Time Interval Between the End of Neoadjuvant Therapy and Elective Resection of Locally Advanced Rectal Cancer in the CRONOS Study.

Importance: The treatment for extraperitoneal locally advanced rectal cancer (LARC) is neoadjuvant therapy (NAT) followed by total mesorectal excision (TME). Robust evidence on the optimal time interval between NAT completion and surgery is lacking. Objective: To assess the association of time interval between NAT completion and TME with short- and long-term outcomes. It was hypothesized that longer intervals increase the pathologic complete response (pCR) rate without increasing perioperative morbidity. Design, Setting, and Participants: This cohort study included patients with LARC from 6 referral centers who completed NAT and underwent TME between January 2005 and December 2020. The cohort was divided into 3 groups depending on the time interval between NAT completion and surgery: short (≤8 weeks), intermediate (>8 and ≤12 weeks), and long (>12 weeks). The median follow-up duration was 33 months. Data analyses were conducted from May 1, 2021, to May 31, 2022. The inverse probability of treatment weighting method was used to homogenize the analysis groups. Exposure: Long-course chemoradiotherapy or short-course radiotherapy with delayed surgery. Main outcome and Measures: The primary outcome was pCR. Other histopathologic results, perioperative events, and survival outcomes constituted the secondary outcomes. Results: Among the 1506 patients, 908 were male (60.3%), and the median (IQR) age was 68.8 (59.4-76.5) years. The short-, intermediate-, and long-interval groups included 511 patients (33.9%), 797 patients (52.9%), and 198 patients (13.1%), respectively. The overall pCR was 17.2% (259 of 1506 patients; 95% CI, 15.4%-19.2%). When compared with the intermediate-interval group, no association was observed between time intervals and pCR in short-interval (odds ratio [OR], 0.74; 95% CI, 0.55-1.01) and long-interval (OR, 1.07; 95% CI, 0.73-1.61) groups. The long-interval group was significantly associated with lower risk of bad response (tumor regression grade [TRG] 2-3; OR, 0.47; 95% CI, 0.24-0.91), systemic recurrence (hazard ratio, 0.59; 95% CI, 0.36-0.96), higher conversion risk (OR, 3.14; 95% CI, 1.62-6.07), minor postoperative complications (OR, 1.43; 95% CI, 1.04-1.97), and incomplete mesorectum (OR, 1.89; 95% CI, 1.02-3.50) when compared with the intermediate-interval group. Conclusions and Relevance: Time intervals longer than 12 weeks were associated with improved TRG and systemic recurrence but may increase surgical complexity and minor morbidity.

Functional Outcomes and Quality of Life After Transanal Total Mesorectal Excision for Rectal Cancer: A Prospective Observational Study.

BACKGROUND: Few studies have addressed the functional impact after transanal total mesorectal excision. OBJECTIVE: This study aimed to evaluate function and health-related quality of life among patients with rectal cancer treated with transanal total mesorectal excision. DESIGN: Consecutive patients treated between 2016 and 2018 were selected. Their function and quality of life were studied preoperatively and at 3 and 12 months after surgery. SETTING: This is a prospective case series. PATIENTS: Patients were eligible if they had primary anastomosis, their diverting stoma had been reversed, and they did not have anastomotic leakage. Forty-five patients were finally included. A total of 31 (68.8%) and 32 patients (71.1%) completed the 3- and 12-month surveys. INTERVENTIONS: Standard transanal total mesorectal excision was performed. MAIN OUTCOME MEASURES: The primary end point was functional and quality-of-life outcomes using validated questionnaires. Secondary end points included values obtained with endoanal ultrasounds, anorectal manometries, and rectal sensation testing. RESULTS: Wexner and Low Anterior Resection Syndrome scores significantly increased 3 months after surgery but returned to baseline values at 12 months. The rate of "major low anterior resection syndrome" at the end of follow-up was 25.0% (+11.7% compared with baseline, p = 0.314). Sexual and urinary functions remained stable throughout the study, although a meaningful clinical improvement was detected in male sexual interest. Among quality-of-life domains, all deteriorations returned to baseline values 12 months after surgery, except worsening of flatulence symptoms, and improvement in insomnia and constipation. At 12 months, an expected decrease in the mean width of the internal sphincter, the anal resting pressure, and the tenesmus threshold volume was found. LIMITATIONS: This study was limited by its small sample size, the absence of a comparative group, and significant missing data in female sexual difficulty and in ultrasounds and manometries at 3 months. CONCLUSIONS: Patients undergoing transanal total mesorectal excision report acceptable quality-of-life and functional outcomes 12 months after surgery. See Video Abstract at http://links.lww.com/DCR/B541. RESULTADOS FUNCIONALES Y CALIDAD DE VIDA DE LOS PACIENTES DESPUS DE LA ESCISIN MESORRECTAL TOTAL TRANSANAL PARA CNCER DE RECTO UN ESTUDIO PROSPECTIVO OBSERVACIONAL: ANTECEDENTES:Pocos estudios han abordado el impacto funcional después de la escisión mesorrectal total transanal.OBJETIVO:Evaluar la función y la calidad de vida relacionada con la salud en pacientes con cáncer de recto tratados con escisión mesorrectal total transanal.DISEÑO:Se seleccionaron pacientes consecutivos tratados entre 2016 y 2018. Se estudió su función y calidad de vida, en la etapa preoperatoria, a los tres y doce meses postoperatorios.METODO:Serie de casos prospectivos.PACIENTES:Los pacientes eran incluidos en presencia de anastomosis primaria, cierre del estoma de derivación y en ausencia de fuga anastomótica. Finalmente se incluyeron cuarenta y cinco pacientes. Un total de 31 (68,8%) y 32 pacientes (71,1%) completaron las encuestas de tres y doce meses, respectivamente.INTERVENCIONES:Escisión mesorrectal total transanal estándar.PRINCIPALES MEDIDAS DE RESULTADO:Los criterio de evaluación principal fueron los resultados funcionales y de calidad de vida mediante cuestionarios previamente validados. Los criterios de evaluación secundarios incluyeron los valores obtenidos con ecografía endoanal, manometría anorrectal y prueba de sensibilidad rectal.RESULTADOS:La escala de Wexner y el síndrome de resección anterior baja aumentaron significativamente tres meses después de la cirugía, pero volvieron a los valores iniciales a los doce meses. La tasa de "síndrome de resección anterior inferior grave" al final del seguimiento fue del 25,0% (+ 11,7% en comparación con el valor inicial, p = 0,314). La función sexual y urinaria se mantuvo estable durante todo el estudio, aunque se detectó una mejora clínica significativa en la libido masculina. Entre los criterios que evalúan la calidad de vida, todas las alteraciones en la misma volvieron a los valores iniciales, doce meses después de la cirugía, excepto el aumento de flatulencia, la mejoría del insomnio y el estreñimiento. A los doce meses, se encontró una disminución esperada en el grosor medio del esfínter interno, la presión anal en reposo y el volumen umbral para la presencia de tenesmo.LIMITACIONES:Tamaño de muestra limitado, ausencia de un grupo comparativo, falta significativa de datos para identificar la dificultad para la actividad sexual femenina y el efectuar ecografía y manometría a los tres meses.CONCLUSIONES:Los pacientes sometidos a escisión mesorrectal total transanal refieren una calidad de vida y resultados funcionales aceptables a los doce meses después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/B541.

Quantitative Indocyanine Green Fluorescence Imaging Assessment for Nonmucinous Peritoneal Metastases: Preliminary Results of the ICCP Study.

BACKGROUND: In selected patients with peritoneal metastases of colorectal origin, complete cytoreduction has been the main single prognostic factor influencing long-term outcomes. In these patients, indocyanine green fluorescence imaging seems to be useful in detecting small subclinical peritoneal implants. However, quantitative fluorescence analysis has not yet been established as standard. OBJECTIVE: This study aimed to evaluate the sensitivity and specificity of quantitative indocyanine green fluorescence assessment in the detection of peritoneal metastases of nonmucinous colorectal origin. DESIGN: This is a single-center, single-arm, low-intervention prospective trial. SETTINGS: A fluorescence assessment device was used for intraoperative fluorescence quantitative assessment. PATIENTS: Consecutive patients diagnosed with peritoneal metastases of colorectal origin who met the inclusion criteria were selected for curative surgery. INTERVENTIONS: Intravenous indocyanine green was administered 12 hours before surgery. Cytoreduction was performed through nodule identification under white light and then under indocyanine green. Finally, ex vivo fluorescence was assessed. MAIN OUTCOME MEASURES: The primary outcomes measured were the sensitivity and specificity of quantitative fluorescence. RESULTS: The first 11 enrolled patients were included in this preliminary analysis. In total, 52 nodules were resected, with 37 (71.1%) being diagnosed as malignant in the histopathological analysis. Of those, 5 (13.5%) were undetectable under white light and were identified only with fluorescence. A total of 15 nonmalignant nodules were detected under white light, 8 (53.3%) of which were fluorescence negative. Fluorescence greater than 181 units might be the threshold of malignancy, with a sensitivity and specificity of 89.0% and 85.0%, whereas uptake less than 100 units appears to correlate with a benign pathology. LIMITATIONS: The limited sample size, the physiological uptake, and excretion of indocyanine green might interfere with the assessment of unnoticed implants in the bowel serosa and liver. CONCLUSIONS: Quantitative indocyanine green seems to be useful for the assessment of nonmucinous colorectal peritoneal metastases. Fluorescence uptake greater than 181 units appears to correlate with malignancy, whereas uptake less than 100 units appears to correlate with a benign pathology. See Video Abstract at http://links.lww.com/DCR/B743. EVALUACIN CUANTITATIVA DE IMGENES DE FLUORESCENCIA CON VERDE DE INDOCIANINA PARA METSTASIS PERITONEALES NO MUCINOSAS RESULTADOS PRELIMINARES DEL ESTUDIO ICCP: ANTECEDENTES:En pacientes seleccionados con metástasis peritoneales de origen colorrectal, la citorreducción com-pleta ha sido el único factor pronóstico principal que influye en el resultado a largo plazo. En estos pacientes, las imágenes de fluorescencia con verde de indocianina parecen ser útiles para detectar pequeños implantes peritoneales subclínicos. Sin embargo, el análisis cuantitativo de fluorescencia aún no se ha establecido como estándar.OBJETIVO:Evaluar la sensibilidad y especificidad de la evaluación cuantitativa de fluorescencia verde de indo-cianina, en la detección de metástasis peritoneales de origen colorrectal no mucinoso.DISEÑO:Ensayo prospectivo de intervención baja de un solo brazo y un solo centro.ENTORNO CLINICO:El dispositivo se utilizó para la evaluación cuantitativa de fluorescencia intraoperatoria.PACIENTES:Pacientes consecutivos diagnosticados con metástasis peritoneales de origen colorrectal, selecciona-dos para cirugía curativa y que cumplieron con los criterios de inclusión.INTERVENCIONES:Se administró verde de indocianina por vía intravenosa 12 h antes de la cirugía. La citorreducción se realizó mediante identificación de nódulos con luz blanca y luego con verde de indocianina. Final-mente, se evaluó la fluorescencia ex vivo.PRINCIPALES MEDIDAS DE VALORACION:Sensibilidad y especificidad cuantitativa de la fluorescencia.RESULTADOS:Los primeros 11 pacientes fueron incluidos en este análisis preliminar. En total se resecaron 52 nódu-los, siendo 37 (71,1%) diagnosticados como malignos en el análisis histopatológico. De ellos, 5 (13,5%) eran indetectables bajo luz blanca y solamente se identificaron con fluorescencia. Se detec-taron un total de 15 nódulos no malignos bajo luz blanca, de los cuales 8 (53,3%) fueron fluorescen-tes negativos. La fluorescencia superior a 181 unidades podría ser el umbral de malignidad, con una sensibilidad y especificidad del 89,0% y el 85,0% respectivamente; mientras que la captación por debajo de 100 unidades parece correlacionarse con una patología benigna.LIMITACIONES:El tamaño limitado de la muestra; la captación fisiológica y la excreción de verde de indocianina pueden interferir con la evaluación de implantes inadvertidos en la serosa intestinal y el hígado.CONCLUSIONES:La cuantificación del verde de indocianina, parece ser útil en la evaluación de metástasis peritonea-les colorrectales no mucinosas. La captación de fluorescencia por encima de 181 unidades parece correlacionarse con la malignidad, mientras que la captación por debajo de 100 unidades parece co-rrelacionarse con una patología benigna. Consulte Video Resumen en http://links.lww.com/DCR/B743. (Traducción - Dr. Fidel Ruiz Healy).

Transanal total mesorectal excision for stage II or III rectal cancer: pattern of local recurrence in a tertiary referral center.

BACKGROUND: For mid and low rectal cancer, transanal total mesorectal excision (TaTME) has been established as an alternative approach to laparoscopic surgery. However, there are concerns about an unexpected pattern of local recurrence. This study aimed to analyze the pattern of local recurrence for patients treated with TaTME in a tertiary referral center. METHODS: A retrospective single-center analysis was performed. Since 2011, all patients with rectal cancer undergoing TaTME with curative intent were prospectively included in a standardized database. Patients with tumors within 12 cm, clinical stage II or III were included. The primary endpoint of the study was the overall local recurrence rate, together with a critical analysis of the patterns of local failures. RESULTS: Two hundred and five patients were included in this analysis. At the time of surgery, patients had a mean age of 67.1 years (SD 12.3), and 66.8% were male. Neoadjuvant therapy was administered in 73.7%. Mesorectal specimen quality was complete or near-complete in 98.5%, while circumferential resection margin was ≤ 1 mm (including T4 tumors) in 11.8%. After a median follow-up of 34.3 months (95% CI 30.1-38.5), 3.4% (n = 7) presented with local recurrent disease. Six out of the seven patients were also diagnosed with hematogenous metastases. Of the seven patients, three presented with at least one of the following risk factors: T4 tumor, N2 disease, incomplete mesorectal specimen, or positive CRM. Local failure was noted posteriorly (n = 3), laterally (n = 2), anteriorly (n = 1), and in the axial compartment (n = 1). Median time to relapse was 31.5 months (10.3-40.9). The median follow-up after local recurrence was 7.9 (95% CI 6.7-9.1) months, with an overall survival of 85.7%. CONCLUSIONS: TaTME provided satisfactory local recurrence outcomes, and the most common patterns of failure were in the central pelvis.

Giant Gastric Gastrointestinal Stromal Tumor (GIST).

Gastrointestinal stromal tumors (GIST) represent 0.1-3 % of gastrointestinal malignancy. Surgery is the mainstay of treatment, but in high-risk tumors, imatinib can help to achieve better oncological outcomes. We present a rare case of a patient with gastric GIST with very aggressive evolution in a short period of time despite the use of neoadjuvant therapy with imatinib.

[Effects of gastric bypass on estimated cardiovascular risk in morbidly obese patients with metabolic syndrome]. / Efectos del bypass gástrico sobre el riesgo cardiovascular estimado.

INTRODUCTION: The major goal of surgical treatment in morbid obesity is to decrease morbidity and mortality associated with excess weight. In this sense, the main factors of death are cardiovascular disease and metabolic syndrome. The objective of this study is to evaluate the effects of gastric bypass on cardiovascular risk estimation in patients after bariatric surgery. MATERIAL AND METHODS: We retrospectively evaluated pre and postoperative cardiovascular risk estimation of 402 morbidly obese patients who underwent laparoscopic gastric bypass. The major variable studied is the cardiovascular risk estimation that is calculated preoperatively and after 12 months. Cardiovascular risk estimation analysis has been performed with the REGICOR Equation. REGICOR formulation allows calculating a 10 year risk of cardiovascular events adapted to the Spanish population and is expressed in percentages. RESULTS: We reported an overall 4.1±3.0 mean basal REGICOR score. One year after the operation, cardiovascular risk estimation significantly decreased to 2,2±1,6 (P<.001). In patients with metabolic syndrome according to ATP-III criteria, basal REGICOR score was 4.8±3.1 whereas in no metabolic syndrome patients 2.2±1.8. Evaluation 12 months after surgery, determined a significant reduction in both groups (metabolic syndrome and non metabolic syndrome) with a mean REGICOR score of 2.3±1.6 and 1.6±1.0 respectively. CONCLUSION: The results of our study demonstrate favorable effects of gastric bypass on the cardiovascular risk factors included in the REGICOR equation.

MA-NOS radical sigmoidectomy: report of a transvaginal resection in the human.

BACKGROUND: With available laparoscopic and endoscopic instruments/technology a standard radical sigmoid resection is feasible and safe using transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS). METHODS: The intervention was a transvaginal MA-NOS sigmoidectomy in a 78-year-old woman with a sigmoid adenocarcinoma. Maintaining triangulation the surgeon positioned himself at the right side of the patient and used the transvaginal trocar for dissection and stapling of both the inferior mesenteric vessels and the upper rectum. The colonic resection was performed extracorporeally in the conventional fashion and was followed by an intra-abdominal endoscopically assisted stapled anastomosis. RESULTS: Advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All oncological principles governing resection and management were accomplished and the pathology examination confirmed a T3N1 lesion. The patient was discharged on the fourth postoperative day. CONCLUSION: Transvaginal MA-NOS radical sigmoidectomy is a feasible and oncologically safe procedure. MA-NOS is a realistic option for avoiding the need of assisting incisions and related morbidity in the laparoscopic resection of large intra-abdominal lesions. Combined hybrid laparoscopic NOS in humans (MA-NOS) currently provides a safe and reliable way of defining future clinical applications and advantages of NOS and NOTES. Additionally, it stimulates the active development and evaluation of the underpinning technologies and instrumentation.

[Planning, management and results of the implantation of laparoscopic surgery of the colon and rectum in a general hospital]. / Planificación, gestión y resultados de la implantación de la cirugía laparoscópica de colon y recto en un hospital general.

INTRODUCTION: The introduction of laparoscopic surgery in a hospital is a slow process requiring the involvement of a multidisciplinary team. PATIENTS AND METHOD: We performed a prospective, descriptive study of all patients who underwent laparoscopic surgery of the colon and rectum in the Mataró Hospital between 2003 and 2006. We also describe the model used to introduce laparoscopic surgery of the colon and rectum in our center. RESULTS: Between 2003 and 2006, 166 patients with colorectal disease underwent laparoscopic surgery. Patients included for rectal disease represented 36% of the total. The conversion rate was 7% of the mean in all the periods studied, with a complications rate of 13.25%. CONCLUSIONS: The controlled development of laparoscopic surgery allows satisfactory results to be obtained in colorectal disease.

The effect of normothermic recirculation is mediated by ischemic preconditioning in NHBD liver transplantation.

We have evaluated the involvement of hepatic preconditioning mediators (adenosine, adenosine A1 and A2 receptors) during normothermic recirculation (NR) in a model of liver transplantation from non-heart-beating donor (NHBD) pigs. Application of NR after 20 min of warm ischemia (WI) reversed the lethal injury associated with transplantation of NHBD livers (achieving 5-day survival and diminishing glutathione S-transferase (GST), aspartate aminotransferase (AST) and hyaluronic acid (HA)). Adenosine administration prior to WI simulated the effect of NR. Measuring adenosine, we found that during NR, hepatic adenosine levels increased and xanthine levels decreased. Then when we blocked A2 receptors the effect of NR was abolished, whereas the blocking of A1 receptors further protected the liver. Furthermore, A2 blocking improved hepatic perfusion during NR whereas A1 blocking reduced it. The study suggests that NR has a preconditioning effect by maintaining adequate adenosine and xanthine levels. During NR, adenosine protects the liver through A2 activation and damages it through A1 activation although simultaneous stimulation of both receptors exerts a clear beneficial effect. The possible relation of NR mechanism with other preconditioning mediators such as cAMP and nitric oxide synthesis are discussed.

Hepatic preconditioning after prolonged warm ischemia by means of S-adenosyl-L-methionine administration in pig liver transplantation from non-heart-beating donors.

BACKGROUND: This study ascertained the effect of S-adenosyl-L-methionine (SAMe) administration on the ischemia-reperfusion injury associated with pig liver transplantation from non-heart-beating donors (NHBDs) after prolonged warm ischemia. METHOD: Twenty-five animals underwent transplantation with an allograft from an NHBD. After donor cardiac arrest, cardiopulmonary bypass and normothermic recirculation (NR) were performed for 30 min. Ten animals were given SAMe during NR. Donors were cooled to 15 degrees C, and liver procurement was performed. RESULTS: SAMe reduced histologic liver damage 5 days after transplantation. The necrotic area affected 15.9%+/-14.5% of the liver biopsies in controls and 7.4%+/-9% in SAMe livers. Six of eight controls and only one of eight survivors in the SAMe group developed ischemic cholangitis. SAMe reduced apoptosis of hepatocytes 5 days after transplantation and apoptosis of sinusoidal endothelial cells at reperfusion and at 5 days. SAMe increased energy charge at the end of NR and favored the balance between adenosine and xanthine. It was also associated with higher portal blood flow (740+/-59.2 vs. 475.2+/-65.0 mL/min-1/m-2), hepatic hyaluronic acid extraction (132+/-72.2 vs. -205.8+/-64.6 microg/L), and lower levels of alpha-glutathione-S-transferase after reperfusion (2,601%+/-581% with respect to baseline vs. 6,488%+/-5,612%). CONCLUSION: SAMe administration during liver procurement from NHBDs prevents liver endothelial, parenchymal, and biliary tract damage. The protective role of SAMe may be partially mediated by the effect of adenosine during liver procurement.