana de tiempo operatorio fue de 351 minutos (255-480). La media de días de internación fue de 10.6 (4-19). Siete pacientes tuvieron complicaciones en el postoperatorio, 4 Clavien I y 3 II. Conclusiones: La aplicación de las estrategias de seguridad durante la implementación de una técnica nueva como el TaTME, ayudaría a la disminución de complicaciones intra y postoperatorias con buenos resultados desde el punto de vista oncológico. (AU)

Introduction: Transanal total mesorectal excision (TaTME) is a modern surgical technique that seeks the best oncological results avoiding anatomic and tumor-specific difficulties in middle and low rectal cancer. The spread of this operation led to complications that were not observed with traditional procedures in a purely transabdominal approach. That is why there are recommendations to follow when starting the TaTME practice. Objective: To show our initial results in TaTME operation implementing security strategies. Design: Retrospective analysis based on a prospective database. Methods: Between May 2015 and June 2018, patients with middle or low rectal adenocarcinoma, with respected circumferential margin in absence of distant unresectable disease were selected. Patients were operated with the TaTME technique by the same surgeon "trainee" with experience and high case volume of rectal cancer, who attended to different courses on the matter. In some of the cases, there was assistance of an international "proctor" specialist. Results: In the period of study, 8 patients underwent surgery through TaTME. Mean age was 62 years (53-77). Seven received preoperative chemoradiotherapy (88%). All the specimens had a negative distal margin, in 7 out of 8, resection of the mesorectum was complete whereas it was incomplete in one. The mean number of resected lymph nodes was 12.5 (6-21). The median operative time was 351 minutes (255-480). The mean time of hospital stay was 10.6 days (4-19). Seven patients had complications in the postoperative period, 4 Clavien I and 3 II. Conclusions: Application of safety strategies during the implementation of a new technique such as TaTME, would help to reduce intra and postoperative complications with good results from the oncological point of view. (AU)

Lateral Node Dissection in Rectal Cancer in the Era of Minimally Invasive Surgery: A Step-by-Step Description for the Surgeon Unacquainted with This Complex Procedure with the Use of the Laparoscopic Approach.

INTRODUCTION: Lateral node dissection in rectal cancer has been routinely performed in Eastern countries. Technical and anatomical challenges and potential significant postoperative morbidity associated with the procedure have prevented its implementation into clinical practice in Western countries. However, the minimally invasive approach may offer the opportunity of performing this complex procedure with precise anatomical dissection and minimal intraoperative blood loss. In this setting, proper training and standardization of technical steps is highly warranted for surgeons not fully acquainted with the procedure. TECHNIQUE: Access to the lateral nodes along the obturator and internal iliac vessels is described by using specific anatomical landmarks. Opening of the peritoneum along the ureter provides access to the region of interest. Dissection of the medial limit is performed preserving the neurovascular bundle and ureter. The lateral dissection is performed along the external iliac vein to provide access to the obturator muscle. Identification of the obturator nerve with blunt dissection of the fat is a critical part of the procedure. Once the lymphatic connections between the inguinal and iliac nodes are transected, dissection is performed along the internal iliac vessels, and branches are separated from the lymphadenectomy specimen. RESULTS: Evidence supports that lateral node dissection performed for highly selected patients with minimally invasive access leads to less intraoperative blood loss and similar oncological outcomes. Technical steps illustrated in the present video may aid surgeons in performing this procedure with precise anatomical landmarks and minimal risk for intraoperative complications. CONCLUSIONS: Lateral node dissection for rectal cancer is a procedure that may follow standardized technical steps by using precise anatomical landmarks with the use of minimally invasive approach.

Is neoadjuvant chemoradiation with dose-escalation and consolidation chemotherapy sufficient to increase surgery-free and distant metastases-free survival in baseline cT3 rectal cancer?

Patients with cT3 rectal cancer are less likely to develop complete response to neoadjuvant chemoradiation (nCRT) and still face significant risk for systemic relapse. In this setting, radiation (RT) dose-escalation and consolidation chemotherapy in "extended" nCRT regimens have been suggested to improve primary tumor response and decrease the risks of systemic recurrences. For these reasons we compared surgery-free and distant-metastases free survival among cT3 patients undergoing standard or extended nCRT. METHODS: Patients with distal and non-metastatic T3 rectal cancer managed by nCRT were retrospectively reviewed. Patients undergoing standard CRT (50.4 Gy and 2 cycles of 5FU-based chemotherapy) were compared to those undergoing extended CRT (54 Gy and 6 cycles of 5FU-based chemotherapy). Patients were assessed for tumor response at 8-10 weeks. Patients with complete clinical response (cCR) underwent organ-preservation strategy (Watch & Wait). Patients were referred to salvage surgery in the event of local recurrence during follow-up. Cox's logistic regression was performed to identify independent features associated with improved surgery-free survival after cCR and distant-metastases-free survival. RESULTS: 155 patients underwent standard and 66 patients extended CRT. Patients undergoing extended CRT were more likely to harbor larger initial tumor size (p = 0.04), baseline nodal metastases (cN+; p < 0.001) and higher tumor location (p = 0.02). Cox-regression analysis revealed that the type of nCRT regimen was not independently associated with distinct surgery-free survival after cCR or distant-metastases-free survival (p > 0.05). CONCLUSIONS: Dose-escalation and consolidation chemotherapy are insufficient to increase long-term surgery-free survival among cT3 rectal cancer patients and provides no advantage in distant metastases-free survival.

Extralevator Abdominal Perineal Excision Versus Standard Abdominal Perineal Excision: Impact on Quality of the Resected Specimen and Postoperative Morbidity.

BACKGROUND: Abdominal perineal excision (APE) has been associated with a high risk of positive circumferential resection margin (CRM+) and local recurrence rates in the treatment of rectal cancer. An alternative extralevator approach (ELAPE) has been suggested to improve the quality of resection by avoiding coning of the specimen decreasing the risk of tumor perforation and CRM+. The aim of this study is to compare the quality of the resected specimen and postoperative complication rates between ELAPE and "standard" APE. METHODS: All patients between 1998 and 2014 undergoing abdominal perineal excision for primary or recurrent rectal cancer at a single Institution were reviewed. Between 1998 and 2008, all patients underwent standard APE. In 2009 ELAPE was introduced at our Institution and all patients requiring APE underwent this alternative procedure (ELAPE). The groups were compared according to pathological characteristics, specimen quality (CRM status, perforation and failure to provide the rectum and anus in a single specimen-fragmentation) and postoperative morbidity. RESULTS: Fifty patients underwent standard APEs, while 22 underwent ELAPE. There were no differences in CRM+ (10.6 vs. 13.6%; p = 0.70) or tumor perforation rates (8 vs. 0%; p = 0.30) between APE and ELAPE. However, ELAPE were less likely to result in a fragmented specimen (42 vs. 4%; p = 0.002). Advanced pT-stage was also a risk factor for specimen fragmentation (p = 0.03). There were no differences in severe (Grade 3/4) postoperative morbidity (13 vs. 10%; p = 0.5). Perineal wound dehiscences were less frequent among ELAPE (52 vs 13%; p < 0.01). Despite short follow-up (median 21 mo.), 2-year local recurrence-free survival was better for patients undergoing ELAPE when compared to APE (87 vs. 49%; p = 0.04). CONCLUSIONS: ELAPE may be safely implemented into routine clinical practice with no increase in postoperative morbidity and considerable improvements in the quality of the resected specimen of patients with low rectal cancers.

Tumor colorrectal de células granulares: presentación de dos casos y revisión de la literatura / Granular cell of colorectal tumor: presentation of two cases and review of the literature

Los tumores de células granulares (Abrikossoff) son tumores estromales benignos que se manifiestan más frecuentemente en la cabeza y cuello. La ubicación colorrectal es menos frecuente. Presentamos 2 casos de ubicación colorrectal. En el primer caso se trató de un tumor ubicado en el recto bajo, a 4 cm del margen anal, que se resecó mediante técnica transanal. El siguiente caso se ubicó en el ciego y, ante la falta de exéresis endoscópica, se resecó mediante hemicolectomía derecha laparoscópica. Ambos tuvieron diagnóstico histopatológico de Tumor de Células Granulares (TCG) confirmado por inmunohistoquímica. Los TCG son tumores generalmente benignos con características inequívocas en el estudio histológico (abundante citoplasma eosinófilo, núcleos pequeños, uniformes y redondos, sin mitosis evidentes) e inmunohistoquímico (PAS y proteína S-100 positivas). Aparecen entre la 4ª y 6ª década en cualquier parte del organismo. En el tubo digestivo aparecen más frecuentemente en el esófago. Debe sospecharse su presencia ante la aparición de un nódulo submucoso sólido, menor de 2 cm, y generalmente único.

Granular cell tumors (Abrikossoff) are benign stromal tumors that usually appear in the head and neck. Colorectal location is less frequent. We present two clinical cases in this location. The first patient presented with a tumor located in the lower rectum, 4 cm from the anal verge, which was resected via local excision. The second case was located in the cecum, and it was resected by laparoscopic right colectomy. Both cases had histopathology diagnosis of Granular cell tumors (GCT) confirmed by immunohistochemistry. GCT are usually benign tumors with unequivocally features in histological analysis (abundant-eosinophilic cytoplasm, small nuclei, round and uniform, without evident mitoses) and immunohistochemichal staining (PAS and S-100 protein positive). The age of presentation is around 4th and 6th decades at any part of the body. In the digestive tract they grow more frequently at the esophagus. Diagnosis should be suspected when facing a unique, solid, less than 2 cm submucosal nodule.

Cáncer anal invasor: análisis de la incidencia en grupos de riesgo en una serie retrospectiva / Invasive anal cancer: analysis of its incidence in high risk group in a retrospective database

Introducción: El cáncer epidermoide de ano incrementó su incidencia de manera exponencial en las últimas décadas. Todos los estudios que investigan la aplicabilidad del papanicolaou anal (PAP) y la anoscopía de alta resolución (AAR) focalizan el estudio en los varones homosexuales con serología VIH positiva. Otros grupos de riesgo son las mujeres con antecedentes de infección genital por HPV y los transplantados e inmunosuprimidos por otras causas. Sin embargo, se observó en nuestra institución una alta proporción de cáncer de ano en pacientes que no encuadraban en estos grupos de riesgo, especialmente mujeres mayores de 60 años. Material y Método: Estudio observacional, retrospectivo, analítico sobre una base de datos y búsqueda en historias clínicas que incluyó a todos los pacientes con diagnóstico de cáncer de ano evaluados en el período marzo de 2001 - marzo de 2011 por el equipo de proctologia del Hospital Ramos Mejia. Se excluyó del análisis a los pacientes con adenocarcinomas de recto, neoplasias cutáneas (melanoma, carcinoma basocelular) y a los que presentaron lesiones anales displásicas (no carcinoma invasor). Resultados: Durante el periodo estudiado se registraron 36 casos con cáncer anal. La edad media de presentación fue de 55,5 años. Se trató de 15 mujeres y 21 hombres (relación mujer/hombre 0,71). Discriminando por edades se trató en 7 casos de menores de 40 años, otros 13 casos de 41-60 años y 16 mayores de 61 años. Dos mujeres entre 10 tenían antecedentes de neoplasias genitales por HPV (1 carcinoma invasor de cérvix y 1 lesión intraepitelial cervical de alto grado) y habían sido tratados con intención curativa. Todos los hombres practicaban el coito anal y 15 individuos presentaban infección por VIH, 13 hombres y 2 mujeres. Ninguno fue transplantado...

Background: Anal squamous cell carcinoma (SCC) rates increased greatly in last decades. There is a connection between HPV viral infection and anal cancer growth, particularly in HIV-infected patients. The majority of papers are advocated to investigate anal pap smear and high-resolution anoscopy in the HIV-infected male who have sex with men group. Other high-risk groups are women with HPV-related disease, organ transplant recipients and immunosuppressed patients. However, we observed a high rate of anal cancer in patients who did not fit for these criteria, especially older women (beyond 60 years old). Patients and Methods: We performed an observational, retrospective study based on a database and medical records. It included all patients evaluated from March 2001 to March 2011 with diagnosis of anal cancer in Hospital J. M. Ramos Mejía. We excluded rectal adenocarcinomas, skin neoplasms and dysplastic anal lesions (non-invasive cancer). Results: During the period of study 36 anal cancers were diagnosed. Median age was 55,5 years. There were 15 women and 21 men (women/men 0,71). Analysis by age showed 7 cases younger than 40 years old, 13 cases between 41-60 years old and finally, 16 cases older than 61 years. Two women in ten had previous diagnosis of gynaecologie HPV-related disease (1 cervical squamous cell cancer and 1 high-grade cervical intraepithelial neoplasia) and had been treated with curative­intention procedures. All men practiced anal intercourse. Fifteen were HIV-infected, 13 men and 2 women. There were no transplant-recipient cases. Discussion: Anal cytology and high-resolution anoscopy were proposed to assess early lesions in high-risk groups (including HIV-infected, MSM, transplant-recipient patients and women with HPV-related disease). We found in our patients a high-rate of anal invasive carcinoma in women older than 60 years old, with no risk-factors associated...

Cáncer anal invasor: análisis de la incidencia en grupos de riesgo en una serie retrospectiva / Invasive anal cancer: analysis of its incidence in high risk group in a retrospective database

Introducción: El cáncer epidermoide de ano incrementó su incidencia de manera exponencial en las últimas décadas. Todos los estudios que investigan la aplicabilidad del papanicolaou anal (PAP) y la anoscopía de alta resolución (AAR) focalizan el estudio en los varones homosexuales con serología VIH positiva. Otros grupos de riesgo son las mujeres con antecedentes de infección genital por HPV y los transplantados e inmunosuprimidos por otras causas. Sin embargo, se observó en nuestra institución una alta proporción de cáncer de ano en pacientes que no encuadraban en estos grupos de riesgo, especialmente mujeres mayores de 60 años. Material y Método: Estudio observacional, retrospectivo, analítico sobre una base de datos y búsqueda en historias clínicas que incluyó a todos los pacientes con diagnóstico de cáncer de ano evaluados en el período marzo de 2001 - marzo de 2011 por el equipo de proctologia del Hospital Ramos Mejia. Se excluyó del análisis a los pacientes con adenocarcinomas de recto, neoplasias cutáneas (melanoma, carcinoma basocelular) y a los que presentaron lesiones anales displásicas (no carcinoma invasor). Resultados: Durante el periodo estudiado se registraron 36 casos con cáncer anal. La edad media de presentación fue de 55,5 años. Se trató de 15 mujeres y 21 hombres (relación mujer/hombre 0,71). Discriminando por edades se trató en 7 casos de menores de 40 años, otros 13 casos de 41-60 años y 16 mayores de 61 años. Dos mujeres entre 10 tenían antecedentes de neoplasias genitales por HPV (1 carcinoma invasor de cérvix y 1 lesión intraepitelial cervical de alto grado) y habían sido tratados con intención curativa. Todos los hombres practicaban el coito anal y 15 individuos presentaban infección por VIH, 13 hombres y 2 mujeres. Ninguno fue transplantado...(AU)

Background: Anal squamous cell carcinoma (SCC) rates increased greatly in last decades. There is a connection between HPV viral infection and anal cancer growth, particularly in HIV-infected patients. The majority of papers are advocated to investigate anal pap smear and high-resolution anoscopy in the HIV-infected male who have sex with men group. Other high-risk groups are women with HPV-related disease, organ transplant recipients and immunosuppressed patients. However, we observed a high rate of anal cancer in patients who did not fit for these criteria, especially older women (beyond 60 years old). Patients and Methods: We performed an observational, retrospective study based on a database and medical records. It included all patients evaluated from March 2001 to March 2011 with diagnosis of anal cancer in Hospital J. M. Ramos Mejía. We excluded rectal adenocarcinomas, skin neoplasms and dysplastic anal lesions (non-invasive cancer). Results: During the period of study 36 anal cancers were diagnosed. Median age was 55,5 years. There were 15 women and 21 men (women/men 0,71). Analysis by age showed 7 cases younger than 40 years old, 13 cases between 41-60 years old and finally, 16 cases older than 61 years. Two women in ten had previous diagnosis of gynaecologie HPV-related disease (1 cervical squamous cell cancer and 1 high-grade cervical intraepithelial neoplasia) and had been treated with curative¡intention procedures. All men practiced anal intercourse. Fifteen were HIV-infected, 13 men and 2 women. There were no transplant-recipient cases. Discussion: Anal cytology and high-resolution anoscopy were proposed to assess early lesions in high-risk groups (including HIV-infected, MSM, transplant-recipient patients and women with HPV-related disease). We found in our patients a high-rate of anal invasive carcinoma in women older than 60 years old, with no risk-factors associated...(AU)

Carcinomatosis peritoneal de origen colorrectal. Cirugía citorreductora y quimioterapia hipertérmica intraperitoneal / Colorectal peritoneal carcinomatosis: citoreductive surgery and hyperthermic intraperitoneal chemotherapy

Antecedentes: El pronóstico de los pacientes con carcinomatosis peritoneal de origen colorrectal es pobre. Tradicionalmente, para su tratamiento se utilizó la quimioterapia sistémica mientras que la cirugía estuvo reservada al tratamiento de las complicaciones. Objetivo: Establecer el estado actual de la cirugía citorreductora y la quimioterapia hipertérmica y valorar sus alcances en parámetros objetivos de acuerdo con la bibliografía. Material y Métodos: Se utilizaron para la búsqueda todos los artículos publicados acerca del tema en inglés y francés entre los años 1990 y 2008 en las bases de datos de PubMed de la Biblioteca Nacional de Medicina de los EEUU. Resultados: La cirugía citorreductora actúa sobre las masas neoplásicas macroscópicas, mientras que la quimioterapia hipertérmica intraperitoneal (QTHIP) es útil para tratar la enfermedad residual microscópica. La asociación entre ambas se debe a que la primera intenta resecar todo el tumor visible o, en su defecto, hasta 2 mm de espesor, a fin de permitir la acción de las drogas quimioterápicas, que pueden penetrar esa distancia como máximo en los tejidos tumorales. Los pacientes con un aceptable estado clínico (“performance status”), sin diseminación extraabdominal, con metástasis ganglionares y/o hepáticas resecables, baja carga de enfermedad peritoneal y potencialmente pasibles de una citorreducción completa, se considerarían para este tratamiento combinado. Los factores predictivos más utilizados en la actualidad lo constituyen el Índice de Cáncer Peritoneal (ICP) y la Citorreducción Completa. La mayoría de los autores coincide en admitir que los beneficios de la cirugía citorreductora (CC) más la QTHIP dependen principalmente de la capacidad de la cirugía de alcanzar una resección completa. La quimioterapia intraperitoneal no ha podido, por sí sola, tratar grandes volúmenes de carcinomatosis: solamente se han reportado tratamientos exitosos con el tratamiento combinado...

Background: Colorectal peritoneal carcinomatosis leads to a poor prognosis. Traditionally, its treatment has consisted in systemic chemotherapy, whereas surgery has been reserved to the management of complications. Objective: To establish the current state of cytoreductive surgery (CRS) and hyperthermic chemotherapy (HIPEC), and to assess their implications with objective parameters according to literature. Material and Methods: All papers published in english and french about the subject between 1990 and 2008 in the PubMed database were retrieved. Results: Cytoreductive surgery works over macroscopic neoplastic masses, as on microscopic residual disease HIPEC does. Their association is realted with their goals: the first one tries to resect all visible tumor or at least less than 2 mm, to allow chemoterapic drugs a deep penetration in tumoral tissues. Patients with an adequate performance status, with no extraabdominal spread, with resectable lymph nodes and/or hepatic metastasis, low burden of peritoneal disease and potentially fit for a complete cytoreduction, would be considered for this treatment. Nowadays, the most utilized predictive factors are constituted by the Peritoneal Cancer Index and Completeness of Cytoreduction. Most authors agree in the consideration that CRS plus HIPEC benefits depends mainly on the possibility of a complete surgical resection. Intraperitoneal chemotherapy could not, for its own, treat large tumoral masses: there are only reported successful treatments with the combined modality. At the same time, most papers prove that HIPEC combined with an optimum cytoreductive surgery cures about 25 per cent of the patients considered as unresectable. Benefits in survival related to this treatment are reached in spite of a high morbidity and mortality. The most severe complications are represented by anastomotic fistulas...