Oncological outcomes of laparoscopic versus open rectal cancer resections: meta-analysis of randomized clinical trials.

BACKGROUND: The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. METHODS: A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. RESULTS: Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. CONCLUSION: Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.

Intracorporeal vs extracorporeal anastomosis following neoplastic right hemicolectomy resection: a systematic review and meta-analysis of randomized control trials.

PURPOSE: While minimally invasive surgery is the preferred approach for right hemicolectomy, the choice of anastomotic technique is still debated. Both intracorporeal (ICA) and extracorporeal anastomosis (ECA) are described, with conflicting reports on safety and efficacy seen. This study aimed to examine impact of ICA and ECA on outcomes in right hemicolectomy. METHODS: A meta-analysis of randomized control trials (RCT) was performed. The primary outcome was overall morbidity. The secondary outcomes included both perioperative and post-operative outcomes. RESULTS: Four RCTs were included incorporating 399 patients (199 patients (49.9%) ICA Vs 200 (50.1%) ECA). There was no significant difference in overall morbidity (RR 0.79, 95% CI 0.43, 1.48, p = 0.47), anastomotic leak (RR 1.34, 95% CI 0.58, 3.13, p = 0.5) or surgical site infections (RR 0.53, 95% CI 0.17, 1.64, p = 0.27). ICA patients had a significantly less post-operative ileus (RR 0.53, 95% CI 0.3-0.94, p = 0.03) quicker return to first flatus (WMD - 0.71, 95% CI - 1.12, 0.31, p = 0.0005), first bowel motion (WMD - 0.53, 95% CI - 0.69, - 0.37, p < 0.00001) and first meal (WMD - 0.68, 95% CI - 1.33, - 0.03, p = 0.04). Pain scores were significantly better for ICA patients on POD 3 (WMD - 0.76, 95% CI - 1.23, - 0.28, p = 0.002), POD 4 (WMD - 0.90, 95% CI - 1.71, - 0.09, p = 0.03) and POD 5 (WMD - 0.67, 95% CI - 1.22, - 0.13, p = 0.01). Length of hospital stay was similar (WMD - 0.46, 95% CI - 1.14, 0.22, p = 0.19). CONCLUSION: ICA is associated with a quicker return to normal physiological function with equivalent post-operative morbidity. Both ECA and ICA are safe and feasible for restoring normal bowel continuity.

Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis.

BACKGROUND: Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta-analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. METHODS: The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age- and sex-matched cohorts. RESULTS: Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta-analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2  = 0 per cent). CONCLUSION: BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

ANTECEDENTES: Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20-40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA. MÉTODOS: Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo. RESULTADOS: No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80-1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)). CONCLUSIÓN: Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.

Clinicopathological features and oncological outcomes of patients with young-onset rectal cancer.

BACKGROUND: The incidence of rectal cancer among adults aged less than 50 years is rising. Survival data are limited and conflicting, and the oncological benefit of standard neoadjuvant and adjuvant therapies is unclear. METHODS: Disease-specific outcomes of patients diagnosed with rectal cancer undergoing surgical resection with curative intent between 2006 and 2016 were analysed. RESULTS: A total of 797 patients with rectal cancer were identified, of whom 685 had surgery with curative intent. Seventy patients were younger than 50 years and 615 were aged 50 years or more. Clinical stage did not differ between the two age groups. Patients aged less than 50 years were more likely to have microsatellite instability (9 versus 1·6 per cent; P = 0·003) and Lynch syndrome (7 versus 0 per cent; P < 0·001). Younger patients were also more likely to receive neoadjuvant chemoradiotherapy (67 versus 53·3 per cent; P = 0·003) and adjuvant chemotherapy (41 versus 24·2 per cent; P = 0·006). Five-year overall survival was better in those under 50 years old (80 versus 72 per cent; P = 0·013). The 5-year disease-free survival rate was 81 per cent in both age groups (P = 0·711). There were no significant differences in the development of locoregional recurrence or distant metastases. CONCLUSION: Despite accessing more treatment, young patients have disease-specific outcomes comparable to those of their older counterparts.

ANTECEDENTES: La incidencia de cáncer de recto entre adultos menores de 50 años está aumentando. Los datos de supervivencia son limitados y contradictorios, y el beneficio oncológico de los tratamientos neoadyuvantes y adyuvantes estándares no está claro. MÉTODOS: Se analizaron los resultados específicos relacionados con la enfermedad en pacientes diagnosticados de cáncer de recto operados con intención curativa entre 2006 y 2016. RESULTADOS: Se identificaron un total de 797 pacientes con cáncer de recto, de los cuales 685 fueron intervenidos quirúrgicamente con intención curativa. Setenta tenían menos de 50 años y 615 tenían 50 años o más. No hubo diferencias en el estadio clínico entre los dos grupos de edad. Los pacientes menores de 50 años tenían más probabilidades de tener inestabilidad de microsatélites (9% versus 2%, P = 0,003) y síndrome de Lynch (7% versus 0%, P ≤ 0,001). La supervivencia global a los 5 años fue mayor en los pacientes de menos de 50 años (80% y 72%; P = 0,013). La supervivencia libre de enfermedad a los 5 años fue del 81% en ambos grupos de edad (P = 0,711). No hubo diferencias significativas en el desarrollo de recidiva locorregional o metástasis a distancia. Los pacientes más jóvenes tenían más probabilidades de recibir quimiorradioterapia neoadyuvante (67% versus 53%, P = 0,003) y quimioterapia adyuvante (41% versus 24%, P = 0,006). CONCLUSIÓN: A pesar de tener acceso a más tratamientos, los pacientes jóvenes han presentado resultados específicos relacionados con la enfermedad comparables a sus homólogos de mayor edad.

Long-term functional results and quality of life after redo rectal surgery: delayed versus immediate colo-anal anastomosis.

AIM: To compare the functional results and quality of life after delayed colo-anal anastomosis (DCAA) or immediate colo-anal anastomosis (ICAA) following redo rectal surgery. METHOD: Twenty-six patients with DCAA between 2014 and 2018 were studied retrospectively (group A). Two control groups were used: 26 ICAA after redo surgery (group B) and 52 colo-anal anastomosis (CAA) after anterior resection (group C). Control groups were matched for age, sex, pelvic radiotherapy and time to surgery. Low Anterior Resection Syndrome (LARS) and Gastrointestinal Quality of Life Index (GIQLI) scores were used to assess function and quality of life. RESULTS: The indications for surgery were comparable for groups A and B: anastomotic failure with chronic sepsis (38% vs 50%, P = 0.40), vaginal fistula (42% vs 42%, P = 1) and urinary fistula (20% vs 8%, P = 0.22) as well as the number of previous abdominal operations (1.3 ± 0.9 vs 1.1 ± 0.6, P = 0.19). The median LARS score in the first 2 years was 30 [interquartile range (IQR) 14-41] for group A, 23 (IQR 0-41) for group B and 22 (IQR 11-37) for group C. After 2 years, the median LARS score improved in each group [A, 21 (IQR 11-35); B, 18 (IQR 5-26); C, 13 (IQR 9-20)], but was still high in group A. There was a tendency toward more major LARS in group A than in group B (46% vs 27%; P = 0.149). There was no difference in the mean GIQLI score between groups A and B (120 ± 16 vs 117 ± 19; P = 0.53) at the end of the follow-up period. Time after stoma closure (< 2 years) and previous radiotherapy were risk factors for major LARS in all populations. CONCLUSION: ICAA should be the procedure of choice where possible in redo surgery as it has better functional outcomes.

Systematic review and meta-analysis comparing primary resection and anastomosis versus Hartmann's procedure for the management of acute perforated diverticulitis with generalised peritonitis.

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.

Does transanal local resection increase morbidity for subsequent total mesorectal excision for early rectal cancer?

AIM: Local excision is recommended for early rectal cancer (pT1). Complementary total mesorectal excision (cTME) is warranted when bad pathological features are present. The impact of a prior local resection on the outcome remains unclear. The aim of this study was to assess if prior local excision increases the morbidity of a subsequent cTME compared with primary TME. METHODS: From 2001 to 2016 all patients who underwent TME after local excision for rectal adenocarcinoma were studied. All were matched (1:1) with patients who underwent primary TME, without neoadjuvant radiochemotherapy. The matching factors included age, sex, body mass index, American Society of Anesthesiologists score and type of surgery. Short-term morbidity and pathological examination of the resected specimen were compared. RESULTS: Forty-one patients were included (14 women, 34%, mean age 65 ± 11 years), comprising classic transanal excision (66%) and transanal endoscopic microsurgery (34%), and were matched to 41 patients who had primary TME. cTME was significantly longer (315 min ± 87 vs 275 min ± 58, P = 0.03). The overall morbidity was 48.8% in the local excision group vs 31.7% in the control group (P = 0.18). Surgical morbidity was 31.7% vs 26.8% (P = 0.8). Anastomotic related morbidity was similar (local excision 17% vs TME 14.6%, P = 0.84) and the mean length of stay was similar (14 days) in both groups. There was a tendency to a worse quality of mesorectal excision in the cTME group (17% vs 5%, P = 0.15). CONCLUSION: Local excision prior to TME for early rectal cancer tends to increase overall morbidity and may worsen the quality of the mesorectal plane but should be considered as a surgical approach in select cases.

Minimally invasive approaches to the management of anastomotic leakage following restorative rectal cancer resection.

AIM: Management of anastomotic leakage (AL) following rectal resection has evolved with increasing use of less invasive techniques. The aim of this study was to review the management of AL following restorative rectal cancer resection in a tertiary referral centre. METHOD: A retrospective review of a prospectively maintained database was performed. The primary outcome was successful management of AL. The secondary outcome was the impact of AL on oncological outcome. RESULTS: Five hundred and two restorative rectal cancer resections were performed during the study period. The incidence of AL was 9.9% (n = 50). AL occurred more commonly following neoadjuvant chemoradiotherapy (n = 31/252, 12.3%) than in those who did not receive neoadjuvant chemoradiotherapy (n = 19/250, 7.6%; P = 0.107); however, this was not statistically significant. Successful minimally invasive drainage was achieved in 28 patients (56%, radiological n = 24, surgical n = 4). Trans-rectal drainage was the most common drainage method (n = 14). The median duration of drainage was longer in the neoadjuvant group (27 vs 18 days). Surgical intervention was required in 11 patients, with anastomotic takedown and end-colostomy formation was most commonly required. Successful management of AL with drainage (maintenance of the anastomosis without the need for further intervention) was achieved in 26 of the 28 patients. There were no significant differences in overall or disease-free survival when patients with AL were compared with patients without AL (69.4% vs 72.6%, P = 0.99 and 78.7% vs 71.3%, P = 0.45, respectively). CONCLUSION: In selected patients, AL following restorative rectal resection can be effectively controlled using minimally invasive radiological or surgical drainage without the need for further intervention.

Prognostic value and characteristics of N1c colorectal cancer.

AIM: The presence of tumour deposits (TDs) in colorectal cancer (CRC) is associated with poor prognosis. The seventh edition of TNM subclassified a new nodal stage, N1c, characterized by the presence of TDs without any concurrent positive lymph node (LN). It is not clear if the N1c category is or is not equal to LN metastasis. We aimed to examine the prevalence, characteristics and prognostic significance of this new subcategory. METHOD: Consecutive patients who underwent surgery for CRC in two centres (2011-2014) were analysed. N1 cM0 patients were matched against non-N1 cM0 (N0, N1a and N1b) patients for 3-year overall survival (OS) and disease-free survival (DFS). RESULTS: We identified 1122 patients with 648 (57.8%) colonic cancers. In 57 patients (5.1%), N1c status was associated with rectal cancers [rectum = 33/57 (57.9%) vs colon = 24/57 (42.1%); P = 0.029], a higher pathological tumour stage [pT3-T4 N1c = 55/843 (6.5% vspT3-T4 non-N1c = 2/279 (0.7%); P < 0.0001] and vascular emboli [n = 35 (61.4%) vs n = 552 (51.8%); P = 0.0305]. Synchronous metastasis was observed in 23 cases (40%). After a mean follow-up of 31 months, 3-year OS for M0 patients, was 89.4%, 89.1%, 86.6% and 81.8% for N0, N1a, N1b and N1c tumours, respectively. DFS was significantly worse for N1c than for N0 (P = 0.0169), with N1c status having a significant effect on DFS in colonic cancers (P = 0.014). The presence of more than one TD was associated with a significantly worse DFS (P = 0.021). CONCLUSION: Our results indicate that N1c CRC patients should be included among high-risk patients for whom it is widely accepted that adjuvant chemotherapy should be considered.

Organ preservation with local excision or active surveillance following chemoradiotherapy for rectal cancer.

BACKGROUND: Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality, and to improve functional outcome. METHODS: Locally advanced non-metastatic rectal cancers were identified from a prospective database. Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy (CRT) (50-54 Gy and 5-fluorouracil), and were reassessed 6-8 weeks post treatment. An active surveillance programme ('watch and wait') was offered to patients who were found to have a complete endoluminal response. Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm. Patients were followed up clinically, endoscopically and radiologically to assess for local recurrence or disease progression. RESULTS: Of 785 patients with rectal cancer between 2005 and 2015, 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT. Sixty out of three hundred and sixty-two (16.5%) patients were treated with organ-preserving strategies - 10 with 'watch and wait' and 50 by transanal excision. Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings. There was no significant difference in overall survival (85.6% vs 93.3%, P=0.414) or disease-free survival rate (78.3% vs 80%, P=0.846) when the outcomes of radical surgery were compared with organ preservation. Tumour regrowth occurred in 4 out of 45 (8.9%) patients who had organ preservation. CONCLUSIONS: Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT. Transanal excision defines the pathological response and refines decision-making.

Meta-analysis of the impact of surgical approach on the grade of mesorectal excision in rectal cancer.

BACKGROUND: The subspecialization of colorectal surgeons, and improvements in the quality of mesorectal excision have revolutionized rectal cancer surgery. With the increasing use of minimally invasive techniques, the completeness of the mesorectal excision has been questioned. This study aimed to assess the pathological outcomes of open versus laparoscopic rectal resection. METHODS: A meta-analysis of RCTs was undertaken. The primary endpoint was the adequacy of the mesorectal excision. Secondary endpoints included circumferential resection margin and distance to resection margins. RESULTS: Four studies were included, reporting on 2319 patients; 972 (41·9 per cent) had open and 1347 (58·1 per cent) had laparoscopic resections. Meta-analysis of adequacy of the mesorectal excision showed a small difference in achieving an intact mesorectum in favour of open surgery (risk ratio (RR) 1·06, 95 per cent c.i. 1·02 to 1·10; P = 0·001). Superficial defects were more common in laparoscopic surgery (RR 0·70, 0·54 to 0·89; P = 0·004). Deep mesorectal defects (RR 0·78, 0·51 to 1·20; P = 0·256), circumferential margin (CRM) positivity (RR 0·85, 0·62 to 1·16; P = 0·310), and distance to radial (mean difference (MD) -0·06, 95 per cent c.i. -0·10 to 0·23; P = 0·443) and distal (MD 0·03, -0·06 to 0·12; P = 0·497) margins were all similar. A complete resection (intact mesorectum, negative CRM and distal margin) was achieved in 350 of 478 patients (73·2 per cent) in the laparoscopic group and 372 of 457 (81·4 per cent) in the open group (risk difference (RD) 8 (95 per cent c.i. 3 to 13) per cent; P = 0·003). However, an acceptable mesorectum (intact or superficial defects only) was present in 1254 of 1308 (95·9 per cent) and 916 of 949 (96·5 per cent) in the laparoscopic and open groups respectively (RD 1 (-1 to 3) per cent; P = 0·263). CONCLUSION: Small differences in mesorectal quality were evident between open and laparoscopic rectal resections. This may be attributable to use of laparoscopic instruments; however, to date minor defects have not affected oncological outcomes.

The management of perineal hernia following abdomino-perineal excision for cancer.

PURPOSE: Perineal hernia (PH) is a tardive complication following abdomino-perineal resection (APR). Many repair methods are described and evidences are lacking. The aim of this study was to report PH management, analyze surgery outcomes and review the available literature. METHODS: We retrospectively included all consecutive PH repair after APR performed between 2001 and 2017. We recorded data on APR surgery, PH symptoms and repair, and follow-up (recurrence and morbidity). Literature review included published articles on PubMed between 1960 and 2017. RESULTS: 24 PH repairs were included. The approach was perineal N = 16, abdominal N = 5 and combined N = 3. A biological mesh was used for 17, a synthetic for 5 and a flap for 2 patients. The median follow-up was 25 months. Overall morbidity was 37.5% (N = 9): 37.5% for the perineal, 20% for the abdominal, and 66.7% for the combined approach. Complications occurred in 35.3% of biological and 20% of synthetic mesh repairs. Recurrence rate was 41.7%, similar for biological (n = 8, 47.1%) and synthetic meshs (n = 2; 40%). No recurrence occurred in the flap group. Depending of the approach, we found 50% for perineal (n = 8) and 40% of the abdominal cohort (N = 2). Among twelve studies, recurrence rates ranged from 0 to 66.7%. Abdominal or laparoscopic approach with synthetic mesh was associated with less recurrences (0 and 12.5% respectively) and complications (37.5% and 9.5%). CONCLUSIONS: Recurrences following PH repair are high irrespective of the repair technique. More studies are necessary to identify PH risk factors and decide the appropriate perineal reconstruction.

Effects of CDX2 on prognosis and chemotherapy responsiveness in mismatch repair-deficient colorectal cancer.

BACKGROUND: Caudal-related homeobox transcription factor 2 (CDX2) is an intestine-specific transcription factor implicated in tumour differentiation, proliferation, cell adhesion and migration. Negative CDX2 status (CDX2-) is associated with worse prognosis in colorectal cancer and may identify high-risk stage II disease that benefits from adjuvant chemotherapy. This observational study investigated whether CDX2- is associated with prognosis or response to chemotherapy in the mismatch repair-deficient (dMMR) phenotype of colorectal cancer. METHODS: Patients with resectable dMMR colorectal cancer were eligible for inclusion. The prognostic and predictive value of CDX2 expression on the presence of lymph node metastasis (LNM) and survival was investigated. CDX2 status was determined via immunohistochemistry using the Leica Bond™ CDX2 (clone EP25) ready-to-use primary antibody. RESULTS: Some 235 of 238 consecutive dMMR tumours were assessed for CDX2 status. CDX2- was observed in 15·7 per cent of colorectal cancer. Interobserver agreement was excellent (κ = 0·863; P < 0·001). CDX2- was significantly associated with female sex, increased size, advanced stage, worse conventional and poorly differentiated cluster (PDC) grade, mucinous morphology, perineural and lymphovascular invasion, and pN status (all P ≤ 0·038). CDX2- was not associated with LNM or survival in multivariable analysis. Independent predictors of LNM were PDC grade (odds ratio (OR) 4·12, 95 per cent c.i. 1·76 to 9·63; P = 0·001) and extramural venous invasion (OR 3·79, 1·62 to 8·85; P = 0·002). Budding (hazard ratio (HR) 2·79, 95 per cent c.i. 1·60 to 4·87; P < 0·001), pT status (HR 3·59, 1·29 to 10·01; P = 0·015) and adjuvant chemotherapy (HR 2·07, 1·15 to 3·74; P = 0·016) were independently associated with worse disease-free survival. CONCLUSION: CDX2- does not confer a worse prognosis in the dMMR phenotype of colorectal cancer. The MMR status of patients with colorectal cancer should be determined before assessing CDX2 status.

The current value of determining the mismatch repair status of colorectal cancer: A rationale for routine testing.

Colorectal Cancer (CRC) is the third most prevalent cancer in men and women. Up to 15% of CRCs display microsatellite instability (MSI). MSI is reflective of a deficient mismatch repair (MMR) system and is most commonly caused by hypermethylation of the MLH1 promoter. However, it may also be due to autosomal dominant constitutional mutations in DNA MMR, termed Lynch Syndrome. MSI may be diagnosed via polymerase chain reaction (PCR) or alternatively, immunohistochemistry (IHC) can identify MMR deficiency (dMMR). Many institutions now advocate universal tumor screening of CRC via either PCR for MSI or IHC for dMMR to guide Lynch Syndrome testing. The association of sporadic MSI with methylation of the MLH1 promoter and an activating BRAF mutation may offer further exclusion criteria for genetic testing. Aside from screening for Lynch syndrome, MMR testing is important because of its prognostic and therapeutic implications. Several studies have shown MSI CRCs exhibit different clinicopathological features and prognosis compared to microsatellite-stable (MSS) CRCs. For example, response to conventional chemotherapy has been reported to be less in MSI tumours. More recently, MSI tumours have been shown to be responsive to immune-checkpoint inhibition providing a novel therapeutic strategy. This provides a rationale for routine testing for MSI or dMMR in CRC.