Impact of a multidisciplinary training programme on outcome of upper rectal cancer by critical appraisal of the extent of mesorectal excision with postoperative MRI.

BACKGROUND: Optimal management of patients with upper rectal cancer remains unclear. Partial mesorectal excision (PME) without neoadjuvant therapy is currently advocated for the majority of patients. Recent studies, however, reported a high risk of local recurrence and suboptimal surgery. The aim of this study was to evaluate the effects of a quality assurance initiative with postoperative MRI to improve outcomes in these patients. METHODS: Patients who underwent mesorectal excision with curative intent for rectal cancer in 2007-2013 were included. Postoperative MRI of the pelvis was performed 1 year after surgery. In 2011, a multidisciplinary workshop with focus on extent and completeness of surgery was held for training surgeons, pathologists and radiologists involved in treatment planning. Images of residual mesorectum and histopathological reports were reviewed with regard to the distal resection margin. Local recurrence after a minimum of 3 years' follow-up was compared between two cohorts from 2007-2010 and 2011-2013. RESULTS: A total of 627 patients were included; postoperative MRI of the pelvis was done in 381 patients. The 3-year actuarial local recurrence rate in patients with upper rectal cancer improved from 12·9 to 5·0 per cent (P = 0·012). After the workshop, fewer patients with cancer of the upper rectum were selected to have PME (90·8 per cent in 2007-2010 versus 80·2 per cent in 2011-2013; P = 0·023), and fewer patients who underwent PME had an insufficient distal resection margin (61·7 versus 31 per cent respectively; P < 0·001). CONCLUSION: Quality assessment of surgical practice may have a major impact on oncological outcome after surgery for upper rectal cancer.

ANTECEDENTES: El tratamiento óptimo para los pacientes con cáncer del tercio superior de recto no está claro. En este momento, la conducta más empleada es la exéresis parcial del mesorrecto (partial mesorectal excision, PME) sin tratamiento neoadyuvante. Sin embargo, estudios recientes han apuntado que se trata de una cirugía subóptima con un elevado riesgo de recidiva local. El objetivo de este estudio fue evaluar los efectos de una iniciativa de control de calidad con una resonancia magnética (magnetic resonance imaging, MRI) postoperatoria para mejorar los resultados en estos pacientes. MÉTODOS: Se incluyeron los pacientes con cáncer rectal a los que se realizó una exéresis del mesorrecto con intención curativa entre los años 2007 y 2013. Un año después de la cirugía se realizó una MRI de la pelvis. En el 2011, se organizó un taller multidisciplinario para educar a los cirujanos, patólogos y radiólogos involucrados en la planificación del tratamiento, en el que se discutieron la extensión y la radicalidad de la cirugía. Se revisaron las imágenes de mesorrecto residual y los informes histopatológicos respecto al margen de resección distal. Se comparó la recidiva local después de más de 3 años de seguimiento entre dos cohortes temporales, 2007-2010 y 2011-2013, respectivamente. RESULTADOS: Se incluyeron un total de 627 pacientes, en los que en 381 se realizó una MRI postoperatoria de la pelvis. Las tasa actuarial de recidiva local a 3 años en pacientes con cáncer del tercio superior de recto mejoraron del 12,9% al 5,0% (P = 0,012). Después del taller, se realizaron menos PME en pacientes con cáncer del tercio superior de recto (91% versus 80%, P = 0,023) y menos pacientes en los que se realizó una PME presentaron un margen de resección distal insuficiente (62% versus 31%, P < 0,001). CONCLUSIÓN: La evaluación de la calidad de la práctica quirúrgica puede tener un gran impacto en los resultados oncológicos después de la cirugía del cáncer del tercio superior de recto.

Overall risk and risk factors for metachronous peritoneal metastasis after colorectal cancer surgery: a nationwide cohort study.

BACKGROUND: This study aimed to identify the cumulative incidence and risk factors of metachronous peritoneal metastasis (M-PM) from colorectal cancer in patients who had intended curative treatment. METHODS: Patients with colorectal cancer were identified using the Danish Colorectal Cancer Group database for 2006-2015. The Danish Pathology Registry and the Danish National Patient Registry were used to identify M-PM to 2017. Risk factors were estimated by multivariable absolute risk regression, treating death and other cancers as competing risks. Overall risk and risk differences (RDs) were estimated at 1, 3 and 5 years. RESULTS: In 22 586 patients with colorectal cancer, the overall risk of M-PM was reported to be 0·9 (95 per cent c.i. 0·8 to 1·0) per cent at 1 year, 1·9 (1·8 to 2·1) per cent at 3 years and 2·2 (2·0 to 2·4) per cent at 5 years. Advanced tumour category ((y)pT4 versus (y)pT1) increased the RD of both M-PM (2·9 (95 per cent c.i. 2·1 to 3·7) at 1 year and 6·0 (4·9 to 7·2) at 3 years) and lymph node involvement ((y)pN2 versus (y)pN0) (2·5 (1·8 to 3·2) at year and 4·3 (3·2 to 5·3) at 3 years). No further increase in risk was observed at 5 years. In a subanalysis, tumour-involved resection margin (R1 versus R0) was associated with M-PM with a RD of 3·9 (1·6 to 6·2) at 1 year and 5·9 (2·6 to 9·3) at 3 years. CONCLUSION: The overall risk of M-PM in patients with colorectal cancer is low, but is increased in advanced T and N status. Follow-up of at least 3 years after colorectal cancer surgery may be necessary, given the potential curative treatment of early diagnosed M-PM.

ANTECEDENTES: Este estudio tuvo como objetivo identificar la incidencia acumulada y los factores de riesgo de metástasis peritoneales metacrónicas (metachronous peritoneal metastases, M-PM) del cáncer colorrectal en pacientes que se sometieron al tratamiento curativo previsto. MÉTODOS: Se identificaron los pacientes con cáncer colorrectal a partir de la base de datos del grupo danés de cáncer colorrectal (Danish Colorectal Cancer Group) durante el periodo 2006-2015. El Registro Danés de Patología (Danish Pathology Registry) y el Registro Nacional Danés de Pacientes (Danish National Patient Registry) se utilizaron para identificar los casos de M-PM hasta el 2017. Los factores de riesgo se estimaron mediante una regresión de riesgo absoluto multivariable, tratando la muerte y otros tipos de cáncer como riesgos competitivos. El riesgo general y las diferencias de riesgo (risk differences, RD) se estimaron a 1, 3 y 5 años. RESULTADOS: De los 22.586 pacientes con CCR, el riesgo global de M-PM fue del 0,9% (i.c. del 95%: 0,8 a 1,0) al año, 1,9 (i.c. del 95%: 1,8 a 2,1) a los 3 años y 2,2 (i.c. del 95%: 2,0 a 2.4) después de 5 años. El estadio T tumoral avanzado ((y) pT4 versus (y) pT1) aumentó el riesgo de M-PM, DR a 1 año: 2,9% (i.c. del 95%: 2,1 a 3,), 3 años: 6,0 (i.c. 95% 4,9 a 7,2), así como la afectación de los ganglios linfáticos ((y) pN2 versus (y) pN0), 1 año: 2,5 (i.c. 95% 1,8 a 3,2), 3 años: 4,3 (i.c. 95% 3,2 a 5,3). No se observó un aumento adicional en la DR después de 5 años. Los márgenes de resección tumoral (R1 versus R0) se asociaron con una DR a 1 año de 3,9 (i.c. del 95% 1,6 a 6,2), y a 3 años de 5,9 (i.c. del 95% 2,6 a 9,3) de riesgo de M-PM en un subanálisis. CONCLUSIÓN: El riesgo global de M-PM en el cáncer colorrectal en pacientes es bajo, pero aumenta en las categorías de estadios T y N avanzados. Puede ser necesario un seguimiento de al menos 3 años después de la cirugía de CCR, dado el tratamiento potencialmente curativo de la M-PM diagnosticada precozmente.

Mucosal and systemic immune modulation by Trichuris trichiura in a self-infected individual.

Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h)1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity.

Suboptimal surgery and omission of neoadjuvant therapy for upper rectal cancer is associated with a high risk of local recurrence.

AIM: The aim of the present study was to estimate the risk of local recurrence in an audited cohort of patients, with a particular focus on patients with upper rectal cancer treated by partial mesorectal excision without neoadjuvant therapy. METHOD: Perioperative clinical data on all patients who underwent mesorectal excision for primary adenocarcinoma of the rectum in the period from 2007 to 2010 were prospectively collected and follow-up data on oncological outcome were retrieved from patient records. Three-year actuarial local recurrence rates were estimated using Kaplan-Meier methods. RESULTS: Local recurrence was diagnosed in 17 of 247 patients treated with curative intent. The 3-year actuarial local recurrence rate was 7.0% (95% CI 4.0-11.8). The risk of local recurrence was negatively associated with tumour stage (P = 0.015), an involved circumferential resection margin (P = 0.007) and tumour height (P = 0.044). The local recurrence rate at 3 years was 13.5% after partial mesorectal excision, 2.9% following total mesorectal excision and 5.7% after extralevator abdominoperineal excision (P = 0.032). CONCLUSION: Tumour stage and an involved circumferential resection margin were the most important predictors of local recurrence. For cancer of the upper rectum, partial mesorectal excision was associated with a high risk of local recurrence.

Implementation of complete mesocolic excision at a university hospital in Denmark: An audit of consecutive, prospectively collected colon cancer specimens.

AIM: Over recent years there has been a new focus on the quality of colon cancer surgery following the description and introduction of complete mesocolic excision (CME). In the same period, laparoscopic surgery has been widely applied to the treatment of colon cancer. We aimed to evaluate the introduction of both CME and laparoscopic-assisted surgery at Aarhus University Hospital, Denmark between 2008 and 2011. Secondly we aimed to evaluate the impact on the quality of surgery of post-operative team meetings where pathologists demonstrated the plane of surgery on the specimens. METHOD: A series of 209 consecutive and prospectively collected colon cancer specimens were evaluated by assessing the plane of surgery and measuring the amount of tissue resected. Multivariate analyses were used to control for influencing factors. RESULTS: The proportion of specimens resected in the mesocolic plane was high and increased significantly following the introduction of post-operative team meetings (52%-76%, p = 0.02). Laparoscopic surgery enhanced the distance between the tumour and the arterial tie by a mean of 27 mm (p < 0.0001) and the distance between the nearest bowel wall and the arterial tie by 26 mm (p < 0.0001) when compared to an open approach. Factors such as body mass index and age influenced the outcome for surgical quality. CONCLUSION: Implementation of CME and laparoscopic-assisted surgery for colon cancer is a challenge and requires continuous training and feedback. Post-operative multidisciplinary team meetings may be a key element in this process.

Extent and completeness of mesorectal excision evaluated by postoperative magnetic resonance imaging.

BACKGROUND: The major advance in rectal cancer management over the past 20 years has been the standardization of mesorectal excision. The aim of this study was to determine the prevalence and localization of inadvertent residual mesorectum detected on magnetic resonance imaging (MRI) after rectal cancer surgery. METHODS: Postoperative T2-weighted MRI of the pelvis was performed on patients following mesorectal excision. A multidisciplinary team radiologist evaluated the images with regard to residual mesorectum and distal margin. Only mesorectum above the level of the anastomosis perpendicular to the bowel was regarded as inadvertent residual mesorectum after partial mesorectal excision. Histopathological records, standardized photographs and clinical records were assessed. The pathology and MRI findings were evaluated independently in a blinded fashion. RESULTS: MRI-detected residual mesorectum was identified in 54 (39·7 per cent) of 136 patients. There was agreement with the pathology findings in 88 patients (64·7 per cent). Residual mesorectum was more frequent in patients treated with partial mesorectal excision (63 per cent) than those who had total mesorectal excision (36 per cent) or abdominoperineal resection (13 per cent) (P < 0·001). Pathology and MRI findings both showed that the distal resection margin after partial mesorectal excision was less than 5 cm in more than three-quarters of patients, and less than 3 cm in more than one-third. CONCLUSION: Inadvertent residual mesorectum was commonly found on postoperative MRI, especially after partial mesorectal excision.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis: the Danish experience.

AIM: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with curative intent for selected patients with peritoneal carcinomatosis (PC). CRS and HIPEC have been implemented in Denmark at a single centre since 2006. Six years of data on these patients were analysed. METHOD: Patients with PC from colorectal or appendiceal cancer, pseudomyxoma peritonei or malignant peritoneal mesothelioma referred to the single national HIPEC centre were prospectively registered from June 2006 to July 2012. Morbidity, 30-day mortality and long-term survival of patients who underwent CRS and HIPEC were analysed. RESULTS: In total, 80 patients underwent CRS and HIPEC. PC originated from colorectal cancer in 34 patients, pseudomyxoma peritonei in 29, appendiceal cancer in 13 and malignant peritoneal mesothelioma in four patients. Thirty-two patients had one or more complications during the hospital stay. The 30-day mortality rate was 1.3%. The predicted 2-, 3- and 5-year survival was 60%, 47% and 38% in patients with PC from colorectal cancer, and 100%, 93% and 73% in pseudomyxoma peritonei patients. CONCLUSION: CRS and HIPEC is a safe procedure when centralized as in Denmark. Favourable long-term outcome was achieved in selected patients with PC from colorectal cancer and pseudomyxoma peritonei. Short-term and long-term outcomes were comparable to results from international centres.

Increased lymph node harvest from colorectal cancer resections using GEWF solution: a randomised study.

BACKGROUND: The lymph node harvest from colorectal specimens is pivotal for patients with colorectal cancer (CRC), independent of N stage. AIMS: To determine whether the use of GEWF solution (glacial acetic acid, ethanol, distilled water and formaldehyde) could improve the lymph node harvest in CRC specimens. METHODS: Consecutive fresh colonic (n = 60) and rectal (n = 60) specimens from patients with primary CRC resected at Aarhus University Hospital THG between March 2006 and July 2007 were randomised to either conventional preparation or GEWF preparation and examined in a standard manner. RESULTS: For colonic as well as rectal specimens, the GEWF solution increased the mean lymph node harvest from 9 and 10 to 16 and 17 lymph nodes per specimen compared to conventional prepared specimens (p<0.001). Using the recommended threshold of 12 lymph nodes to ensure adequacy of nodal harvest, the adequacy increased from less than half to almost three quarters independent of tumour origin (p<0.037). The proportion of node-negative specimens was not significantly different between the two preparation groups. CONCLUSION: The use of GEWF solution in patients with CRC significantly increases the lymph node harvest of resected specimens.