Minimally Invasive Surgery for Colorectal Cancer: Benchmarking Uptake for a Regional Improvement Programme.

BACKGROUND: The uptake of minimally invasive surgery (MIS) for patients with colorectal cancer has progressed at differing rates, both across countries, and within countries. This study aimed to investigate uptake for a regional colorectal cancer improvement programme in England. METHOD: We calculated the proportion of patients receiving elective laparoscopic and robot-assisted surgery amongst those diagnosed with colorectal cancer over 3 time periods (2007-2011, 2012-2016 and 2017-2021) in hospitals participating in the Yorkshire Cancer Research Bowel Cancer Improvement Programme (YCR BCIP). These were benchmarked against national rates. Regression analysis and funnel plots were used to develop a data driven approach for analysing trends in the use of MIS at hospitals in the programme. RESULTS: In England, resections performed by MIS increased from 34.9% to 72.9% for colon cancer and from 28.8% to 72.5% for rectal cancer. Robot-assisted surgery increased from 0.1% to 2.7% for colon cancer and from 0.2% to 7.9% for rectal cancer. Wide variation in the uptake of MIS was observed at a hospital level. Detailed analysis of the YCR BCIP region identified a decreasing number of surgical departments, since the start of the programme, as potential outliers for MIS when compared to the English national average. CONCLUSION: Wide variation in use of MIS for colorectal cancer exists within the English National Health Service and a data-driven approach can help identify outlying hospitals. Addressing some of the challenges behind the uptake of MIS, such as ensuring adequate provision of surgical training and equipment, could help increase its use.

Identifying a common data dictionary across colorectal cancer outcome registries: A mapping exercise to identify opportunities for data dictionary harmonisation.

IMPORTANCE: The development of colorectal cancer outcome registries internationally has been organic, with differing datasets, data definitions and infrastructure across registries which has limited data pooling and international comparison. Currently there is no comprehensive data dictionary identified as a standard. This study is part of an international collaboration that aims to identify areas of data capture and usage which may be optimised to improve understanding of colorectal cancer outcomes. OBJECTIVE: This study aimed to compare and identify commonalities and areas of difference across major colorectal cancer registries. We sought to establish datasets comprising of mutually collected common fields, and a combined comprehensive dataset of all collected fields across major registries to aid in establishing a future colorectal cancer registry database standard. DESIGN AND METHODS: This mixed qualitative and quantitative study compared data dictionaries from three major colorectal cancer outcome registries: Bowel Cancer Outcomes Registry (BCOR) (Australia and New Zealand), National Bowel Cancer Audit (NBOCA) (United Kingdom) and Dutch ColoRectal Audit (DCRA) (Netherlands). Registries were compared and analysed thematically, and a common dataset and combined comprehensive dataset were developed. These generated datasets were compared to data dictionaries from Sweden (SCRCR), Denmark (DCCG), Argentina (BNCCR-A) and the USA (NAACCR and ACS NSQIP). Fields were assessed against prominent quality indicator metrics from the literature and current case-use. RESULTS: We developed a combined comprehensive dataset of 225 fields under seven domains: demographic, pre-operative, operative, post-operative, pathology, neoadjuvant therapy, adjuvant therapy, and follow up/recurrence. A common dataset was developed comprising 38 overlapping fields, showing a low degree of mutually collected data, especially in preoperative, post operative and adjuvant therapy domains. The BNCCR-A, SCRCR and DCCG databases all contained a high percentage of common dataset fields. Fields were poorly comparable when viewed form current quality indicator metrics. CONCLUSION: This study mapped data dictionaries of prominent colorectal cancer registries and highlighted areas of commonality and difference The developed common field dataset provides a foundation for registries to benchmark themselves and work towards harmonisation of data dictionaries. This has the potential to enable meaningful large-scale international outcomes research.

Challenges presented by complete response to immune checkpoint blockade in patients with dMMR colorectal cancer: A case report.

INTRODUCTION: Early clinical trials have demonstrated remarkable responses to immune checkpoint blockade (ICB) in patients with colorectal cancers with deficient mismatch repair (dMMR) mechanisms. The precise role immunotherapy will play in the treatment of these patients is undefined, with these agents likely to produce new challenges as well as opportunities. PRESENTATION OF CASE: A 74-year-old patient was diagnosed with a locally advanced dMMR adenocarcinoma in the transverse colon with clinical suspicion of peritoneal metastases (cT4N2M1). The burden of disease was assessed as incurable, and a referral was made for palliative oncological treatment. After 5 months of treatment with pembrolizumab, a complete radiological response in the primary tumour was seen although there was still radiological suspicion of peritoneal and lymph node metastases. The patient underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but unfortunately died 6 weeks later due to complications. Final histology of the surgical specimen showed no evidence of residual disease (ypT0N0M0). DISCUSSION: This case highlights the opportunities and challenges presented by the efficacy of ICB in dMMR colorectal cancer. These agents were able to cure a patient who had disseminated disease presumed to be incurable at the time of diagnosis. However, due to current limitations in determining the degree of response to ICB, this result could only be confirmed after major surgery, which ultimately led to the patient's death. CONCLUSION: ICB can lead to dramatic responses in patients with dMMR colorectal cancers. Major challenges remain in differentiating complete and partial responders and determining the indications for conventional surgery.

DREAMS: deep read-level error model for sequencing data applied to low-frequency variant calling and circulating tumor DNA detection.

Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions. Using DREAMS, we develop statistical methods for variant calling (DREAMS-vc) and cancer detection (DREAMS-cc). For evaluation, we generate deep targeted NGS data of matching tumor and plasma DNA from 85 colorectal cancer patients. The DREAMS approach performs better than state-of-the-art methods for variant calling and cancer detection.

Anastomotic perfusion assessment with indocyanine green in robot-assisted low-anterior resection, a multicenter study of interobserver variation.

BACKGROUND: Securing sufficient blood perfusion to the anastomotic area after low-anterior resection is a crucial factor in preventing anastomotic leakage (AL). Intra-operative indocyanine green fluorescent imaging (ICG-FI) has been suggested as a tool to assess perfusion. However, knowledge of inter-observer variation among surgeons in the interpretation of ICG-FI is sparse. Our primary objective was to evaluate inter-observer variation among surgeons in the interpretation of bowel blood-perfusion assessed visually by ICG-FI. Our secondary objective was to compare the results both from the visual assessment of ICG and from computer-based quantitative analyses of ICG-FI between patients with and without the development of AL. METHOD: A multicenter study, including patients undergoing robot-assisted low anterior resection with stapled anastomosis. ICG-FI was evaluated visually by the surgeon intra-operatively. Postoperatively, recorded videos were anonymized and exchanged between centers for inter-observer evaluation. Time to visibility (TTV), time to maximum visibility (TMV), and time to wash-out (TWO) were visually assessed. In addition, the ICG-FI video-recordings were analyzed using validated pixel analysis software to quantify blood perfusion. RESULTS: Fifty-five patients were included, and five developed clinical AL. Bland-Altman plots (BA plots) demonstrated wide inter-observer variation for visually assessed fluorescence on all parameters (TTV, TMV, and TWO). Comparing leak-group with no-leak group, we found no significant differences for TTV: Hazard Ratio; HR = 0.82 (CI 0.32; 2.08), TMV: HR = 0.62 (CI 0.24; 1.59), or TWO: HR = 1.11 (CI 0.40; 3.11). In the quantitative pixel analysis, a lower slope of the fluorescence time-curve was found in patients with a subsequent leak: median 0.08 (0.07;0.10) compared with non-leak patients: median 0.13 (0.10;0.17) (p = 0.04). CONCLUSION: The surgeon's visual assessment of the ICG-FI demonstrated wide inter-observer variation, there were no differences between patients with and without AL. However, quantitative pixel analysis showed a significant difference between groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04766060.

Differences in the management of patients requiring an emergency resection for colonic cancer in two European populations.

BACKGROUND: Patients with colonic cancer who require emergency colonic cancer surgery often experience poorer outcomes compared with their elective counterparts. In this setting, several treatments approaches are available. In 2009, Danish guidelines recommended treatment with stent for obstruction in left-sided tumours as a bridge to surgery, if expertise is accessible. The aim of this study was to compare the use of elective and emergency resections for colonic cancer and postoperative mortality in two similar demographic populations. METHODS: All patients who underwent a major resection for colonic cancer, between 2005 and 2016 in Denmark and Yorkshire (UK) were identified. The proportion undergoing emergency surgery, the proportion receiving a stent procedure before their resection, and 30-day postoperative mortality were compared between the populations. Logistic regression was used to determine changes in the proportion of those undergoing emergency surgery and 30-day postoperative mortality. RESULTS: Out of 45 397 patients treated during the study interval, 41 880 were selected. Emergency surgery decreased in Denmark from 16.6 per cent in 2005-07 to 12.9 per cent in 2014-16, but increased in Yorkshire (13.5 per cent to 16.8 per cent). Danish patients with left-sided tumours were less likely to undergo emergency surgery (risk ratio 0.90, 95 per cent c.i. 0.82 to 0.99) and an increase in stent use coincided with a statistically significant decrease in emergency surgery in these patients. Thirty-day postoperative mortality in all resections (elective and emergency) decreased in both populations, but a larger decrease was observed in Denmark (7.7 per cent to 3.0 per cent in Denmark and 7.1 per cent to 3.3 per cent in Yorkshire). CONCLUSION: Patients in Denmark experienced a reduction in the use of emergency resection and increase in stenting procedures, following the policy implemented in some departments of converting potential emergency resections into elective resections.

Trends in rectal cancer incidence, relative survival, and mortality in Denmark during 1978-2018.

OBJECTIVE: Rectal cancer is common in developed countries, though incidence varies globally. We assessed time trends in incidence, relative survival and mortality in Denmark. METHODS: Rectal cancer cases ( N = 50 461) diagnosed in 1978-2018 were identified in the Danish Cancer Registry. We calculated age-standardized incidence rates, overall and according to sex and age. Average annual percentage changes (AAPC) were estimated using Poisson regression. We estimated 5-year relative survival and evaluated the effect of age, calendar year of diagnosis, sex and stage of disease on mortality using the Cox proportional hazards model. RESULTS: The incidence of rectal cancer tended to decrease in all age groups and both sexes during 1978-1997, but increased since 1998, more in men (AAPC = 2.05%; 95% CI,1.80; 2.31) than in women (AAPC = 0.99%; 95% CI,0.68; 1.30). It increased in men until 79 years and in women up to 59 years. Mortality decreased over time when adjusting for age, stage and sex. Overall, men had the highest 5-year mortality after adjusting for age, calendar period and stage. Five-year relative survival improved (1978-2018) for all stages. Initially, the overall 5-year relative survival tended to be better for women, but in recent years, it has been similar in both sexes. CONCLUSION: Incidence of rectal cancer increased in the last two decades, most markedly in women 59 years and younger. Mortality decreased when adjusting for age and stage. Relative survival improved over time more for men than for women, so in recent years, it has been virtually identical in men and women.

Influence of age on surgical treatment and postoperative outcomes of patients with colorectal cancer in Denmark and Yorkshire, England.

AIM: Denmark and Yorkshire are demographically similar and both have undergone changes in their management of colorectal cancer to improve outcomes. The differential provision of surgical treatment, especially in the older age groups, may contribute to the magnitude of improved survival rates. This study aimed to identify differences in the management of colorectal cancer surgery and postoperative outcomes according to patient age between Denmark and Yorkshire. METHOD: This was a retrospective population-based study of colorectal cancer patients diagnosed in Denmark and Yorkshire between 2005 and 2016. Proportions of patients undergoing major surgical resection, postoperative mortality and relative survival were compared between Denmark and Yorkshire across several age groups (18-59, 60-69, 70-79 and ≥80 years) and over time. RESULTS: The use of major surgical resection was higher in Denmark than in Yorkshire, especially for patients aged ≥80 years (70.5% versus 50.5% for colon cancer, 49.3% versus 38.1% for rectal cancer). Thirty-day postoperative mortality for Danish patients aged ≥80 years was significantly higher than that for Yorkshire patients with colonic cancer [OR (95% CI) = 1.22 (1.07, 1.38)] but not for rectal cancer or for 1-year postoperative mortality. Relative survival significantly increased in all patients aged ≥80 years except for Yorkshire patients with colonic cancer. CONCLUSION: This study suggests that there are major differences between the management of elderly patients with colorectal cancer between the two populations. Improved selection for surgery and better peri- and postoperative care in these patients appears to improve long-term outcomes, but may come at the cost of a higher 30-day mortality.

Renin-angiotensin system blockers and 1-year mortality in patients with post-operative acute kidney injury.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACE-I) and angiotensin-receptor blocker (ARB) users may be associated with increased mortality in patients with post-operative acute kidney injury (AKI), but data are limited. We studied whether users of ACE-I/ARBs with AKI after colorectal cancer surgery (CRC) were associated with increased 1-year mortality after AKI. METHODS: This population-based cohort study in Northern Denmark included patients with AKI within 7 days after CRC surgery during 2005-2014. From reimbursed prescriptions, patients were classified as ACE-I/ARB current, former, or non-users. We computed the cumulative 30-day and 1-year mortality after AKI with 95% confidence intervals (95% CI) using the Kaplan-Meier method (1-survival function). Hazard ratios (HRs) comparing mortality in current and former users with non-users were computed by Cox proportional hazards regression analyses, controlling for potential confounders. RESULTS: We identified 10 713 CRC surgery patients. A total of 2000 patients had AKI and were included. Thirty-day mortality was 16.5% (95% CI 13.7-19.8), 16.2% (95% CI 11.3-22.8), and 13.4% (95% CI 11.6-15.4) for current, former, and non-users. Adjusted HR was 1.26 (95% CI 0.96-1.65) and 1.19 (95% CI 0.78-1.82) for current and former users compared with non-users. One-year mortality rates were 26.4% (95% CI 22.9-30.4), 29.8% (95% CI 23.2-37.8), and 24.7% (95% CI 22.4-27.2) in current, former, and non-users. Compared with non-users, the adjusted 1-year HR for death in current and former users were 1.29 (95% CI 0.96-1.73) and 1.11 (95% CI 0.91-1.35). CONCLUSION: Based on our findings, current users of ACE-I/ARB may possibly have a small increase in mortality rate in the year after post-operative AKI, although the degree of certainty is low.

The Validity of Registered Synchronous Peritoneal Metastases from Colorectal Cancer in the Danish Medical Registries.

INTRODUCTION: Treatment options for peritoneal metastases (PM) from colorectal cancer (CRC) have increased, their efficiency should be monitored. For this purpose, register-based data on PM can be used, if valid. PURPOSE: We aimed to evaluate the completeness and positive predictive value (PPV) of synchronous peritoneal metastases (S-PM) registered among CRC patients in the Danish National Patient Register (DNPR) and/or the Danish National Pathology Register (the DNPatR) using the Danish Colorectal Cancer Group database (DCCG) as a reference. PATIENTS AND METHODS: We identified Danish patients with newly diagnosed primary CRC in the DCCG during 2014-2015. S-PM were routinely registered in the DCCG. We excluded patients with non-CRC cancers and identified S-PM using all three registries. We estimated the completeness and the PPV of registered S-PM in the DNPR, the DNPatR and the DNPR and/or the DNPatR (DNPR/DNPatR) in combination using the DCCG as the reference. We stratified by age, gender, WHO performance status, tumour location and distant metastases to liver and/or lungs. RESULTS: We identified 9142 patients with CRC in DCCG. In DCCG, 366 patients were registered with S-PM, among whom 213 in DCCG only, whereas 153 in DCCG and in at least one of DNPR and/or DNPatR. In DNPR/DNPatR, S-PM was registered with a completeness of 42% [95% CI: 37-47] and a PPV of 60% [95% CI: 54-66]. In the DNPR only, the completeness was 32% [95% CI: 27-37] and the PPV 57% [95% CI: 50-64]. The completeness in the DNPatR was 19% [95% CI: 15-23] and the PPV was 76% [95% CI: 68-85]. In the DNPR/DNPatR patients aged <60 years (57% [95% CI: 46-69]), patients with WHO performance status 0 (46% [95% CI: 37-54]) and patients with no distant metastases (58% [95% CI: 50-65]) were registered with a higher completeness. CONCLUSION: Our algorithm demonstrates that the DNPR/DNPatR captures less than half of CRC patients with S-PM. Potential candidates for curative treatment options are registered with a higher completeness. Clinicians should be encouraged to register the presence of S-PM to increase the validity of register-based S-PM data.

The Influence of Perioperative Fluid Therapy on N-terminal-pro-brain Natriuretic Peptide and the Association With Heart and Lung Complications in Patients Undergoing Colorectal Surgery: Secondary Results of a Clinical Randomized Assessor-blinded Multicenter Trial.

OBJECTIVE: To investigate the influence of intravenous (iv) fluid volumes on the secretion of N-terminal-pro-brain natriuretic peptide (NT-Pro-BNP) in colorectal surgical patients and its association with cardiopulmonary complications (CPC). In addition, to examine if preoperative NT-Pro-BNP can predict the risk for postoperative CPC. METHODS: Blood samples from patients enrolled in a previously published clinical randomized assessor-blinded multicenter trial were analyzed. Included were adult patients undergoing elective colorectal surgery with the American-Society-of-Anesthesiologists-scores of 1-3. Samples from 135 patients were available for analysis. Patients were allocated to either a restrictive (R-group) or a standard (S-group) iv-fluid regimen, commencing preoperatively and continuing until discharge. Blood was sampled every morning until the fourth postoperative day. The primary outcome for this study was NT-Pro-BNP changes and its association with fluid therapy and CPC. RESULTS: The S-group received more iv-fluid than the R-group on the day-of-surgery [milliliter, median (range) 6485 (4401-10750) vs 3730 (2250-8510); P < 0.001] and on the first postoperative day. NT-Pro-BNP was elevated in the S-group compared with the R-group on all postoperative days [area under the curve: median (interquartile range) pg/mL: 3285 (1697-6179) vs 1290 (758-3719); P < 0.001 and in patients developing CPC vs no-CPC (area under the curve), median (interquartile range): 5196 (1823-9061) vs 1934 (831-5301); P = 0.005]. NT-pro-BNP increased with increasing fluid volumes all days (P < 0.003). Preoperative NT-Pro-BNP predicted CPC [odds ratio (confidence interval): 1.573 (0.973-2.541), P = 0.032; positive predictive value = 0.257, negative predictive value = 0.929]. CONCLUSIONS: NT-pro-BNP increases with iv-fluid volumes given to colorectal surgical patients, and the level of NT-Pro-BNP is associated with CPC. Preoperative NT-Pro-BNP is predictive for CPC, but the diagnostic value is low.Clinicaltrials.gov NCT03537989.

Pelvic insufficiency fractures, dose volume parameters and plan optimization after radiotherapy for rectal cancer.

Pelvic insufficiency fractures (PIF) is a known but under-acknowledged late effect of pelvic radiotherapy. In rectal cancer, studies describing incidence of PIF and relation to dose volume relationships are lacking. The aim of this study was (i) to analyse dose volume histograms (DVH) from pelvic bones in patients with and without PIF, and (ii) to determine bone sparing capacity of 2 and 3 arc volumetric arc therapy (VMAT), intensity modulated radiotherapy (IMRT) and proton beam therapy (PBT), in rectal cancer patients treated with chemoradiotherapy (CRT). MATERIAL AND METHODS: Patients treated with CRT for primary rectal cancer underwent a 3-year pelvic MRI for identification of PIFs. Bone structures were retrospectively delineated, and DVHs were re-calculated. Comparative planning was done with 2 (original) and 3 arc VMAT, fixed field IMRT and PBT plans. RESULTS: 27 patients (18 men, mean age 64 years) were included and PIFs were identified in 9 (33%), most (n = 6) had multiple fracture sites. In general, patients with PIFs received higher doses to pelvic bones, and V30 Gy to the sacroiliac joint was non-significantly higher in patients with PIF 68.5% (60.1-69.3 IQR) vs. 56% (54.1-66.6 IQR), p = 0.064. Comparative planning showed that especially 3 arc VMAT and proton beam therapy could be optimized for bone. CONCLUSIONS: Patients, treated with VMAT based CRT for rectal cancer, have high rates of PIFs after 3 years. Patients with PIFs tended to have received higher doses to sacroiliac joints. Comparative planning demonstrated most pronounced bone sparing capacity of 3 arc VMAT and with PBT having the potential to further lower doses. These results should be validated in larger and preferably prospective cohorts.

Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer.

IMPORTANCE: Novel sensitive methods for detection and monitoring of residual disease can improve postoperative risk stratification with implications for patient selection for adjuvant chemotherapy (ACT), ACT duration, intensity of radiologic surveillance, and, ultimately, outcome for patients with colorectal cancer (CRC). OBJECTIVE: To investigate the association of circulating tumor DNA (ctDNA) with recurrence using longitudinal data from ultradeep sequencing of plasma cell-free DNA in patients with CRC before and after surgery, during and after ACT, and during surveillance. DESIGN, SETTING, AND PARTICIPANTS: In this prospective, multicenter cohort study, ctDNA was quantified in the preoperative and postoperative settings of stages I to III CRC by personalized multiplex, polymerase chain reaction-based, next-generation sequencing. The study enrolled 130 patients at the surgical departments of Aarhus University Hospital, Randers Hospital, and Herning Hospital in Denmark from May 1, 2014, to January 31, 2017. Plasma samples (n = 829) were collected before surgery, postoperatively at day 30, and every third month for up to 3 years. MAIN OUTCOMES AND MEASURES: Outcomes were ctDNA measurement, clinical recurrence, and recurrence-free survival. RESULTS: A total of 130 patients with stages I to III CRC (mean [SD] age, 67.9 [10.1] years; 74 [56.9%] male) were enrolled in the study; 5 patients discontinued participation, leaving 125 patients for analysis. Preoperatively, ctDNA was detectable in 108 of 122 patients (88.5%). After definitive treatment, longitudinal ctDNA analysis identified 14 of 16 relapses (87.5%). At postoperative day 30, ctDNA-positive patients were 7 times more likely to relapse than ctDNA-negative patients (hazard ratio [HR], 7.2; 95% CI, 2.7-19.0; P < .001). Similarly, shortly after ACT ctDNA-positive patients were 17 times (HR, 17.5; 95% CI, 5.4-56.5; P < .001) more likely to relapse. All 7 patients who were ctDNA positive after ACT experienced relapse. Monitoring during and after ACT indicated that 3 of the 10 ctDNA-positive patients (30.0%) were cleared by ACT. During surveillance after definitive therapy, ctDNA-positive patients were more than 40 times more likely to experience disease recurrence than ctDNA-negative patients (HR, 43.5; 95% CI, 9.8-193.5 P < .001). In all multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathologic risk factors. Serial ctDNA analyses revealed disease recurrence up to 16.5 months ahead of standard-of-care radiologic imaging (mean, 8.7 months; range, 0.8-16.5 months). Actionable mutations were identified in 81.8% of the ctDNA-positive relapse samples. CONCLUSIONS AND RELEVANCE: Circulating tumor DNA analysis can potentially change the postoperative management of CRC by enabling risk stratification, ACT monitoring, and early relapse detection.

Treatment and survival of rectal cancer patients over the age of 80 years: a EURECCA international comparison.

BACKGROUND: The optimal treatment strategy for older rectal cancer patients remains unclear. The current study aimed to compare treatment and survival of rectal cancer patients aged 80+. METHODS: Patients of ≥80 years diagnosed with rectal cancer between 2001 and 2010 were included. Population-based cohorts from Belgium (BE), Denmark (DK), the Netherlands (NL), Norway (NO) and Sweden (SE) were compared side by side for neighbouring countries on treatment strategy and 5-year relative survival (RS), adjusted for sex and age. Analyses were performed separately for stage I-III patients and stage IV patients. RESULTS: Overall, 19 634 rectal cancer patients were included. For stage I-III patients, 5-year RS varied from 61.7% in BE to 72.3% in SE. Proportion of preoperative radiotherapy ranged between 7.9% in NO and 28.9% in SE. For stage IV patients, 5-year RS differed from 2.8% in NL to 5.6% in BE. Rate of patients undergoing surgery varied from 22.2% in DK to 40.8% in NO. CONCLUSIONS: Substantial variation was observed in the 5-year relative survival between European countries for rectal cancer patients aged 80+, next to a wide variation in treatment, especially in the use of preoperative radiotherapy in stage I-III patients and in the rate of patients undergoing surgery in stage IV patients.

Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison.

BACKGROUND: Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients. SUBJECTS, MATERIALS, AND METHODS: National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001-2006 and 2007-2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame. RESULTS: Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II-IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54-0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69-0.96) compared with Belgium. CONCLUSION: There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed. IMPLICATIONS FOR PRACTICE: With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.

Open versus laparoscopic rectal cancer resection and risk of subsequent incisional hernia repair and paracolostomy hernia repair: a nationwide population-based cohort study.

OBJECTIVE: To investigate the risk of incisional hernia repair (IHR) and paracolostomy hernia repair (PHR) following open and laparoscopic rectal cancer resection with curative intent. BACKGROUND: Laparoscopic rectal cancer resection has been implemented to varying degrees around the world. IHR and PHR following open and laparoscopic rectal cancer resection have only been sparingly evaluated. METHODS: Patients who underwent rectal cancer resection were identified in the Danish Colorectal Cancer Group's database. To identify IHR and PHR following rectal cancer resection, we linked data to the Danish Ventral Hernia Database. The absolute risk of IHR and PHR was estimated as cumulative incidence proportions, treating death as competing risk. We used Cox proportional hazard regression analysis with multivariable adjustment to compute hazard ratios (HRs) comparing open and laparoscopic approach. RESULTS: The 5-year risk of IHR was 4.1% among patients undergoing open resection (n = 3090) and 3.2% among those undergoing laparoscopic resection (n = 3099), corresponding to a risk difference of 0.9% (95% CI 0.0-2.0, P = 0.057). Laparoscopic rectal resection was not associated with lower risk of IHR (adjusted HR 0.94, 95% CI 0.67-1.31, P = 0.709). A total of 2577 patients had a colostomy at rectal cancer resection and the 5-year risk of PHR was 2.1% after open surgery compared with 6.7% after laparoscopic surgery, corresponding to a risk difference of -4.6% (95% CI -6.4 to -2.7, P < 0.001). Laparoscopic surgery was associated with increased risk of PHR (adjusted HR 2.56, 95% CI 1.53-4.29, P < 0.001). CONCLUSION: We observed no association between surgical approach of rectal cancer resection and subsequent IHR. Laparoscopic surgery was associated with increased risk of PHR.

The prognostic impact of bowel perforation following self-expanding metal stent as a bridge to surgery in colorectal cancer obstruction.

BACKGROUND: Self-expanding metallic stent (SEMS) as a bridge to surgery for obstructive colorectal cancer may cause perforation of the tumor and thereby induce tumor spread and increase risk of recurrence, and eventually death. Evidence of the prognostic impact of SEMS-related perforation is, however, sparse. We conducted a long-term follow-up study to compare characteristics, overall survival, and recurrence rates between patients with and without SEMS-related bowel perforation. METHOD: This long-term follow-up study included obstructive colorectal cancer patients treated with SEMS as a bridge to surgery during a 10-year period at two primary and tertiary referral centers. The primary outcome was overall survival, and the secondary outcome was recurrence. We compared mortality and recurrence in patients with and without SEMS-related perforations by Cox proportion hazard regression, adjusting for age, comorbidity, and disease stage. The recurrence risk was examined for patients undergoing curative resection and computed treating death as a competing risk. RESULTS: From January 2004 to December 2013, 123 patients were treated with SEMS as a bridge to surgery. Of these patients, 15 (12%) had SEMS-related perforations. Median follow-up was 4.8 years (range 0.0-10.9 years). The overall 5-year survival was 58% for the entire cohort, but 37 and 61% for patients with and without perforations, respectively, corresponding to an adjusted hazard ratio of 1.6 (95% CI 0.8-3.3) in favor of patient without perforation. The overall 5-year recurrence rate was 34%, but 45 and 33% for patients with and without perforation, respectively, corresponding to an adjusted hazard ratio of 1.4 (95% CI 0.5-3.7) in disfavor of patients with perforation. CONCLUSION: SEMS-related perforations are common and may be associated with decreased survival and increased recurrence, although estimates in this study were imprecise.

Registries on peritoneal surface malignancies throughout the world, their use and their options.

AIM: The treatment of peritoneal surface malignancies ranges from palliative care to full cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy, HIPEC. Ongoing monitoring of patient recruitment and volume is usually carried out through dedicated registries. With multiple registries available worldwide, we sought to investigate the nature, extent and value of existing worldwide CRS and HIPEC registries. METHODS: A questionnaire was sent out to all known major treatment centres. The questionnaire covers: general purpose of the registry; inclusion criteria in the registry; the date the registry was first established; volume of patients in the registry and description of the data fields in the registries. Finally, the population size of the catchment area of the registry was collected. RESULTS: Twenty-seven questionnaires where returned. National databases are established in northwest European countries. There are five international general databases. Most database collect data on patients who have undergone an attempt to CRS and HIPEC. Two registries collect data on all patients with peritoneal carcinomatosis regardless the treatment. Most registries are primarily used for tracking outcomes and complications. When correlating the number of cases of CRS and HIPEC that are performed to the catchment area of the various registry, a large variation in the number of performed procedures related to the overall population was noted, ranging from 1.3 to 57 patients/million year with an average of 15 patients/1 million year. CONCLUSIONS: CRS and HIPEC is a well-established treatment for peritoneal surface malignancies worldwide. However, the coverage as well as the registration of treatment procedures differs widely. The most striking difference is the proportion of HIPEC procedures per capita which ranges from 1.3 to 57 patients per million. This suggests either a difference in patient selection, lack of access to HIPEC centres or lack of appropriate data collection.

Danish Colorectal Cancer Group Database.

AIM OF DATABASE: The aim of the database, which has existed for registration of all patients with colorectal cancer in Denmark since 2001, is to improve the prognosis for this patient group. STUDY POPULATION: All Danish patients with newly diagnosed colorectal cancer who are either diagnosed or treated in a surgical department of a public Danish hospital. MAIN VARIABLES: The database comprises an array of surgical, radiological, oncological, and pathological variables. The surgeons record data such as diagnostics performed, including type and results of radiological examinations, lifestyle factors, comorbidity and performance, treatment including the surgical procedure, urgency of surgery, and intra- and postoperative complications within 30 days after surgery. The pathologists record data such as tumor type, number of lymph nodes and metastatic lymph nodes, surgical margin status, and other pathological risk factors. DESCRIPTIVE DATA: The database has had >95% completeness in including patients with colorectal adenocarcinoma with >54,000 patients registered so far with approximately one-third rectal cancers and two-third colon cancers and an overrepresentation of men among rectal cancer patients. The stage distribution has been more or less constant until 2014 with a tendency toward a lower rate of stage IV and higher rate of stage I after introduction of the national screening program in 2014. The 30-day mortality rate after elective surgery has been reduced from >7% in 2001-2003 to <2% since 2013. CONCLUSION: The database is a national population-based clinical database with high patient and data completeness for the perioperative period. The resolution of data is high for description of the patient at the time of diagnosis, including comorbidities, and for characterizing diagnosis, surgical interventions, and short-term outcomes. The database does not have high-resolution oncological data and does not register recurrences after primary surgery. The Danish Colorectal Cancer Group provides high-quality data and has been documenting an increase in short- and long-term survivals since it started in 2001 for both patients with colon and rectal cancers.

Improved survival of colorectal cancer in Denmark during 2001-2012 - The efforts of several national initiatives.

Background The Danish Colorectal Cancer Group (DCCG) established a national clinical database in 2001 with the aim to monitor and improve outcome of colorectal cancer patients. Since 2000 several national initiatives have been taken to improve cancer outcome. In the present study we used DCCG data to evaluate mortality and survival of CRC patients with focus on comorbidity, stage, and perioperative treatment. Material and methods Patients notified to the DCCG database from 2001 to 2012 were included. Patients with primary cancer of the colon and rectum were analyzed separately. Analyses were stratified according to gender, comorbidity, Union for International Cancer Control (UICC) stage, and operative priority (elective/emergency/no surgery). Data were stratified into three time periods (2001-2004, 2005-2008, 2009-2012). Mortality and survival were age adjusted. Results In total 29 385 patients with colon cancer and 15 213 patients with rectal cancer were included. The stage distribution was almost stable over time. The mortality rate per 100 patient year within one year decreased from 32 to 26 in colon cancer and from 26 to 19 in rectal cancer with associated improvements in absolute survival from 73% to 78% in colon cancer and from 78% to 83% in rectal cancer. The five-year relative survival of colon cancer improved from 58% to 63% and in rectal cancer from 59% to 65%. Comorbidity had major negative impact on outcome. Irrespective of tumor location, outcome improved relatively more in patients with stage III and IV disease. The proportion of patients who were spared surgery increased from 8% to 15% in colon cancer and from 13% to 19% in rectal cancer, and these changes were associated with improved outcome for rectal cancer patients, whereas outcome worsened for colon cancer patients. Conclusion The Danish efforts to improve outcome of cancer have succeeded with improved outcomes in patients with colorectal cancer.