Association between plane of mesocolic dissection and recurrence after complete mesocolic excision for right-sided colon cancer: a cohort study.

AIM: Dissection in the mesocolic plane is considered by some medical professionals to be crucial in complete mesocolic excision. We aimed to assess whether intramesocolic plane dissection is associated with a risk of recurrence after complete mesocolic excision for right-sided colon cancer. METHOD: This is a single-centre study based on prospectively registered data on patients undergoing resection for Union for International Cancer Control Stage I-III right-sided colon adenocarcinoma during the period 2010-2017. Patients were stratified in an intramesocolic plane group or a mesocolic plane group based on a prospective assessment of fresh specimens by a pathologist. Primary outcome was the 4.2 year risk of recurrence after inverse probability treatment weighting and competing risk analyses. RESULTS: Of 383 patients, 4 (1%) were excluded as the specimen was assessed as muscularis propria plane, 347 (91.6%) specimens were deemed as mesocolic and 32 (8.4%) as intramesocolic. The 4.2 year cumulative incidence of recurrence after inverse probability treatment weighting was 9.1% (95% CI 6.0%-12.1%) in the mesocolic group compared with 14.0% (3.6%-24.5%) in the intramesocolic group with an absolute risk difference in favour of mesocolic plane dissection of 4.9% (-5.7 to 15.6, p = 0.37). No difference was observed in the risk of local recurrence, death before recurrence or overall survival after 4.2 years between the two groups. CONCLUSION: Mesocolic plane dissection can be achieved in more than 90% of patients. The classification seems to be a guide for good surgical practice and not to be used for research purposes.

Validation of the German classification system for quality assessment of right-sided colon cancer specimens.

AIM: The German classification system of the completeness of mesocolic excision aims to assess the quality of right-sided colonic cancer surgery by review of photographs. We aimed to validate the reliability of the classification in a clinical context. METHOD: The study was based on a cohort of patients undergoing resection for right-sided colon cancer in two university hospitals served by the same group of pathologists. Prospectively collected photographs of the specimens were assessed twice by six colorectal surgeons to determine the intra-rater and inter-rater accuracy of the German classification and a modification assessing extended right-sided resections. RESULTS: Specimens from 613 resections for right-sided colon cancer were reviewed. Twenty-one specimens were found to be non-assessable, leaving 436 right hemicolectomies, 139 extended right hemicolectomies and 17 right-sided subtotal colectomies. Intra-rater reliability was 0.57-0.74 and weighted kappa coefficients 0.58-0.74, without differences between subgroups. The percentage of agreement between all six participants was 20.3% for all specimens, 21.1% for right hemicolectomy specimens and 18.1% for extended hemicolectomy and right-sided subtotal colectomy specimens. For the right hemicolectomy specimens, the model-based kappa coefficient for agreement was 0.27 (95% CI 0.24-0.30) and for association 0.45 (95% CI 0.41-0.49). CONCLUSION: The German classification of right hemicolectomy specimens showed low intra-rater reliability and inter-rater agreement and association. The use of this classification for scientific purposes appeared not to be reliable.

Nonmicroradical Resection Margin as a Predictor of Recurrence in Patients With Stage III Colon Cancer Undergoing Complete Mesocolic Excision: A Prospective Cohort Study.

BACKGROUND: The prognostic value of the present definition of microradicality in colon cancer is poorly understood, especially considering the vast influence it has in rectal cancer prognosis. OBJECTIVE: This study aimed to investigate whether the risk of recurrence after complete mesocolic excision for stage III colon cancer is associated with the distance from tumor tissue to resection margin and whether the location of the involved margin is of any significance. DESIGN: A prospective cohort of patients was stratified into 2 groups to distinguish between direct margin invasion (0-mm resection margin) and a ≤1-mm resection margin without direct invasion or 3 groups to distinguish between the location of margin involvement (lateral tumor resection margin, central vascular ligation margin, and nonperitonealized mesocolic resection margin). Patients with microradical resections were used as a control group. SETTINGS: We included all patients undergoing elective complete mesocolic excision for International Union Against Cancer stage III colon cancer at Nordsjællands Hospital between January 1, 2008, and December 31, 2016. PATIENTS: A total of 276 patients met all inclusion criteria and none of the exclusion criteria. MAIN OUTCOME MEASURES: Primary outcome was risk of recurrence after 3.2 years. RESULTS: A total of 41 patients (15%) had a nonmicroradical resection. The 3.2-year cumulative incidence of recurrence for a 0-mm margin was 43% and 24% for a ≤1-mm margin without direct invasion, corresponding with an HR of 4.3 (p = 0.0146) and 1.3 (p = 0.474). The location of the involved margin showed no significant differences. LIMITATIONS: This was a single-center study containing a limited number of patients with a nonmicroradical resection with a risk of type II error. CONCLUSIONS: We found no increased risk of recurrence for a ≤1-mm margin without direct invasion, indicating that the present classification of microradicality might not be justified if an intact posterior mesocolic fascia without invasion of tumor tissue is present. See Video Abstract at http://links.lww.com/DCR/B625. MARGEN DE RESECCIN NO MICRORRADICAL COMO PREDICTOR DE RECURRENCIA EN PACIENTES CON CNCER DE COLON EN ESTADIO III SOMETIDOS A ESCISIN MESOCLICA COMPLETA UN ESTUDIO DE COHORTE PROSPECTIVO: ANTECEDENTES:El valor pronóstico de la definición actual de microrradicalidad en el cáncer de colon es poco conocido, especialmente considerando la gran influencia que tiene en el pronóstico del cáncer de recto.OBJETIVO:Este estudio tiene como objetivo investigar si el riesgo de recurrencia después de la escisión mesocólica completa (CME) para el cáncer de colon en estadio III está asociado con la distancia desde el tejido tumoral hasta el margen de resección y si la localización del margen afectado tiene alguna importancia.DISEÑO:Una cohorte prospectiva de pacientes se estratificó en dos grupos para distinguir entre la invasión del margen directo (margen de resección de 0 mm) y un margen de resección ≤1 mm sin invasión directa, o tres grupos para distinguir entre la localización de la afectación del margen (resección lateral del margen del tumor, margen de ligadura vascular central y margen de resección mesocólica no peritonizada). Los pacientes con resecciones microrradicales se utilizaron como grupo control.ENTORNO CLÍNICO:Incluimos a todos los pacientes sometidos a CME electiva por cáncer de colon en estadio III de la UICC en el Hospital Nordsjællands, Dinamarca, entre el 1 de enero de 2008 y el 31 de diciembre de 2016.PACIENTES:Un total de 276 pacientes cumplieron todos los criterios de inclusión y ninguno de los criterios de exclusión.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el riesgo de recurrencia después de 3 · 2 años.RESULTADOS:Un total de 41 (15%) pacientes tuvieron una resección no microrradical. La incidencia acumulada de recurrencia a los 3,2 años para un margen de 0 mm fue del 43% y del 24% para un margen ≤1 mm sin invasión directa, lo que corresponde a un cociente de riesgo de 4,3 (p = 0,0146) y 1,3 (p = 0,474) respectivamente. La localización del margen afectado no mostró diferencias significativas.LIMITACIONES:Estudio unicéntrico con un número limitado de pacientes con resección no microrradical con riesgo de error tipo II.CONCLUSIONES:No encontramos un mayor riesgo de recurrencia para un margen ≤1 mm sin invasión directa, lo que indica que la clasificación actual de microrradicalidad podría no estar justificada si está presente una fascia mesocólica posterior intacta sin invasión del tejido tumoral. Consulte Video Resumen en http://links.lww.com/DCR/B625. (Traducción-Dr Yazmin Berrones-Medina).

Plane of mesocolic dissection as predictor of recurrence after complete mesocolic excision for sigmoid colon cancer: A cohort study.

AIM: To investigate whether intramesocolic plane dissection assessed on fresh specimens by the pathologist is a risk factor for recurrence after complete mesocolic excision for sigmoid cancer when compared with mesocolic plane dissection. METHOD: Single-centre study based on prospectively registered data on patients undergoing resection for UICC stage I-III sigmoid colon adenocarcinoma during the period 2010-2017. The patients were stratified into either an intramesocolic plane group or a mesocolic plane group. Primary outcome was risk of recurrence after 4.2 years using inverse probability treatment weighting and competing risk analyses. RESULTS: Of a total of 332 patients, two were excluded as the specimen was assessed as muscularis propria plane, 237 (72%) specimens were deemed as mesocolic and 93 (28%) as intramesocolic. The 4.2-year cumulative incidence of recurrence after inverse probability treatment weighting was 14.9% (10.4-19.3) in the mesocolic group compared with 9.4% (3.7-15.0) in the intramesocolic group, thus the absolute risk difference between the mesocolic plane and intramesocolic plane was 5.5% (-12.5-1.6; p = 0.13) in favour of the intramesocolic group. CONCLUSION: Intramesocolic plane dissection was not a risk factor for recurrence after complete mesocolic excision for sigmoid cancer when compared with mesocolic plane dissection. No difference in risk of local recurrence, death before recurrence, and in overall survival after 4.2 years was observed between the two groups. With less than 1% of the specimens deemed as muscularis propria plane dissection, the classification appears unusable for the risk prediction of sigmoid colon cancer.

5-year outcome after complete mesocolic excision for right-sided colon cancer: a population-based cohort study.

BACKGROUND: The benefits of extensive lymph node dissection as performed in complete mesocolic excision are still debated, although recent studies have shown an association with improved long-term outcomes. However, none of these studies had an intention-to-treat design or aimed to show a causal effect; therefore in this study, we aimed to estimate the causal oncological treatment effects of complete mesocolic excision on right-sided colon cancer. METHODS: We did a population-based cohort study involving prospective data collected from four hospitals in Denmark. We compared the oncological outcome data of patients at one centre performing central lymph node dissection and vascular division after almost complete exposure of the proximal part of the superior mesenteric vein (ie, the complete mesocolic excision group) with three other centres performing conventional resections with unstandardised and limited lymph node dissection (ie, non-complete mesocolic excision; control group). We included data for all patients in the Capital Region of Denmark undergoing elective curative-intent right-sided colon resections for stages I-III colon cancer, as categorised by the Union for International Cancer Control (UICC; 5th edition), from June 1, 2008, to Dec 31, 2013. Patients were followed-up for 5·2 years after surgery. The primary outcome was the cumulative incidence of recurrence after 5·2 years of surgery. Inverse probability of treatment weighting and competing risk analyses were used to estimate the possible causal effects of complete mesocolic excision. This study is registered with ClinicalTrials.gov, number NCT03754075. FINDINGS: 1069 patients (813 in the control group and 256 in the complete mesocolic excision group) underwent curative-intent elective surgery for right-sided colon cancer during the study period. None of the patients were lost to follow-up regarding survival or recurrence status, and consequently no patient was censored in the analyses. The 5·2-year cumulative incidence of recurrence was 9·7% (95% CI 6·3-13·1) in the complete mesocolic excision group compared with 17·9% (15·3-20·5) in the control group, and the absolute risk reduction of complete mesocolic excision after 5·2 years was 8·2% (95% CI 4·0-12·4; p=0·00015). In the control group, 145 (18%) of 813 patients were diagnosed with a recurrence and 281 (35%) died during follow-up, whereas in the complete mesocolic excision group 25 (10%) of 256 patients were diagnosed with a recurrence and 75 (29%) died during follow-up. INTERPRETATION: This study shows a causal treatment effect of central mesocolic lymph node excision on risk of recurrence after resection for right-sided colon adenocarcinoma. Complete mesocolic excision has the potential to reduce the risk of recurrence and improve long-term outcome after resection for all UICC stages I-III of right-sided colon adenocarcinomas. FUNDING: The Tvergaard Fund, Helen Rude Fund, Krista and Viggo Petersen Fund, Olga Bryde Nielsen Fund, and Else and Mogens Wedell-Wedellsborg Fund.

Disease-free survival after complete mesocolic excision compared with conventional colon cancer surgery: a retrospective, population-based study.

BACKGROUND: Application of the principles of total mesorectal excision to colon cancer by undertaking complete mesocolic excision (CME) has been proposed to improve oncological outcomes. We aimed to investigate whether implementation of CME improved disease-free survival compared with conventional colon resection. METHODS: Data for all patients who underwent elective resection for Union for International Cancer Control (UICC) stage I-III colon adenocarcinomas in the Capital Region of Denmark between June 1, 2008, and Dec 31, 2011, were retrieved for this population-based study. The CME group consisted of patients who underwent CME surgery in a centre validated to perform such surgery; the control group consisted of patients undergoing conventional colon resection in three other hospitals. Data were collected from the Danish Colorectal Cancer Group (DCCG) database and medical charts. Patients were excluded if they had stage IV disease, metachronous colorectal cancer, rectal cancer (≤ 15 cm from anal verge) in the absence of synchronous colon adenocarcinoma, tumour of the appendix, or R2 resections. Survival data were collected on Nov 13, 2014, from the DCCG database, which is continuously updated by the National Central Office of Civil Registration. FINDINGS: The CME group consisted of 364 patients and the non-CME group consisted of 1031 patients. For all patients, 4-year disease-free survival was 85.8% (95% CI 81.4-90.1) after CME and 75.9% (72.2-79.7) after non-CME surgery (log-rank p=0.0010). 4-year disease-free survival for patients with UICC stage I disease in the CME group was 100% compared with 89.8% (83.1-96.6) in the non-CME group (log-rank p=0.046). For patients with UICC stage II disease, 4-year disease-free survival was 91.9% (95% CI 87.2-96.6) in the CME group compared with 77.9% (71.6-84.1) in the non-CME group (log-rank p=0.0033), and for patients with UICC stage III disease, it was 73.5% (63.6-83.5) in the CME group compared with 67.5% (61.8-73.2) in the non-CME group (log-rank p=0.13). Multivariable Cox regression showed that CME surgery was a significant, independent predictive factor for higher disease-free survival for all patients (hazard ratio 0.59, 95% CI 0.42-0.83), and also for patients with UICC stage II (0.44, 0.23-0.86) and stage III disease (0.64, 0.42-1.00). After propensity score matching, disease-free survival was significantly higher after CME, irrespective of UICC stage, with 4-year disease-free survival of 85.8% (95% CI 81.4-90.1) after CME and 73.4% (66.2-80.6) after non-CME (log-rank p=0·0014). INTERPRETATION: Our data indicate that CME surgery is associated with better disease-free survival than is conventional colon cancer resection for patients with stage I-III colon adenocarcinoma. Implementation of CME surgery might improve outcomes for patients with colon cancer. FUNDING: Tvergaards Fund and Edgar and Hustru Gilberte Schnohrs Fund.

Lymph node metastases in the gastrocolic ligament in patients with colon cancer.

BACKGROUND: Long-term survival after colorectal cancer may be improved by more extensive resection of the primary tumor and lymph nodes. Resection of the gastroepiploic and infrapyloric lymph nodes in the gastrocolic ligament has been proposed as a standard procedure when resecting tumors located in the proximity of the flexures or in the transverse colon. OBJECTIVE: The purpose of this work was to present our findings of metastases in the gastrocolic ligament in a consecutive series of patients. DESIGN: This was a single-center retrospective study. SETTINGS: The study was conducted in a colorectal cancer center. PATIENTS: All of the colon adenocarcinoma resections with relevant tumor location from June 1, 2008, to December 31, 2012 were included in this study. MAIN OUTCOME MEASURES: The presence of lymph node metastases in the gastrocolic ligament in colon adenocarcinomas located in the proximity of the flexures or in the transverse colon was measured. RESULTS: Gastrocolic resection was performed in 130 patients. Thirty-two patients were excluded because of a lack of information about gastrocolic lymph node status in the pathology reports. Median age of the remaining 98 patients was 70 years (range, 30-90 years), and 57% were men. Gastrocolic lymph nodes were found in 86 specimens (88%) with a median number of 4 lymph nodes (range, 0-16 lymph nodes). Thirty-four patients (35%) had mesocolic lymph node metastases. Gastrocolic lymph node metastases were found in 4 (12%) of these 34 patients and in 4% of all 98 included patients. Gastrocolic lymph node metastases were related to perineural invasion (p > 0.001). LIMITATIONS: Limitations of this study include the retrospective design, size of material, and lack of gastrocolic ligament lymph node status in the pathology report in some patients. CONCLUSIONS: Metastases in the gastroepiploic or infrapyloric lymph nodes can be found in patients with tumors located in the proximity of the flexures or in the transverse colon. Further studies are needed to reveal the clinical relevance of this finding, with special focus on recurrence risk and long-term survival.