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.

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.

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.

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.

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.

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.

Iatrogenic ureteral injury in colorectal cancer surgery: a nationwide study comparing laparoscopic and open approaches.

BACKGROUND: Iatrogenic ureteral injury is a rare complication in colorectal surgery. We aimed to investigate the risk of ureteral injury among patients with colorectal cancer operated on with curative intent in Denmark with laparoscopic and open technique. METHOD: The study was based on the Danish National Colorectal Cancer database (DCCG) and included patients treated with intended curative resection for colorectal cancer between 2005 and 2011. From the DCCG database, we extracted data on intraoperative urinary tract injuries. To identify urinary tract injuries not recognized at the time of surgery but within 30 days after surgery, we cross-linked data with the National Patient Registry. All ureteral injuries were confirmed by medical record review. Data were analyzed separately for colon and rectal cancer. RESULTS: A total of 18,474 patients had a resection for colorectal cancer. Eighty-two ureteral injuries were related to colorectal surgery. The rate of ureteral injuries in the entire cohort was 0.44 %, with 37 (0.59 %) injuries in the laparoscopic group (n = 6,291) and 45 (0.37 %) injuries in the open group (n = 12,183), (P = 0.03). No difference in ureteral injury was found in relation to surgical approach in colon cancer patients. In rectum cancer patients (n = 5,959), the laparoscopic approach was used in 1,899 patients, and 19 (1.00 %) had ureteral injuries, whereas 17 (0.42 %) of 4,060 patients who underwent an open resection had a ureteral injury. In multivariate analysis adjusted for age, gender, ASA score, BMI, tumor stage, preoperative chemo-radiation, calendar year, and specialty of the surgeon, the laparoscopic approach was associated with an increased risk of ureteral injury, OR = 2.67; 95 % CI 1.26-5.65. CONCLUSION: In this nationwide study laparoscopic surgery for rectal cancer with curative intent was associated with a significantly increased risk of iatrogenic ureteral injury compared to open surgery.

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.

Workload and surgeon's specialty for outcome after colorectal cancer surgery.

BACKGROUND: A large body of research has focused on investigating the effects of healthcare provider volume and specialization on patient outcomes including outcomes of colorectal cancer surgery. However there is conflicting evidence about the role of such healthcare provider characteristics in the management of colorectal cancer. OBJECTIVES: To examine the available literature for the effects of hospital volume, surgeon caseload and specialization on the outcomes of colorectal, colon and rectal cancer surgery. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL), and LILACS using free text search words (as well as MESH-terms). We also searched Medline (January 1990-September 2011), Embase (January 1990-September 2011) and registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Non-randomised and observational studies that compared outcomes for colorectal cancer, colon cancer and rectal cancer surgery (overall 5-year survival, five year disease specific survival, operative mortality, 5-year local recurrence rate, anastomotic leak rate, permanent stoma rate and abdominoperineal excision of the rectum rate) between high volume/specialist hospitals and surgeons and low volume/specialist hospitals and surgeons. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias in included studies. Results were pooled using the random effects model in unadjusted and case-mix adjusted meta-analyses. MAIN RESULTS: Overall five year survival was significantly improved for patients with colorectal cancer treated in high-volume hospitals (HR=0.90, 95% CI 0.85 to 0.96), by high-volume surgeons (HR=0.88, 95% CI 0.83 to 0.93) and colorectal specialists (HR=0.81, 95% CI 0.71 to 0.94). Operative mortality was significantly better for high-volume surgeons (OR=0.77, 95% CI 0.66 to 0.91) and specialists (OR=0.74, 95% CI 0.60 to 0.91), but there was no significant association with higher hospital caseload (OR=0.93, 95% CI 0.84 to 1.04) when only case-mix adjusted studies were included. There were differences in the effects of caseload depending on the level of case-mix adjustment and also whether the studies originated in the US or in other countries. For rectal cancer, there was a significant association between high-volume hospitals and improved 5-year survival (HR=0.85, 95% CI 0.77 to 0.93), but not with operative mortality (OR=0.97, 95% CI 0.70 to 1.33); surgeon caseload had no significant association with either 5-year survival (HR=0.99, 95% CI 0.86 to 1.14) or operative mortality (OR=0.86, 95% CI 0.62 to 1.19) when case-mix adjusted studies were reviewed. Higher hospital volume was associated with significantly lower rates of permanent stomas (OR=0.64, 95% CI 0.45 to 0.90) and APER (OR=0.55, 95% CI 0.42 to 0.72). High-volume surgeons and specialists also achieved lower rates of permanent stoma formation (0.75, 95% CI 0.64 to 0.88) and (0.70, 95% CI 0.53 to 0.94, respectively). AUTHORS' CONCLUSIONS: The results confirm clearly the presence of a volume-outcome relationship in colorectal cancer surgery, based on hospital and surgeon caseload, and specialisation. The volume-outcome relationship appears somewhat stronger for the individual surgeon than for the hospital; particularly for overall 5-year survival and operative mortality, there were differences between US and non-US data, suggesting provider variability at hospital level between different countries, making it imperative that every country or healthcare system must establish audit systems to guide changes in the service provision based on local data, and facilitate centralisation of services as required. Overall quality of the evidence was low as all included studies were observational by design. In addition there were discrepancies in the definitions of caseload and colorectal specialist. However ethical challenges associated with the conception of randomised controlled trials addressing the volume outcome relationship makes this the best available evidence.

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.

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.

Biomedical informatics as support to individual healthcare in hereditary colon cancer: the Danish HNPCC system.

The Danish HNPCC register is a publically financed national database. The register gathers epidemiological and genomic data in HNPCC families to improve prognosis by screening and identifying family members at risk. Diagnostic data are generated throughout the country and collected over several decades. Until recently, paper-based reports were sent to the register and typed into the database. In the EC cofunded-INFOBIOMED network of excellence, the register was a model for electronic exchange of epidemiological and genomic data between diagnosing/treating departments and the central database. The aim of digitization was to optimize the organization of screening by facilitating combination of genotype-phenotype information, and to generate IT-tools sufficiently usable and generic to be implemented in other countries and for other oncogenetic diseases. The focus was on integration of heterogeneous data, elaboration, and dissemination of classification systems and development of communication standards. At the conclusion of the EU project in 2007 the system was implemented in 12 pilot departments. In the surgical departments this resulted in a 192% increase of reports to the database. Several gaps were identified: lack of standards for data to be exchanged, lack of local databases suitable for direct communication, reporting being time-consuming and dependent on interest and feedback.

Hospital variation in 30-day mortality after colorectal cancer surgery in denmark: the contribution of hospital volume and patient characteristics.

OBJECTIVE: This study examines variation between hospitals in 30-day mortality after surgery for colorectal cancer (CRC) in Denmark and explores whether hospital volume and patient characteristics contribute to any variation between hospitals. BACKGROUND: Little is known about the variation between hospitals in 30-day mortality after CRC surgery, and the impact of treatment and patient characteristics that might contribute to such variation. METHODS: Hospital variation was quantified using a multilevel approach on data derived from a nationwide database of all adenocarcinomas of colon and rectum diagnosed in Denmark in 2001 to 2004. These data were linked to several central registers providing information on patient's socioeconomic status, comorbidity, and use of medication. In total 11,287 patients, who underwent surgery at any of the 43 surgical departments were included. RESULTS: Hospitals varied from 3.5% to 44.1% in 30-day mortality after emergency colon cancer surgery, and the multilevel analysis showed that emergency patients were 5 times [odd ratio (OR) = 4.6)] as likely to die within 30 days in hospitals with the worst performance compared to those with the best performance. The American Society of Anesthesiologists (ASA) score increased the variation between hospitals (OR = 5.8), whereas the other potential explanatory variables had no effect on the variation. For patients who had elective surgery for colon and rectal cancer the variation in 30-day mortality between hospitals was small and nonsignificant. CONCLUSION: Hospital variation in 30-day mortality after CRC surgery are due to differences in hospitals' ability to take care of emergency patients, especially those with high ASA scores.