Danish Colorectal Cancer Group Database Research Articles

The Association of Mismatch Repair Status with Microscopically Positive (R1) Margins in Stage III Colorectal Cancer: A Retrospective Cohort Study

BackgroundThere is mounting evidence that microscopically positive (R1) margins in patients with colorectal cancer (CRC) may represent a surrogate for aggressive cancer biology rather than technical failure during surgery. However, whether detectable biological differences exist between CRC with R0 and R1 margins is unknown. We sought to investigate whether mismatch repair (MMR) status differs between Stage III CRC with R0 or R1 margins.MethodsPatients treated for Stage III CRC from January 1, 2016 to December 31, 2019 were identified by using the Danish Colorectal Cancer Group database. Patients were stratified according to MMR status (proficient [pMMR] vs. deficient [dMMR]) and margin status. Outcomes of interest included the R1 rate according to MMR and overall survival.ResultsA total of 3636 patients were included, of whom 473 (13.0%) had dMMR colorectal cancers. Patients with dMMR cancers were more likely to be elderly, female, and have right-sided cancers. R1 margins were significantly more common in patients with dMMR cancers (20.5% vs. 15.2%, p < 0.001), with the greatest difference seen in the rate of R1 margins related to the primary tumour (8.9% vs. 4.7%) rather than to lymph node metastases (11.6% vs. 10.5%). This association was seen in both right- and left-sided cancers. On multivariable analyses, R1 margins, but not MMR status, were associated with poorer survival, alongside age, pN stage, perineural invasion, and extramural venous invasion.ConclusionsIn patients with Stage III CRC, dMMR status is associated with increased risks of R1 margins following potentially curative surgery, supporting the use of neoadjuvant immunotherapy in this patient group.

Current treatment of pT1 rectal cancers in Denmark: Aretrospective national cohort study.

Organ preservation strategies for patients with rectal cancer are increasingly common. In appropriately selected patients, local excision (LE) of pT1 cancers can reduce morbidity without compromising cancer-related outcomes. However, determining the need for completion surgery after LE can be challenging, and it is unknown if prior LE compromises subsequent total mesorectal excision (TME). The aim of this study is to describe the current management of patients with pT1 rectal cancers. This is a retrospective national cohort study of the Danish Colorectal Cancer Group database, including patients with newly diagnosed pT1 cancers between 2016 and 2020. Patients were stratified according to treatment into LE alone, completion TME after LE or upfront TME. The treatment and outcomes of these groups were compared. A total of 1056 patients were included. Initial LE was performed in 715 patients (67.7%), of whom 194 underwent completion TME (27.1%). The remaining 341 patients underwent upfront TME (32.3%). Patients undergoing LE alone were more likely to be male with low rectal cancers and greater comorbidity. No differences in specimen quality or perioperative outcomes were noted between patients undergoing completion or upfront TME. Eighty-five patients (15.9%) had lymph node metastases (LNM). Pathological risk factors poorly discriminated between patients with and without LNM, with similar rates seen in patients with zero (14.1%), one (12.0%) or two (14.4%) risk factors. LE is a key component of the treatment of pT1 rectal cancer and does not appear to affect the outcomes of completion TME. Patient selection for completion TME remains a major challenge, with current stratification methods appearing to be inadequate.

Incidence of Recurrence and Time to Recurrence in Stage I to III Colorectal Cancer

Management of colorectal cancer (CRC) has been updated continuously over the past 2 decades. While the combination of these initiatives has had implications for improved survival, the implications for rates of recurrence remain unexplored. To ascertain the rates of recurrence and describe time to recurrence within 5 years of surgery with curative intent for stages I to III CRC. This cohort study used the Danish Colorectal Cancer Group Database to identify patients with Union for International Cancer Control (UICC) stages I to III CRC who underwent primary surgery between January 1, 2004, and December 31, 2019. They were followed up until recurrence (event), death (competing event), diagnosis of a second cancer (competing event), emigration (censoring event), 5 years postoperatively (censoring event), or January 1, 2023 (censoring event), whichever came first. Recurrence status was ascertained through individual-level linked data from the Danish Cancer Registry, Danish National Patient Registry, and Danish Pathology Registry using a validated algorithm. Data were analyzed from January 1 to August 8, 2023. Primary surgery performed during 3 calendar periods (2004-2008, 2009-2013, and 2014-2019) stratified by tumor site (colon or rectum) and UICC stage (I, II, and III). Stage-specific 5-year recurrence reported as the cumulative incidence function (CIF) of recurrence, the association between calendar period of primary surgery and recurrence risk reported as subdistribution hazard ratios (sHRs), and the time from surgery to recurrence. Of the 34 166 patients with UICC stages I to III CRC (median [IQR] age, 70 [62-77] years); 18 552 males [54.3%]) included in the study, 7027 developed recurrence within 5 years after the primary surgery. For colon cancer, the 5-year CIF of recurrence decreased over the 3 calendar periods from 16.3% to 6.8% for UICC stage I, from 21.9% to 11.6% for UICC stage II, and from 35.3% to 24.6% for UICC stage III colon cancer. For rectal cancer, the 5-year CIF decreased over the 3 periods from 19.9% to 9.5% for stage I, from 25.8% to 18.4% for stage II, and from 38.7% to 28.8% for stage III disease. Patients with stage III disease had a shorter time from surgery to recurrence compared with those with stage I disease (time ratio stage III vs stage I = 0.30; 95% CI, 0.28-0.32). Cancers detected through screening were associated with lower stage-adjusted risks of recurrence (sHR, 0.81; 95% CI, 0.73-0.91) compared with cancers not detected through screening. In this cohort of patients with CRC, the risk of recurrence decreased in patients with stages I to III disease during the study period. Cancer detection by screening was associated with an even lower risk of recurrence. Time to recurrence differed according to UICC stage. Because the risk of recurrence was so low in selected patient groups, future research is warranted to explore risk-stratified surveillance protocols in patients with CRC.

Robotic versus laparoscopic approach for left-sided colon cancer: a nationwide cohort study.

The use of robot-assisted surgery for left-sided colon cancer is increasing in Denmark; however, it is yet to be established if the robotic approach results in improved clinical outcomes compared with the corresponding laparoscopic approach. The aim of this study was to compare the intraoperative and short-term postoperative outcomes of robot-assisted surgery with laparoscopic surgery for left-sided colon cancer at a national level. The study is a nationwide database study based on data from the Danish Colorectal Cancer Group database. Patients from all colorectal centres in Denmark treated with surgery with curative intent in an elective setting with either robotic or laparoscopic left colectomy or sigmoidectomy during the period 2014-2019 were included. To adjust for confounding, propensity score matching (PSM) was performed and the groups were compared for age, sex, body mass index, American Society of Anesthesiologists classification, performance score, year of diagnosis, neoadjuvant chemotherapy, left colectomy or sigmoidectomy, tumour localization, use of stoma or stenting and pathological T (pT) category. A total of 5532 patients were available for analysis, and after PSM in a ratio of 2:1, 1392 laparoscopic and 696 robotic cases were identified. After matching we found a lower conversion rate and a higher lymph node yield in the robotic group compared with the laparoscopic group (5.8% vs. 11%, p < 0.001 and 27 vs. 24, p < 0.001, respectively). Further, we found a higher proportion of patients with a lymph node yield of 12 or more in the robotic group (97% vs. 94.8%, p = 0.02). Plane of dissection, radicality and pathological disease stages did not differ between the two groups. We found no difference in either overall surgical (13% vs. 11.1%, p = 0.23) or medical (5.6% vs. 6.5%, p = 0.49) postoperative complications and no difference in 30-day (p = 0.369) or 90-day mortality (p = 0.08). Robot-assisted surgery for left-sided colon cancer was associated with a significantly lower conversion rate and a significantly higher lymph node yield than the laparoscopic approach. Postoperative morbidity and mortality were similar in the two groups.

Less Invasive Primary Treatment for Colorectal Cancer After Implementation of National Screening: A Nationwide Cohort Study.

The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program. This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index. The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC: n = 636 vs. NSD-CRC: n = 334, RR: 2.50, P < 0.001), (robotic-assisted) laparoscopic resection ((n = 616 vs. n = 773, RR: 1.27, P < 0.001), n = 2759 vs. n = 3471, RR: 1.11, P < 0.001), and radical resection (n = 3890 vs. n = 4834, RR: 1.02, P = 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (n = 32 vs. n = 562, RR: 0.09, P < 0.001), open surgery (n = 391 vs. n = 1410, RR: 0.53, P < 0.001), supplementary organ resection (n = 259 vs. n = 860, RR: 0.56, P < 0.001), and stoma formation (n = 526 vs. n = 1040, RR: 0.89, P = 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC: n = 262, NSD-CRC: n = 994, RR: 1.43, P < 0.001). SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC.

Uneven Between-Hospital Distribution of Patient-Related Risk Factors for Adverse Outcomes of Colorectal Cancer Treatment: A Population-Based Register Study.

The purpose of this study was to elucidate between-hospital variation in the prevalence at the time of diagnosis of patient-related risk factors for adverse outcomes of colorectal cancer (CRC) treatment. A register-based national cohort of 44,471 patients diagnosed with CRC and registered in the Danish Colorectal Cancer Group database in 2009-2018 was included in the study. Patient-related risk factors present at diagnosis were collected from national Danish registers within the areas of demography, lifestyle factors, comorbidity, participation in screening, disease-related factors and socioeconomic factors. Prediction models of short-term postoperative outcomes and mortality were modelled to examine the potential aggregated impact of patient-related risk factors on outcomes, and variations between hospitals were examined. The most conspicuous variations found were for old age (75+ years), ranging from 31% (95% confidence interval (95% CI): 29-33%) to 46% (95% CI: 43-48%), Union for International Cancer Control Stage I ranging from 12% (95% CI: 10-14%) to 21% (95% CI: 19-22%), Stage IV ranging from 23% (95% CI: 21-25%) to 35% (95% CI: 34-37%) and American Society of Anesthesiologists score ≥III ranging from 18% (95% CI: 16-19%) to 40% (95% CI: 37-43%). Clinically significant variations were found in predicted probability of 30-day surgical complications which varied from 17% (95% CI: 16-17%) to 23% (95% CI: 22-23%) and 90-day postoperative mortality which varied between 3.2% (95% CI: 3-3.4%) and 5.5% (95% CI: 4.9-6%). Marked variation in the prevalence of patient-related risk factors for adverse outcomes of colorectal cancer treatment exists between hospitals in Denmark. It seems reasonable to take these differences into account when comparing outcomes between hospitals.

Identifying Recurrences Among Non-Metastatic Colorectal Cancer Patients Using National Health Data Registries: Validation and Optimization of a Registry-Based Algorithm in a Modern Danish Cohort.

Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR). We ascertained data on 1129 patients operated for UICC TNM stage I-III CRC during 2012-2017 registered in the CRC biobank at the Department of Molecular Medicine, Aarhus University Hospital, Denmark. Individual-level data were linked with data from the Danish Colorectal Cancer Group database, Danish Cancer Registry, Danish National Registry of Patients, and Danish Pathology Registry. The algorithm identified recurrence based on diagnosis codes of local recurrence or metastases, the receipt of chemotherapy, or a pathological tissue assessment code of recurrence more than 180 days after CRC surgery. A subgroup was selected for validation of the algorithm using medical record reviews as a reference standard. We found a 3-year cumulative recurrence rate of 20% (95% CI: 17-22%). Manual medical record review identified 80 recurrences in the validation cohort of 522 patients. The algorithm detected recurrence with 94% sensitivity (75/80; 95% CI: 86-98%) and 98% specificity (431/442; 95% CI: 96-99%). The positive and negative predictive values of the algorithm were 87% (95% CI: 78-93%) and 99% (95% CI: 97-100%), respectively. The median difference in TTR (TTRMedical_chart-TTRalgorithm) was -8 days (IQR: -21 to +3 days). Restricting the algorithm to chemotherapy codes from oncology departments increased the positive predictive value from 87% to 94% without changing the negative predictive value (99%). The algorithm detected recurrence and TTR with high precision in this contemporary cohort. Restriction to chemotherapy codes from oncology departments using department classifications improves the algorithm. The algorithm is suitable for use in future observational studies.

Outcomes of emergency surgical interventions in right-sided colonic cancer: nationwide population-based study based on Danish Colorectal Cancer Group register.

The aim of this study was to investigate the trends in morbidity and mortality of patients with right-sided colonic cancer who had an emergency surgical procedure in Denmark after the introduction of quality index parameters. This was a retrospective nationwide study based on a prospectively maintained Danish Colorectal Cancer Group database focused on right-sided colonic cancer in the interval from 1 May 2001 to 30 April 2018, who underwent emergency surgical intervention (within 48 h of hospital admission). The primary objective was to investigate the trends in morbidity and mortality throughout the study years. Multivariable estimates were adjusted for age, sex, smoking status, alcohol consumption, ASA score classification, tumour localization, type of access to abdominal cavity, surgeon's grade of specialization, and metastatic disease. Out of 2839 patients, a total of 2740 patients fulfilled the inclusion criteria, of whom 2464 underwent right or transverse colon resection (89.9 per cent). The 30-day and 90-day postoperative mortality rates were significantly reduced over the time of the study (OR 0.943, 95 per cent c.i. 0.922 to 0.965, P < 0.001 and OR 0.953, 95 per cent c.i. 0.934 to 0.972, P < 0.001 respectively); however, the complication rates did not follow this trend. Older patients (OR 1.032, 95 per cent c.i. 1.009 to 1.055, P = 0.005) and patients with high ASA scores (OR 1.61, 95 per cent c.i. 1.422 to 1.830, P < 0.001) had higher rates of severe grade 3b postoperative complications. A stoma was constructed in 276 patients (10 per cent), whereas a stent was used in only eight patients. Defunctioning procedures, including stoma construction or colonic stenting (without oncological resection), did not reduce the risk of complications compared with that of definitive surgery. The 30-day and 90-day postoperative mortality rates were significantly reduced over the time of the study. Age and ASA score were risk factors for severe postoperative complications.

Diet and bowel symptoms among colon cancer survivors

Background Survival from colon cancer (CC) has improved considerably over the last decades, yet many survivors suffer from late sequelae from treatment. Typical symptoms of bowel dysfunction after treatment of CC are diarrhea, urge for defecation, fecal incontinence, bloating and constipation. Most CC survivors make dietary changes to alleviate bowel symptoms. We aimed to describe the self-perceived effects of diet on bowel function among CC survivors and the level of dietary information given. Materials and methods In this cross-sectional study, CC patients from four surgical departments in Denmark completed surveys regarding the effects of diet on their bowel function and whether they had previously received dietary advice. Data concerning sociodemographic characteristics and the surgical procedure (right-sided or left-sided hemicolectomy) were collected from the Danish Colorectal Cancer Group database. Forty-four healthcare professionals specialized in CC completed a questionnaire on how they advise CC. Descriptive statistics were applied. Results Among 1544 patients invited, 1239 (80.4%) responded, and 844 met the inclusion criteria (53% males, median age 72.6 years, median time since surgery 742 days). Among these, 267 (32%) reported that food affected bowel function. Fat was perceived to have a negative effect in 193 (25%), spices in 149 (19%), sweets in 101 (13%) and meat in 99 (13%). There was no association between tumor site and food categories affecting bowel function (p = 0.078). Most healthcare professionals (93%) stated that their unit gave advice about diet, but only 24% of patients remembered such information. Conclusion One-third of CC survivors perceive that food items, especially fat and spices have a negative impact on their bowel function. We found a major discrepancy between healthcare professionals reporting that they provide advice and the proportion of patients remembering this. There is an unmet need for further recognition of the role of diet in CC rehabilitation and for intervention studies of treatment principles.

Developing prediction models for short-term mortality after surgery for colorectal cancer using a Danish national quality assurance database.

The majority of colorectal cancer surgeries are performed electively, and treatment is often decided at the multidisciplinary team conference. Although the average 30-day mortality rate is low, there is substantial population heterogeneity from young, healthy patients to frail, elderly patients. The individual risk of surgery can vary widely, and tailoring treatment for colorectal cancer may lead to better outcomes. This requires prediction of risk that is accurate and available prior to surgery. Data from the Danish Colorectal Cancer Group database was transformed into the Observational Medical Outcomes Partnership Common Data Model. Models were developed to predict the risk of mortality within 30, 90, and 180days after colorectal cancer surgery using only covariates decided at the multidisciplinary team conference. Several machine-learning models were trained, but due to superior performance, a Least Absolute Shrinkage and Selection Operator logistic regression was used for the final model. Performance was assessed with discrimination (area under the receiver operating characteristic and precision recall curve) and calibration measures (calibration in large, intercept, slope, and Brier score). The cohort contained 65,612 patients operated for colorectal cancer in the period from 2001 to 2019 in Denmark. The Least Absolute Shrinkage and Selection Operator model showed an area under the receiver operating characteristic for 30-, 90-, and 180-day mortality after colorectal cancer surgery of 0.871 (95% CI: 0.86-0.882), 0.874 (95% CI: 0.864-0.882), and 0.876 (95% CI: 0.867-0.883) and calibration in large of 1.01, 0.98, and 1.01, respectively. The postoperative short-term mortality prediction model showed excellent discrimination and calibration using only preoperatively known predictors.

Epidural analgesia and postoperative complications in colorectal cancer surgery. An observational registry-based study.

BackgroundIn colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery.MethodsWe identified patients undergoing colorectal cancer surgery 2008–2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications.ResultsWe identified 19 932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87–1.04).ConclusionIn total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.

Training prediction models for individual risk assessment of postoperative complications after surgery for colorectal cancer.

The occurrence of postoperative complications and anastomotic leakage are major drivers of mortality in the immediate phase after colorectal cancer surgery. We trained prediction models for calculating patients' individual risk of complications based only on preoperatively available data in a multidisciplinary team setting. Knowing prior to surgery the probability of developing a complication could aid in improving informed decision-making by surgeon and patient and individualize surgical treatment trajectories. All patients over 18years of age undergoing any resection for colorectal cancer between January 1, 2014 and December 31, 2019 from the nationwide Danish Colorectal Cancer Group database were included. Data from the database were converted into Observational Medical Outcomes Partnership Common Data Model maintained by the Observation Health Data Science and Informatics initiative. Multiple machine learning models were trained to predict postoperative complications of Clavien-Dindo grade ≥ 3B and anastomotic leakage within 30days after surgery. Between 2014 and 2019, 23,907 patients underwent resection for colorectal cancer in Denmark. A Clavien-Dindo complication grade ≥ 3B occurred in 2,958 patients (12.4%). Of 17,190 patients that received an anastomosis, 929 experienced anastomotic leakage (5.4%). Among the compared machine learning models, Lasso Logistic Regression performed best. The predictive model for complications had an area under the receiver operating characteristic curve (AUROC) of 0.704 (95%CI 0.683-0.724) and an AUROC of 0.690 (95%CI 0.655-0.724) for anastomotic leakage. The prediction of postoperative complications based only on preoperative variables using a national quality assurance colorectal cancer database shows promise for calculating patient's individual risk. Future work will focus on assessing the value of adding laboratory parameters and drug exposure as candidate predictors. Furthermore, we plan to assess the external validity of our proposed model.

Inhalation anaesthesia compared with total intravenous anaesthesia and postoperative complications in colorectal cancer surgery: an observational registry-based study†

BackgroundPostoperative complications are common after colorectal surgery, and possibly related to the type of anaesthesia. We aimed to determine associations between the type of anaesthesia and complications after colorectal cancer surgery using Danish registries. MethodsPatients undergoing colorectal cancer surgery (2004–18) were identified in the Danish Colorectal Cancer Group Database. The cohort was enriched with the Danish Anaesthesia Database and Danish National Prescription Registry data linked by Danish Central Person Registration number. Patients were classified according to type of general anaesthesia: inhalation or TIVA. Confounders were adjusted by propensity score matching. The primary outcome was complications within 30 days postoperatively. Secondarily, we assessed specific medical and surgical complications. ResultsWe identified 22 179 individuals undergoing colorectal cancer surgery with accompanying anaesthesia data. Propensity score matching yielded 8722 individuals per group. After propensity score matching, postoperative complications were seen in 1933 (22.2%) patients undergoing inhalation anaesthesia and in 2199 (25.2%) undergoing TIVA (odds ratio [OR]=0.84; 95% confidence interval [CI], 0.79–0.91). Although no difference was observed for medical complications, 1369 (15.7%) undergoing inhalation anaesthesia had surgical complications compared with 1708 (19.6%) undergoing TIVA (OR=0.76; 95% CI, 0.71–0.83). Rates of wound dehiscence, anastomotic leak, ileus, wound abscess, intra-abdominal abscess, and sepsis were statistically significantly lower in the inhalation anaesthesia group. ConclusionIn this propensity score-matched registry study, use of inhalation anaesthesia was associated with fewer postoperative complications after colorectal cancer surgery than use of TIVA. Inhalation anaesthesia was associated with fewer complications related to wound healing and surgical infections.

Neoadjuvant chemotherapy in patients undergoing colonic resection for locally advanced nonmetastatic colon cancer: Anationwide propensity score matched cohort study.

Neoadjuvant chemotherapy (NCT) for nonmetastatic colon cancer is not routinely used, and is currently only recommended as a treatment option for a subgroup of patients with T4b colon cancers in clinical guidelines. However, NCT may cause downstaging of the tumour, increase resectability, eradicate micrometastases and thereby improve long-term outcomes for patients with nonmetastatic colon cancer. The aim of this study was to investigate the short-term postoperative outcomes in a nationwide cohort of patients with locally advanced colon cancer (LACC) receiving NCT. Using the Danish Colorectal Cancer Group Database, data were retrieved on patients diagnosed with LACC (defined as clinical T3 with extramural tumour invasion >5mm or T4) and treated with resection with a curative intent between 2015 and 2019. Propensity score matching (PSM) in a 1:1 ratio was performed to compare short-term surgical and oncological outcomes in patients receiving NCT with patients operated on without receiving NCT. A total of 179 LACC patients were treated with NCT and 1131 were not. After PSM, 145 patients remained in each group. We found no significant differences in any short-term postoperative outcomes between the two groups. We found significant differences in favour of NCT regarding radicality and pathological N category [86% vs. 81% R0 (P=0.029) and 51% vs. 46% pN0 (P=0.017), respectively]. Neoadjuvant chemotherapy for LACC does not result in worse short-term postoperative outcomes and may increase the R0 rate as well as node-negative disease. Results on long-term benefits including survival are awaited from several ongoing randomized controlled trials.

Anastomosis technique and leakage rates in minimally invasive surgery for right-sided colon cancer. A retrospective national cohort study.

The aim of this study was to describe the different techniques currently used in Denmark to construct right-sided ileocolic anastomoses in minimally invasive surgery, and investigate, compare and analyse the anastomotic configurations and their anastomotic leakage (AL) rates. This was a retrospective register-based, study design using prospectively collected data from the Danish Colorectal Cancer Group (DCCG) database. All patients aged 18years or older with a malignant colorectal tumour in Denmark in the period of 1 February 2015 until 31 December 2019, and who had an elective, curative, minimally invasive right hemicolectomy (MIRH) with ileocolic anastomosis, were included. Three thousand three hundred ninety-eight patients were included. The most commonly used anastomotic approach was the extracorporeal (EC) hand-sewn anastomosis (HA) with end-to-end configuration (59%) and the second most used was the EC stapled anastomosis (SA) side-to-side configuration (20%). The latter had a higher AL rate compared with the hand-sewn technique (3.8% vs. 1.3%), and had significantly higher odds ratio (OR) (OR: 2.85, 95% CI: 1.56-4.92, p < 0.0001) for AL in the adjusted regression model. The least used technique was the end-to-side HA which also had a significantly higher OR (OR: 3.05, 95% CI: 1.30-7.15, p = 0.010) compared with the end-to-end HA. Smoking was an independent factor associated with higher OR for AL. The ileocolic end-to-end HA was the most commonly used technique and had the lowest AL rate in MIRH for colon cancer. The EC SA technique and tobacco smoking were independent risk factors for leakage of the ileocolic anastomosis.

Epidural Analgesia and Recurrence after Colorectal Cancer Surgery: A Danish Retrospective Registry-based Cohort Study.

Surgery is the main curative treatment for colorectal cancer. Yet the immunologic and humoral response to surgery may facilitate progression of micro-metastases. It has been suggested that epidural analgesia preserves immune competency and prevents metastasis formation. Hence, the authors tested the hypothesis that epidural analgesia would result in less cancer recurrence after colorectal cancer surgery. The Danish Colorectal Cancer Group Database and the Danish Anesthesia Database were used to identify patients operated for colorectal cancer between 2004 and 2018 with no residual tumor tissue left after surgery. The exposure group was defined by preoperative insertion of an epidural catheter for analgesia. The primary outcome was colorectal cancer recurrence, and the secondary outcome was mortality. Recurrences were identified using a validated algorithm based on data from Danish health registries. Follow-up was until death or September 7, 2018. The authors used propensity score matching to adjust for potential preoperative confounders. In the study population of 11,618 individuals, 3,496 (30.1%) had an epidural catheter inserted before surgery. The epidural analgesia group had higher proportions of total IV anesthesia, laparotomies, and rectal tumors, and epidural analgesia was most frequently used between 2009 and 2012. The propensity score-matched study cohort consisted of 2,980 individuals in each group with balanced baseline covariates. Median follow-up was 58 months (interquartile range, 29 to 86). Recurrence occurred in 567 (19.0%) individuals in the epidural analgesia group and 610 (20.5%) in the group without epidural analgesia. The authors found no association between epidural analgesia and recurrence (hazard ratio, 0.91; 95% CI, 0.82 to 1.02) or mortality (hazard ratio, 1.01; 95% CI, 0.92 to 1.10). In colorectal cancer surgery, epidural analgesia was not statistically significantly associated with less cancer recurrence.

The Impact of Patient Characteristics and Tumor Biology on the Accuracy of Preoperative Staging of Colon Cancer in Denmark. A Nationwide Cohort Study.

Simple SummaryThe roles of mismatch repair and other colon tumor characteristics were investigated in a nationwide registry study with data extracted from the Danish Colorectal Cancer Group. Mismatch repair can arise during DNA replication. In this study, 6102 patients were included with a median age of 72 (range 23–97 years). The mismatch repair was deficient in 24% and proficient in 76%. Mismatch repair deficiency impacted the accuracy of the preoperative staging of colon cancer. In the future, mismatch repair status should be taken into consideration in the clinical staging of colon cancer.Background: Colon cancer is a common disease in western populations. The aim of this study was to assess the impact of mismatch repair (MMR) deficiency and other patient and tumor characteristics on the accuracy of preoperative staging by comparing histopathological T- and N-categories of the resected specimen with the preoperative clinical stage in a nationwide cohort of patients treated for colon cancer by elective bowel resection with curative intent. Methods: A register study of a cohort extracted from the Danish Colorectal Cancer Group (DCCG) database, which holds prospective data on all new cases of colon and rectum cancer in Denmark. Patients diagnosed with colon cancer and treated with an elective bowel resection with curative intent in the years 2016–2019 were analyzed. Results: A total of 6102 patients were included (n = 3161 (52%) men and n = 2941 (48%) women) with a median age of 72 years (range 23–97 years). MMR was deficient in 24% of the patients and proficient in 76%. MMR deficiency, tumor sidedness and histopathological type were significant predictors of the accuracy of preoperative staging of colon cancer in univariate and multivariate analysis. MMR status in particular showed a strong impact on the risk of overstaging. Conclusions: MMR deficiency, but also tumor sidedness and to some degree histopathological type, impacted the accuracy of preoperative staging of colon cancer. MMR status should be taken into consideration in everyday clinical staging.

Younger age at onset of colorectal cancer is associated with increased patient’s delay

AimThis study aimed to investigate if younger age at diagnosis of colorectal cancer was associated with a diagnostic delay. The secondary objective was to evaluate if symptomatology varied with age. MethodThe study population consisted of the cohorts from two prospective multicentre studies conducted in Sweden and Denmark, the QoLiRECT and QoLiCOL studies. These studies investigated the quality of life in patients with colorectal cancer. Participants responded to the validated questionnaires used to extract information on patient’s and doctor’s delay as well as first presenting symptoms. Clinical variables were retrieved from the Swedish Colorectal Cancer Registry and the Danish Colorectal Cancer Group Database. Results2574 patients were included, 1085 from QoLiRECT and 1489 from QoLiCOL. The probability of an increased patient’s delay was higher when age decreased by 10 years (the SD in both QoLiRECT and QoLiCOL), adjusted OR 1.19 (95%CI: 1.10; 1.30), p < 0.001. A similar effect was found for doctor’s delay, but the age effect was smaller in this case, adjusted OR 1.05 (95%CI: 0.97; 1.15), p = 0.177. When the age effect was analysed non-linearly, an increased probability of a delay was seen for patients from around 60 years and below. Younger patients were equally or more likely to report the symptoms of blood in stool, diarrhoea, constipation, mucus in faeces, faecal urgency, faecal emptying difficulties and pain compared to older patients. ConclusionYounger patients were more likely to have an increased patient’s delay, probably contributing to a delayed diagnosis of colorectal cancer. Symptomatology at diagnosis was similar irrespective of age.

Robotic versus laparoscopic right colectomy for colon cancer: a nationwide cohort study.

On a national level, the minimally invasive approach is widely adopted in Denmark. The adoption of robotic colorectal surgery is increasing; however, the advantage of a robotic approach in right colectomy is still uncertain. The purpose of this study was to compare robotic right colectomy with laparoscopic right colectomy on a national level. This was a nationwide database study based on data from the Danish Colorectal Cancer Group database. Patients from all colorectal centers in Denmark in the period 2014-2018 treated with curative intend in an elective setting with either robotic or laparoscopic right colectomy were identified. Propensity score matching was performed to adjust for confounding, and the groups were compared on demographics, disease characteristics, operative data, and postoperative and pathology outcomes. Reporting was done in accordance with the STROBE statement. In total, 4002 patients were available for analysis. Propensity score matching in ratio 2:1 identified 718 laparoscopic and 359 robotic cases. After matching, we found a higher lymph node yield in the robotic group compared to the laparoscopic group, (32.5 vs. 28.4, P < 0.001), while radicality, plane of dissection, and pathological disease stages showed no differences. There were no statistical differences in morbidity and mortality. Intracorporeal anastomosis (23.7% vs. 4.5%, P < 0.001) was more commonly performed with a robotic approach. Robotic approach was associated with a significant higher lymph node yield and with similar postoperative morbidity compared to a laparoscopic approach for right colectomy.

Prediction of 90-day mortality after surgery for colorectal cancer using standardized nationwide quality-assurance data.

BackgroundPersonalized risk assessment provides opportunities for tailoring treatment, optimizing healthcare resources and improving outcome. The aim of this study was to develop a 90-day mortality-risk prediction model for identification of high- and low-risk patients undergoing surgery for colorectal cancer.MethodsThis was a nationwide cohort study using records from the Danish Colorectal Cancer Group database that included all patients undergoing surgery for colorectal cancer between 1 January 2004 and 31 December 2015. A least absolute shrinkage and selection operator logistic regression prediction model was developed using 121 pre- and intraoperative variables and internally validated in a hold-out test data set. The accuracy of the model was assessed in terms of discrimination and calibration.ResultsIn total, 49 607 patients were registered in the database. After exclusion of 16 680 individuals, 32 927 patients were included in the analysis. Overall, 1754 (5.3 per cent) deaths were recorded. Targeting high-risk individuals, the model identified 5.5 per cent of all patients facing a risk of 90-day mortality exceeding 35 per cent, corresponding to a 6.7 times greater risk than the average population. Targeting low-risk individuals, the model identified 20.9 per cent of patients facing a risk less than 0.3 per cent, corresponding to a 17.7 times lower risk compared with the average population. The model exhibited discriminatory power with an area under the receiver operating characteristics curve of 85.3 per cent (95 per cent c.i. 83.6 to 87.0) and excellent calibration with a Brier score of 0.04 and 32 per cent average precision.ConclusionPre- and intraoperative data, as captured in national health registries, can be used to predict 90-day mortality accurately after colorectal cancer surgery.