Current Management of T1 Colon Cancer in Denmark: A Nationwide Cohort Study.

OBJECTIVE: To describe the management of T1 colon cancer in a retrospective study of a national cancer registry. BACKGROUND: There is increasing interest in the potential of local excision (LE) as an organ-preserving treatment for early colon cancer. However, accurate identification of patients who may have lymph node metastases (LNM) and require further surgery is a major challenge. METHODS: Patients diagnosed with T1 colon cancer in Denmark from 2016 to 2020 were included and divided according to treatment: polypectomy (referred to as LE), upfront colectomy and completion colectomy. Primary outcome was the proportion of patients diagnosed by LE. Secondary outcomes included the rate of LNM, the association of histopathological risk factors with LNM, and overall survival. RESULTS: 1,749 patients were included, and 1,022 patients (58.4%) underwent initial LE. The rate of R1 margins after initial LE was 31.0%. Colectomy was performed in 1,160 patients (upfront in 727, completion in 433), of whom 58.3% had pT1 cancer. The rate of LNM was 11.5%. Rates of LNM were similar in patients undergoing upfront or completion colectomy (10.2% vs 12.4%, P=0.392), and in patients with any single histopathological risk factor compared to those with none (8.9% vs 10.6%, P=0.565). Although overall survival was significantly shorter in patients undergoing LE alone, no association between survival and treatment strategy was found on multivariable analysis. CONCLUSIONS: LE is the most common mode of diagnosis in patients with T1 colon cancer and does not negatively impact survival and postoperative outcomes. Current strategies to stratify patients to completion surgery appear insufficient, and more robust predictors are needed.

Effect of colorectal cancer screening on colorectal cancer surgery outcomes: nationwide cohort study.

BACKGROUND: National colorectal cancer screening commenced in Denmark in 2014. Little is known about the effects of organized colorectal cancer screening on intraoperative and postoperative events. The aim of this nationwide cohort study was to evaluate the difference in intraoperative and postoperative outcomes between patients with screen-detected colorectal cancer and non-screen-detected colorectal cancer within the first 90 days after surgery. METHODS: National register data were collected for Danish residents diagnosed with colorectal cancer between January 2014 and March 2018. Outcomes for the two cohorts were reported as relative risk or weighted mean difference. Intraoperative outcomes were blood loss, blood transfusion, tumour perforation, and organ lesion. Postoperative outcomes were complications (surgical and non-surgical) and 90-day mortality. Discrete data estimates were calculated from a general linear model. Analyses were adjusted for potential healthy user bias with respect to sex, age, location of the cancer (colon/rectum), and Charlson co-morbidity index. RESULTS: In total, 10 606 patients were included. Compared with patients in the non-screen-detected colorectal cancer group (4497 patients), patients in the screen-detected colorectal cancer group (6109 patients) had reduced intraoperative blood loss (-52 mL, 95% c.i. -67 to -37, P < 0.001), a shorter duration of hospitalization (-2.3 days, 95% c.i. -2.8 to -1.8, P < 0.001), and reduced rates of intraoperative organ lesion (0.76, 95% c.i. 0.59 to 0.99, P = 0.042), surgical complications (0.79, 95% c.i. 0.73 to 0.87, P < 0.001), non-surgical complications (0.68, 95% c.i. 0.60 to 0.78, P < 0.001), and 90-day mortality (0.29, 95% c.i. 0.21 to 0.39, P < 0.001). CONCLUSION: In comparison with non-screen-detected colorectal cancer, surgery for screen-detected colorectal cancer remains associated with improvement in several intraoperative and early postoperative outcomes after considering healthy user bias.

Excessive Oxygen Administration in High-Risk Patients Admitted to Medical and Surgical Wards Monitored by Wireless Pulse Oximeter.

The monitoring of oxygen therapy when patients are admitted to medical and surgical wards could be important because exposure to excessive oxygen administration (EOA) may have fatal consequences. We aimed to investigate the association between EOA, monitored by wireless pulse oximeter, and nonfatal serious adverse events (SAEs) and mortality within 30 days. We included patients in the Capital Region of Copenhagen between 2017 and 2018. Patients were hospitalized due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD) or after major elective abdominal cancer surgery, and all were treated with oxygen supply. Patients were divided into groups by their exposure to EOA: no exposure, exposure for 1-59 min or exposure over 60 min. The primary outcome was SAEs or mortality within 30 days. We retrieved data from 567 patients for a total of 43,833 h, of whom, 63% were not exposed to EOA, 26% had EOA for 1-59 min and 11% had EOA for ≥60 min. Nonfatal SAEs or mortality within 30 days developed in 24%, 12% and 22%, respectively, and the adjusted odds ratio for this was 0.98 (95% CI, 0.96-1.01) for every 10 min. increase in EOA, without any subgroup effects. In conclusion, we did not observe higher frequencies of nonfatal SAEs or mortality within 30 days in patients exposed to excessive oxygen administration.

Coeliac disease in the Trøndelag Health Study (HUNT), Norway, a population-based cohort of coeliac disease patients.

PURPOSE: Coeliac disease (CD) is a common disorder and affects about 1% of the population worldwide. CD in the Trøndelag Health Study (HUNT) is a population-based cohort study which was established to provide new knowledge about CD that can improve the diagnostics and management, prevent the onset or progression and expand the knowledge about the role of genetics of the disease. PARTICIPANTS: The cohort is based on the fourth wave of the population-based HUNT study (HUNT4), Norway, performed during 2017-2019, also including linkage to hospital records and the Norwegian Patient Registry (NPR). A total of 54 541 HUNT4 participants with available sera were screened for CD by serology. All seropositive participants were invited to a clinical assessment, including endoscopy with duodenal biopsies, during 2019-2023. FINDINGS TO DATE: A total of 1107 HUNT4 participants (2%) were seropositive for CD and 1048 were eligible for clinical assessment, including biopsy. Of these, 724 participants attended the clinical assessment and 482 were identified with CD. In addition, 371 participants with CD were identified through the hospital records and NPR. In total, 853 participants in HUNT4 with biopsy-verified CD diagnosis were identified. FUTURE PLANS: All participants in the study will be invited to a follow-up assessment after at least 1 year, including repeated standard serological testing, endoscopy and tissue sampling. The collected data and material will be used to establish the true population-based prevalence of CD. The consequences of CD, including symptoms, deficiencies and comorbidity, will be investigated and possible triggers and predictors, will be studied. With access to serum samples from the previous HUNT surveys in HUNT Biobank, serological signs of CD in prediagnostic samples of seropositive individuals will be used. Genetic studies will identify new CD markers, assess genotype-phenotype links and explore gene-environment correlations. REGISTRATION: clinicaltrials.gov identifier: NCT04041622.

Frequency and risk factors of atrial fibrillation after acute abdominal surgery: A prospective cohort study.

BACKGROUND AND AIM: Scarce data exist on the true incidence of postoperative atrial fibrillation (POAF) after acute abdominal surgery and associated outcomes. The current study aimed to identify the frequencies of clinically recognized POAF and associated complications, along with their risk factors. METHODS: This study was a prospective, single-center cohort study of unselected adult patients referred for acute abdominal surgery during a 3-month period. Through careful review, demographics, comorbidity, and surgical characteristics were prospectively drawn from medical charts. The primary outcome was clinically recognized POAF occurring in-hospital. Logistic regression was used to determine the risk factors of POAF and associated complications. A subgroup was enrolled in a feasibility study of peri- and postoperative continuous cardiac rhythm monitoring. RESULTS: In total, 450 patients were enrolled. Clinically recognized in-hospital POAF was observed in 22 patients (4.9%). All cases were observed in patients aged ≥60 years, corresponding to 22 of 164 patients (13.4%). Multiple risk factors were observed, such as age, prior atrial fibrillation, heart failure, hypertension, diabetes mellitus, chronic renal disease, and major (vs. minor) surgery. POAF was associated with severe in-hospital complications (POAF group 45.5% vs. non-POAF group 8.6%, p < .001) and in-hospital mortality (POAF group 13.6% vs. non-POAF group 3.0%, p = .043). In total, 295 patients were monitored by continuous cardiac rhythm monitoring for 12,148 h, yielding five patients with asymptomatic AF. CONCLUSIONS: In conclusion, this prospective study of POAF in patients undergoing acute abdominal surgery showed that one in 20 patients developed clinically recognized in-hospital POAF. Multiple risk factors of POAF were identified. POAF was associated with severe complications up to 30 days after surgery.

Preoperative multimodal prehabilitation before elective colorectal cancer surgery in patients with WHO performance status I or II: randomized clinical trial.

BACKGROUND: Multimodal prehabilitation is a promising adjunct to the current surgical treatment pathway for colorectal cancer patients to further improve postoperative outcomes, especially for high-risk patients with low functional capacity. The aim of the present study was to test the effect of prehabilitation on immediate postoperative recovery. METHOD: The study was designed as a RCT with two arms (intervention and control). The intervention consisted of 4 weeks of multimodal prehabilitation, with supervised physical training, nutritional support and medical optimization. The control group received standard of care. A total of 40 patients with colorectal cancer (WHO performance status I or II) undergoing elective surgery with curative intent were included. The primary outcome was postoperative recovery within the first 3 postoperative days, measured by Quality of Recovery-15, a validated questionnaire with a scoring range between 0 and 150 and a minimal clinically relevant difference of 8. RESULTS: In total, 36 patients were analysed with 16 in the intervention group and 20 in the control group. The mean age of the included patients was 79 years. The overall treatment effect associated with the intervention was a 21.9 (95% c.i. 4.5-39.3) higher quality of recovery-15 score during the first 3 postoperative days compared to control, well above the minimal clinically relevant difference. CONCLUSION: Four weeks of multimodal prehabilitation prior to elective curative intended colorectal cancer surgery in patients with WHO performance status I or II was associated with a clinically relevant improvement in postoperative recovery.Registration number: NCT04167436 (http://www.clinicaltrials.gov).

Nurse navigation, symptom monitoring and exercise in vulnerable patients with lung cancer: feasibility of the NAVIGATE intervention.

We developed the Navigate intervention to improve survival among vulnerable lung cancer patients. In this intervention-only study, we examined feasibility in terms of recruitment, retention, attendance, adherence, and acceptability to specify adjustments to study procedures and intervention components prior to a randomized trial. The Navigate intervention includes nurse navigation, patient-reported outcomes, and physical exercise. Patients ≥ 18 years old, diagnosed with non-small cell lung cancer at any stage, with performance status ≤ 2, eligible for cancer treatment and vulnerable according to a screening instrument were included. The recruitment goal of eligible patients was 40% while the retention goal was 85%. The predefined cut-offs for sufficient attendance and adherence were ≥ 75%. Acceptability was evaluated by semi-structured interviews with participants, nurse navigators, and physiotherapists. Seventeen (56%) out of 30 screened patients were considered vulnerable and eligible for the study, 14 (82%) accepted participation, and 3 (21%) were subsequently excluded due to ineligibility, leaving 11 patients. Four patients dropped out (36%) and four patients died (36%) during follow-up and 3 (27%) were retained. All 11 patients participated in nurse sessions (mean 16, range 1-36) with 88% attendance and dialogue tools being applied in 68% of sessions. Ninety-one percent of patients responded to PROs (mean of 9 PROs, range 1-24) with 76% of the PRO questionnaires used (attendance) and 100% adherence (completion of all questions in PRO questionnaires), and 55% participated in exercise sessions with 58% attendance and 85% adherence. We identified important barriers primarily related to transportation, but overall acceptability was high. The Navigate intervention was feasible with high participation, acceptability and satisfactory adherence. Retention and exercise attendance were low, which resulted in adjustments.Trial registration: The feasibility study was initiated prior to the multicenter randomized controlled trial registered by ClinicalTrials.gov (number: NCT05053997; date 23/09/2021).

The impact of anemia and blood transfusion on mortality after open abdominal surgery in the elderly.

BACKGROUND: Major abdominal surgery is associated with considerable mortality in the elderly. Anemia has been linked to increased mortality in other types of surgery, such as hip and cardiac surgery. This study aimed to assess the impact of preoperative anemia on mortality in the elderly undergoing major abdominal surgery, and how allogeneic red cell blood transfusion influences mortality in these patients. MATERIALS AND METHODS: We conducted a single-center, register-based retrospective study on patients, who were aged beyond 60 years and underwent one of 81 open abdominal surgical procedures. Patients operated on during the period from January 1, 2000, to May 31, 2013, were consecutively identified in the Danish National Patient Registry. Plasma hemoglobin was measured within 30 days prior to surgery and the primary endpoint was 30-day postoperative mortality. Information about patient transfusions from the hospital blood bank was available from 1998 to 2010. RESULTS: A total of 3199 patients were included of whom 85% underwent emergency surgery. The total mortality after 30 days was 20%. The median preoperative hemoglobin value of survivors was 7.7 mmol/L vs 6.9 mmol/L in those who died. The difference in hemoglobin values, between those who survived or died, decreased from the pre- to the post-operative phase. The 30-day postoperative mortality was 28%, 20%, and 12% in patients with a preoperative hemoglobin level in the lower, median, and upper quartile respectively. Transfusion therapy was associated with higher postoperative mortality, except in patients with very low hemoglobin values. CONCLUSION: Preoperative anemia has a clear association with surgically related mortality. The distribution of hemoglobin values in patients with a fatal outcome differs significantly from that of survivors. Red cell transfusion is associated with increased mortality, except in patients with very low hemoglobin values which supports recent guidelines suggesting a restrictive transfusion strategy.

Risk of Cancer in Patients With Crohn's Disease 30 Years After Diagnosis (the IBSEN Study).

Background: Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types. Methods: The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population. Results: In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively). Conclusions: After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.

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

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

Neo-train: study protocol and feasibility results for a two-arm randomized controlled trial investigating the effect of supervised exercise during neoadjuvant chemotherapy on tumour response in patients with breast cancer.

BACKGROUND: Prehabilitation with exercise interventions during neoadjuvant chemotherapy (NACT) is effective in reducing physical and psychosocial chemotherapy-related adverse events in patients with cancer. In preclinical studies, data also support a growth inhibitory effect of aerobic exercise on the tumour microenvironment with possible improved chemotherapy delivery but evidence in human patients is limited. The aim of the study here described is to investigate if supervised exercise with high-intensity aerobic and resistance training during NACT can improve tumour reduction in patients with breast cancer. METHODS: This parallel two-armed randomized controlled trial is planned to include 120 women aged ≥ 18 years with newly diagnosed breast cancer starting standard NACT at a university hospital in Denmark (a total of 90 participants needed according to the power calculation and allowing 25% (n = 30) dropout). The participants will be randomized to usual care or supervised exercise consisting of high-intensity interval training on a stationary exercise bike and machine-based progressive resistance training offered three times a week for 24 weeks during NACT, and screening-based advice to seek counselling in case of moderate-severe psychological distress (Neo-Train program). The primary outcome is tumour size change (maximum diameter of the largest lesion in millimetre) measured by magnetic resonance imaging prior to surgery. Secondary outcomes include clinical/pathological, physical and patient-reported measures such as relative dose intensity of NACT, hospital admissions, body composition, physical fitness, muscle strength, health-related quality of life, general anxiety, depression, and biological measures such as intratumoural vascularity, tumour infiltrating lymphocytes, circulating tumour DNA and blood chemistry. Outcomes will be measured at baseline (one week before to 1-2 weeks after starting NACT), during NACT (approximately week 7, 13 and 19), pre-surgery (approximately week 21-29), at surgery (approximately week 21-30) and 3 months post-surgery (approximately 33-42 weeks from baseline). DISCUSSION: This study will provide novel and important data on the potential benefits of supervised aerobic and resistance exercise concomitant to NACT on tumour response and the tumour microenvironment in patients with breast cancer, with potential importance for survival and risk of recurrence. If effective, our study may help increase focus of exercise as an active part of the neoadjuvant treatment strategy. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT04623554) on November 10, 2020.

Incidence of cancer in patients with ulcerative colitis 30 years after diagnosis (the IBSEN study).

OBJECTIVES: Patients with ulcerative colitis (UC) have shown an increased risk for colorectal cancer, hepatobiliary, hematologic, and skin cancers, but updated long-term data is needed. This study aimed to estimate the risk of cancer in patients with UC compared to the general Norwegian population, in a population-based cohort (the IBSEN study), 30 years after diagnosis; and to identify possible risk factors associated with cancer. METHODS: The IBSEN cohort prospectively included all incident patients between 1990 and 1993. Cancer incidence data were obtained from the Cancer Registry of Norway. The overall and cancer-specific hazard ratios (HR) were modelled using Cox regression. Standardized incidence ratios were estimated compared to the general population. RESULTS: In total, the cohort included 519 patients, and 83 cases were diagnosed with cancer. There was no statistically significant difference in the overall cancer risk (HR = 1.01, 95% CI: [0.79-1.29]) and colorectal cancer risk (HR = 1.37, 95% CI: [0.75-2.47]) between patients and controls. The incidence of biliary tract cancer was higher than expected (SIR = 9.84, 95%CI: [3.19-20.15]), especially when UC patients suffered from primary sclerosing cholangitis. Male UC patients were also more at risk of being diagnosed with hematologic malignancies (HR = 3.48, 95% CI: [1.55-7.82]). Being prescribed thiopurines was associated with a higher risk of cancer (HR = 2.03, 95% CI: [1.02-4.01]). CONCLUSIONS: At 30 years after diagnosis, the risk of all cancer in patients with UC was not significantly increased compared with the general population. However, the risks of biliary tract cancer and hematologic cancers were increased, particularly in male patients.

Fatigue in Patients with Newly Diagnosed Inflammatory Bowel Disease: Results from a Prospective Inception Cohort, the IBSEN III Study.

BACKGROUND AND AIMS: Although fatigue is common in inflammatory bowel disease [IBD], its pathogenesis remains unclear. This study aimed to determine the prevalence of fatigue and its associated factors in a cohort of patients newly diagnosed with IBD. METHODS: Patients ≥18 years old were recruited from the Inflammatory Bowel Disease South-Eastern Norway [IBSEN III] study, a population-based, observational inception cohort. Fatigue was assessed using the Fatigue Questionnaire and compared with data from a Norwegian general population. Univariate and multivariate linear and logistic regression analyses were performed to evaluate the associations of total fatigue [TF; continuous score] and substantial fatigue [SF; dichotomized score ≥4] with sociodemographic, clinical, endoscopic, laboratory, and other relevant patient data. RESULTS: In total, 983/1509 [65.1%] patients with complete fatigue data were included (ulcerative colitis [UC], 68.2%; Crohn's disease [CD], 31.8%). The prevalence of SF was higher in CD [69.6%] compared with UC [60.2%] [p < 0.01], and in both diagnoses when compared to the general population [p < 0.001]. In multivariate analyses, depressive symptoms, pain intensity, and sleep disturbances were associated with increased TF for both diagnoses. In addition, increased clinical disease activity and Mayo endoscopic score were significantly associated with TF in UC, whereas all disease-related variables were insignificant in CD. Similar findings were observed for SF, except regarding the Mayo endoscopic score. CONCLUSIONS: SF affects approximately two-thirds of patients newly diagnosed with IBD. Fatigue was associated with depressive symptoms, sleep disturbances, and increased pain intensity in both diagnoses, while clinical and endoscopic activity were associated factors only in UC.

Health-related quality of life in patients with newly diagnosed inflammatory bowel disease: an observational prospective cohort study (IBSEN III).

PURPOSE: This unselected, population-based cohort study aimed to determine the level of health-related quality of life (HRQoL) in patients with Crohn's disease (CD) and ulcerative colitis (UC) at the time of diagnosis compared with a reference population and identify the demographic factors, psychosocial measures, and disease activity markers associated with HRQoL. METHODS: Adult patients newly diagnosed with CD or UC were prospectively enrolled. HRQoL was measured using the Short Form 36 (SF-36) and Norwegian Inflammatory Bowel Disease Questionnaires. Clinical significance was assessed using Cohen's d effect size and further compared with a Norwegian reference population. Associations between HRQoL and symptom scores, demographic factors, psychosocial measures, and disease activity markers were analyzed. RESULTS: Compared with the Norwegian reference population, patients with CD and UC reported significantly lower scores in all SF-36 dimensions, except for physical functioning. Cohen's d effect sizes for men and women in all SF-36 dimensions were at least moderate, except for bodily pain and emotional role for men with UC and physical functioning for both sexes and diagnoses. In the multivariate regression analysis, depression subscale scores ≥ 8 on the Hospital Anxiety and Depression Scale, substantial fatigue, and high symptom scores were associated with reduced HRQoL. CONCLUSION: Patients newly diagnosed with CD and UC reported statistically and clinically significantly lower scores in seven of the eight SF-36 dimensions than the reference population. Symptoms of depression, fatigue, and elevated symptom scores were associated with poorer HRQoL.

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden.

BACKGROUND: Fecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. MATERIALS AND METHODS: From the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. RESULTS: The discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. CONCLUSION: A screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

High serum levels of the C-propetide of type V collagen (PRO-C5) are prognostic for short overall survival in patients with pancreatic ductal adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a pronounced fibrotic tumor microenvironment, which impairs treatment response. Type I and V collagens are responsible for the densely packed fibrils in the tumor fibrosis environment. While the role of the major type I collagen in cancer is well described, less is known about the minor type V collagen. Quantifying collagen propeptides in serum has been shown to have prognostic and predictive value. In this study, we evaluated the clinical utility of measuring the propeptide of type V collagen (PRO-C5) in serum from a discovery cohort and a validation cohort of patients with PDAC as well as in non-pancreatic solid tumor types to explore the relevance of the PRO-C5 biomarker in cancer. Methods: Serum PRO-C5 was measured in three cohorts: a discovery cohort (19 healthy controls, 12 patients with chronic pancreatitis and 33 patients with PDAC (stage I-IV)), a validation cohort (800 patients with PDAC (stage I-IV)), and a non-pancreatic solid tumor type cohort of 33 healthy controls and 200 patients with 10 different non-pancreatic solid tumor types. The levels of serum PRO-C5 in patients with cancer were compared to levels in healthy controls. The association between PRO-C5 levels and overall survival (OS) was evaluated in patients with PDAC after adjusting for established prognostic factors. Results: PRO-C5 was significantly increased in serum from patients with PDAC compared to healthy controls (p < 0.001). High PRO-C5 levels were significantly associated with short OS in both the discovery- and the validation cohort, especially in early stages of PDAC (validation cohort stage II, HR = 2.0, 95%CI1.2-3.4). The association was independent of other prognostic parameters including stage, performance status and CA19-9. Furthermore, serum levels of PRO-C5 were significantly increased in serum from patients with other non-pancreatic solid tumor types compared to healthy controls. Conclusion: High levels of serum PRO-C5 is prognostic for short OS in patients with PDAC and may provide clinical value in many other tumor types beyond PDAC. This underlines the importance of type V collagen in tumor fibrosis. PRO-C5 could have the potential to be used in several aspects within drug discovery, patient stratification and drug efficacy.

Barriers for Participation in the Danish Colorectal Cancer Screening Program: a Qualitative Study.

PURPOSE: The participation rate in the Danish National Screening Program for Colorectal Cancer is around 60%. Since early detection of cancer through the colorectal cancer screening program (CRCS) reduces mortality rates, it is important to understand why people do not participate. The aim of this study was therefore to examine in depth why some people do not participate in the Danish CRCS program. METHODS: Individual semi-structured interviews were conducted with 18 people who had not participated in the national CRCS program. Data was analyzed using an inductive hermeneutic approach. RESULTS: The analysis uncovered three main themes describing barriers to screening: (a) the accountability for ensuring personal health covered the following sub-themes: (i) when invitation is out of sight it is out of mind, (ii) aversion against own stool sample collection, and (iii) the perceived risk of getting colorectal cancer (CRC); (b) attitudes towards the healthcare system and its organization covered the following sub-themes: (i) positivity towards CRCS, (ii) trust in the healthcare system, (iii) lack of internal communication in the healthcare system, and (iv) wish for involvement of the general practitioner (GP); (c) knowledge about disease and screening covered the following sub-themes: (i) knowledge about CRC and CRCS, (ii) wish for information via new channels, and (iii) CRC is rarely something you talk about. CONCLUSION: Among the informants included in this study, lack of participation in the CRCS program was not due to an active opt-out, as most informants had intentions of participating. The informants thought it would motivate them to participate if their GP would remind them of the screening program.

Mortality in Patients with Inflammatory Bowel Disease: Results from 30 Years of Follow-up in a Norwegian Inception Cohort (the IBSEN study).

BACKGROUND AND AIMS: Patients with longstanding inflammatory bowel disease [IBD] may be at an increased risk of death compared to the general population, especially elderly patients. The Inflammatory Bowel South-Eastern Norway [IBSEN] study has previously detected a small but not statistically significant increase in mortality 20 years after diagnosis. The aim of this study was to evaluate the overall and cause-specific mortality at 30 years of follow-up. METHODS: The IBSEN cohort included 519 incident patients with ulcerative colitis [UC] and 237 patients with Crohn's disease [CD] between 1990 and 1993, each matched with five controls. Death certificate data were obtained from the Norwegian Cause of Death Registry. The underlying causes of death were categorized into five groups: all cancers, gastrointestinal cancers, cardiovascular diseases, infections and all other causes. Hazard ratios [HRs] were modelled using Cox regression. RESULTS: There was no statistically significant difference in the overall mortality rates. However, in patients with CD, male sex (HR = 1.65 [95% CI: 1.04-2.62]), onset after 40 years of age (HR = 1.72 [1.19-2.48]), colonic disease (HR = 1.57 [1.05-2.35]) and penetrating behaviour (HR = 3.3 [1.41-7.76]) were clinical factors associated with an increased mortality. IBD patients were at a higher risk of death due to cardiovascular disease: HR = 1.51 [1.10-2.08] for UC and 2.04 [1.11-3.77] for CD. When taking into account both the underlying and the immediate cause of death, infection was more frequent in patients with IBD. CONCLUSIONS: Overall, all-cause mortality rates were similar between patients with IBD and controls. However, clinicians should remain alert to cardiovascular diseases and infections, particularly in specific subgroups of CD patients.

Endoscopic Anterior Component Separation and Transversus Abdominus Release are not Associated with Increased Wound Morbidity Following Retromuscular Incisional Hernia Repair.

INTRODUCTION: Traditional anterior component separation during incisional hernia repair (IHR) is associated with a high rate of postoperative wound morbidity. Because extensive subcutaneous dissection is avoided by endoscopic anterior component separation (eACS) or open transversus abdominis release (TAR), we hypothesized that these techniques did not increase the incidence of surgical site occurrence (SSO) compared to IHR without component separation (CS). MATERIAL AND METHOD: This was a retrospective single-center cohort study of patients undergoing open retromuscular IHR comparing patients with or without the use of CS. Retromuscular mesh repair was performed in all patients, and CS was obtained by eACS or TAR. The primary outcome was 90-day incidence of postoperative SSO. Secondary outcomes included length of stay (LOS), 90-day readmission, 90-day reoperation rate and 3-year recurrence rate. RESULTS: A total of 321 patients underwent retromuscular repair, 168 (52.3%) of whom received either eACS or TAR. The addition of eACS or TAR was associated neither with development of SSO (odds ratio: 1.80, 95% confidence interval: 0.94-3.46, P = 0.077) nor with hernia recurrence (hazard ratio 0.77, 0.26-2.34, P = 0.648). There was no significant difference between the groups regarding the frequencies of 90-day readmission or 90-day reoperation. CONCLUSION: eACS or TAR as adjuncts to open retromuscular IHR were not associated with increased wound morbidity or hernia recurrence.