Non-Curative Treatment Choices in Colorectal Cancer: Predictors and Between-Hospital Variations in Denmark: A Population-Based Register Study.

BACKGROUND: Variations in treatment choices have been reported in colorectal cancer (CRC). In the context of national recommendations, we aimed to elucidate predictors and between-hospital variations in refraining from curatively intended surgery and adjuvant chemotherapy in potentially curable colorectal cancer. METHODS: A total of 34,116 patients diagnosed with CRC from 2009 to 2018 were included for analyses on non-curative treatment in this register-based study. Subsequently 8006 patients were included in analyses on adjuvant treatment. Possible predictors included patient-, disease-, socioeconomic- and perioperative-related factors. Logistic regressions were utilized to examine the predictors of a non-curative aim of treatment and no adjuvant chemotherapy. RESULTS: The predictors of non-curative treatment were high age, poor performance, distant metastases and being underweight. Predictors for no adjuvant treatment were high age, poor performance, kidney disease, postoperative complications and living alone. For both outcomes we found between-hospital variations to be present. CONCLUSIONS: Non-curative overall treatment and refraining from adjuvant chemotherapy were associated with well-known risk factors, but the former was also associated with being underweight and the latter was also associated with living alone. Marked between-hospital variations were found and should be examined further.

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

Purpose: 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. Patients and Methods: 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. Results: 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%). Conclusion: 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.

Differences in treatment and survival in young and elderly patients with colorectal cancer.

INTRODUCTION: The incidence of colorectal cancer (CRC) in patients ≤ 40 years of age seems to follow an increasing trend worldwide. Previous studies have reported conflicting data on treatment intensity and survival in young patients with CRC. The aim of this study was to describe treatment and survival data in a national cohort of young Danish CRC patients in the 2001-2013 period and to compare these data with data on a national cohort of elderly patients with CRC. METHODS: In a retrospective study design, we analysed data on pre-operative management, treatment and overall survival in a national cohort of 484 young (18-40 years) and 14,647 elderly (66-75 years) CRC patients. Cox regression models were used to calculate adjusted hazard functions of overall survival. RESULTS: Surgical treatment did not differ markedly between age groups, but young patients received more oncological treatment and had a better stage-specific five-year overall survival than elderly patients. In an adjusted model, the hazard ratio for young patients with stage I-III disease was 0.67 (95% confidence interval (CI): 0.48-0.95) for colon cancer; 0.61 (95% CI: 0.37-0.99) for rectal cancer. CONCLUSION: Despite more advanced clinical stages of disease, young CRC patients had a better survival than elderly CRC patients in this national cohort. FUNDING: The study was funded by Krista og Viggo Petersens Fond; Civilingeniør Bengt Bøgh og Hustru Inge Bøghs Fond; and Arvekapitalen efter Ane Mette Nielsen til lægevidenskabelig forskning ved Vejle Sygehus. TRIAL REGISTRATION: The project was approved by DCCG (2013-03), the Danish Data Protection Agency (2008-58-0035) and the Regional Scientific Ethical Committee for Southern Denmark (S-20130079).

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

PURPOSE: 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. METHODS: This was a retrospective register-based, study design using prospectively collected data from the Danish Colorectal Cancer Group (DCCG) database. All patients aged 18 years 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. RESULTS: 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. CONCLUSION: 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.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

INTRODUCTION: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants. METHODS: We screened 98 patients aged 18-40 with CRC diagnosed in 2010-2013 for variants in MSH2, MSH6, MLH1, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, STK11, PTEN, POLE, POLD1, NTHL1, AXIN2, MSH3, GREM1 and RNF43 using Next Generation Sequencing. Comparisons between patients' characteristics in patients with PGV, and patients without germline variants (NPGV) were analyzed. RESULTS: PGV were detected in twenty-four patients (24.5%), and twenty-one patients (21.1%) had variants in the mismatch repair (MMR) genes associated with LS. Variants in the APC and MUTYH genes were detected in 1% and 4%, respectively. Patients with NPGV had more advanced disease with adverse histopathological features. CONCLUSION: PGV was detected in one in four yCRC patients, and one in five yCRC patients had disease causing variants in the mismatch repair genes associated with LS.

Three different computed tomography obesity indices, two standard methods, and one novel measurement, and their association with outcomes after colorectal cancer surgery.

BACKGROUND: Obesity can be measured by different indices, either as body mass index (BMI) or by more intuitive radiological measurements, and obesity has been shown to have an impact on outcome after colorectal cancer (CRC) surgery. PURPOSE: To investigate whether the thickness of the subcutaneous adipose tissue (SAT) in the abdominal wall can be used as a surrogate for the visceral fat area (VFA)-both measured on computed tomography (CT)-in prediction of short- and long-term outcomes after elective CRC surgery. MATERIAL AND METHODS: Preoperative CT scans of all patients having elective CRC surgery (stages I-III), in two consecutive years at a single-center institution, were used to measure the SAT (mm) and VFA (cm2). BMI was calculated for each patient. The three different obesity indices were used in different analyses in order to predict postoperative complications and overall survival. RESULTS: A BMI >30 kg/m2 was an independent prognostic factor in postoperative complications (odds ratio 3.2, 95% confidence interval [CI] 1.43-7.03). SAT and VFA were not able to predict complications. Patients considered visceral obese according to a high VFA (>130 cm2) had poorer survival (hazard ratio 1.53, 95% CI 1.00-2.36) compared to non-obese patients, but in the adjusted model, VFA lost its predictive power. BMI and SAT were not able to predict mortality. CONCLUSION: The novel measurement of the thickness of SAT in a preoperative setting before elective CRC surgery cannot predict either postoperative complications or overall survival; the other obesity indices had better predictive features.

Clinical characteristics and a rising incidence of early-onset colorectal cancer in a nationwide cohort of 521 patients aged 18-40 years.

BACKGROUND: The incidence of early-onset colorectal cancer (eoCRC) has been reported to increase, and patients with eoCRC seem to be diagnosed at more advanced stages compared to elderly patients. The aim of this study was to describe patient and disease characteristics, symptomatology and the incidence of eoCRC in a national cohort. MATERIALS AND METHODS: 521 eoCRC patients (≤40 years old) diagnosed with histologically verified colorectal cancer (CRC) during the years 2001-2013 were identified in national databases and compared to more than 15,000 CRC patients aged 66-75 years. Age-adjusted incidence was calculated for eoCRC patients and various sub-analyses were performed. RESULTS: More advanced stages were seen in eoCRC patients compared to elderly patients (stage II: p < 0.001, III: p = 0.01 and IV: p < 0.01). Differences were statistically significant in colon cancer, but not in rectal cancer. A significant difference in sex distribution was seen between right and left-sided tumors in the eoCRC group. The age-adjusted incidence rate increased during the study period (1.60-2.55 per 100.000), and significant annual percent changes (APC) were seen in young females (APC = 4.73) and left-sided tumor localization (including rectal cancer) (APC = 4.54), respectively. CONCLUSION: In this nationwide cohort of eoCRC patients, our results confirm that young patients are diagnosed at advanced stages, and that the incidence of eoCRC is increasing.

The day of week of elective colorectal cancer surgery has no impact on mortality and morbidity.

INTRODUCTION: Recent studies have reported an asso-ciation between the day of week of surgery and post-operative mortality, meaning that patients undergoing surgery at the end of the week or during weekends may be at higher risk. The aim of this study was to investigate the influence of the day of week of surgery on mortality and morbidity rates in a national Danish cohort of patients undergoing major elective surgery for colorectal cancer. METHODS: In a register-based study design, all patients undergoing elective major surgery for colorectal cancer in Denmark during a ten-year period (2005-2014) were studied. Patients were identified in the National Colorectal Cancer Database. Any associations between short-time mortality and morbidity rates within 30 days after operation and the day of week of surgery, as well as patient characteristics, treatment data and socioeconomic data were analysed. RESULTS: We were unable to show that the day of week had a significant impact on short-term mortality or on surgical or medical complications. There was no evidence that patients undergoing surgery on Fridays had more risk factors or were more socioeconomically deprived than patients undergoing surgery from Monday to Thursday. CONCLUSIONS: The day of week of operation could not be shown to have any significant impact on the risk of post-operative surgical or medical complications or on short-term mortality in patients undergoing elective surgery for colorectal cancer in Denmark. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Internal herniation underneath the left external iliac artery after radical prostatectomy with extensive lymph node dissection].

A 65-year-old male underwent acute surgery because of a partly ischaemic small intestine due to internal herniation underneath the left external iliac artery. The iatrogenic defect in the peritoneum was created 15 months earlier, when the patient had a robot-assisted radical prostat-ectomy with pelvic lymph node dissection performed. The ischaemic small bowel was resected under a laparotomy, and creation of a temporary stoma was necessary. The peritoneal defect was left open. The patient recovered, and the stoma was surgically closed two months later.

Delay of surgery after stent placement for resectable malignant colorectal obstruction is associated with higher risk of recurrence.

BACKGROUND: Self-expanding metal stents can be used as bridge to elective surgery for acute malignant colonic obstruction. However, the impact on long-term oncological outcome and the optimal timing of surgery are still unknown. METHOD: This was a retrospective multicenter study performed at four colorectal centers. Patients undergoing stent placement as bridge to surgery, between January 2010 and December 2013, were included in the study. Primary outcomes were survival and recurrence rates along with location of the metastases. Additionally, we recorded time from stent placement to elective surgery. Secondary outcomes were postoperative complication rates. Complications were classified according to the Clavien-Dindo classification score. A logistic regression model was used to describe impact of delayed stent removal on risk of recurrence. RESULTS: This study included 112 patients, with a median follow-up of 43 months. Survival rate was 70%. We found a recurrence rate of 37%, primarily local recurrences (17%). Procedure-related complications at the stent placement were seen in 18%, and complications after subsequent elective surgery were seen in 39%. A significantly higher risk of recurrence with increased time from stent placement to elective surgery (OR 5.1 [1.6-15.8], p = 0.005) was found. CONCLUSION: Delay of elective surgery after stent placement may have a negative influence on long-term oncologic outcomes.

Infliximab's influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model.

BACKGROUND: Infliximab, a TNF-α inhibitor, is a potent anti-inflammatory drug in the treatment of inflammatory bowel diseases. Recent studies have investigated the effect of infliximab treatment on postoperative complications such as anastomotic leakage, however, with conflicting results and conclusions. The purpose of this study was to investigate whether a single dose infliximab has an adverse effect on the anastomotic healing process, observed as reduced anastomotic breaking strength and histopathologically verified lower grade of inflammatory response, in the small intestine of a rabbit. METHODS: Thirty New Zealand rabbits (median weight 2.5 kg) were allocated to treatment with an intravenous bolus of either 10 mg/kg infliximab (n = 15) or placebo (n = 15). One week later all rabbits underwent two separate end-to-end anastomoses in the jejunum under general anesthesia. At postoperative day three, the anastomotic breaking strength was determined and histopathological changes were examined. RESULTS: The mean value of anastomotic breaking strength in the placebo group was 1.89 ± 0.36 N and the corresponding value was 1.81 ± 0.33 N in the infliximab treated rabbits. There was no statistically significant difference between the groups (p = 0.51). The infliximab-treated rabbits had a significant lower degree of inflammatory infiltration response compared to the placebo group (p = 0.047). CONCLUSIONS: Our conclusion, limited by the small sample sizes in both groups, is that a single dose of infliximab, given one week prior to surgery, does not have an impact on the anastomotic breaking strength on the third postoperative day in the small intestine of rabbits.