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1.
Dis Colon Rectum ; 64(5): 583-591, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33939389

RESUMO

BACKGROUND: Patients undergoing total colectomy for IBD may develop cancer in the rectal remnant, but the association is poorly understood. OBJECTIVES: This study aimed to examine the risk and prognosis of rectal cancer after total colectomy for IBD. DESIGN: This is a nationwide population-based study. SETTING: Treatment of the patients took place in Denmark from 1977 to 2013. PATIENTS: Patients with IBD undergoing total colectomy were included. MAIN OUTCOME MEASURES: We examined the incidence of rectal cancer among patients with IBD and total colectomy and compared cancer stage to that of other patients with rectal cancer in Denmark. We used Kaplan-Meier methodology to estimate survival and Cox regression to estimate adjusted mortality rate ratios following a rectal cancer diagnosis, comparing patients with and without IBD and a rectal remnant. RESULTS: We identified 4703 patients with IBD (1026 Crohn's disease; 3677 ulcerative colitis) who underwent total colectomy with a rectal remnant. During 29,725 years of follow-up, 30 rectal cancers were observed, compared with 8 rectal cancers expected (standardized incidence ratio = 3.6 (95% CI, 2.4-5.1)). Cancer stage distributions were similar. Risk of rectal cancer 35 years after total colectomy was 1.9% (95% CI, 1.1%-2.9%). Five years after rectal cancer diagnosis, survival was 28% (95% CI, 12%-47%) and 38% (95% CI, 37%-38%) for patients with and without IBD and a rectal remnant. The adjusted mortality rate ratio 1 to 5 years after a rectal cancer diagnosis was 2.5 (95% CI, 1.6-3.9). Median time from last recorded nondiagnostic proctoscopy to rectal cancer diagnosis for patients with IBD and total colectomy was 1.1 years. LIMITATIONS: This study was limited by the few outcomes and the use of administrative and not clinical data. CONCLUSION: Long-term risk of rectal cancer following total colectomy for IBD was low. Survival following a diagnosis of rectal cancer was poorer for patients with IBD and total colectomy than for patients who had rectal cancer without IBD and total colectomy. Endoscopic surveillance, as it appeared to be practiced in this cohort, may be inadequate. See Video Abstract at http://links.lww.com/DCR/B497. RIESGO DE CÁNCER DE RECTO Y SUPERVIVENCIA DESPUÉS DE UNA COLECTOMÍA TOTAL POR ENFERMEDAD INFLAMATORIA INTESTINAL: UN ESTUDIO POBLACIONAL: Los pacientes sometidos a colectomía total por enfermedad inflamatoria intestinal (EII) pueden desarrollar cáncer en el remanente rectal, pero la asociación es poco conocida.Examinar el riesgo y el pronóstico del cáncer de recto después de una colectomía total para la EII.Estudio poblacional a nivel nacional.Dinamarca 1977-2013.Pacientes con EII sometidos a colectomía total.Examinamos la incidencia de cáncer de recto entre pacientes con EII y colectomía total y comparamos el estadio del cáncer con el de otros pacientes con cáncer de recto en Dinamarca. Utilizamos la metodología de Kaplan-Meier para estimar la supervivencia y la regresión de Cox para estimar las tasas de mortalidad ajustadas (aMRR) después de un diagnóstico de cáncer de recto, comparando pacientes con y sin EII y un remanente rectal.Identificamos 4.703 pacientes con EII (1.026 enfermedad de Crohn; 3.677 colitis ulcerosa) que se sometieron a colectomía total con remanente rectal. Durante 29,725 años de seguimiento, se observaron 30 cánceres de recto, en comparación con los 8 esperados [razón de incidencia estandarizada (SIR) = 3.6, (intervalo de confianza (IC) del 95%: 2.4-5.1)]. Las distribuciones de las etapas del cáncer fueron similares. El riesgo de cáncer de recto 35 años después de la colectomía total fue del 1,9% (IC del 95%: 1,1% -2,9%). Cinco años después del diagnóstico de cáncer de recto, la supervivencia fue del 28% (IC del 95%: 12% -47%) y del 38% (IC del 95%: 37% -38%) para los pacientes con y sin EII y un remanente rectal, respectivamente. La aMRR 1-5 años después de un diagnóstico de cáncer de recto fue de 2,5 (IC del 95%: 1,6-3,9). La mediana de tiempo desde la última proctoscopia no diagnóstica registrada hasta el diagnóstico de cáncer de recto en pacientes con EII y colectomía total fue de 1,1 años.Pocos resultados, uso de datos administrativos y no clínicos.El riesgo a largo plazo de cáncer de recto después de una colectomía total para la EII fue bajo. La supervivencia después de un diagnóstico de cáncer de recto fue más pobre para los pacientes con EII y colectomía total que para los pacientes con cáncer de recto sin EII y colectomía total. La vigilancia endoscópica, como parecía practicarse en esta cohorte, puede ser inadecuada. Consulte Video Resumen en http://links.lww.com/DCR/B497. (Traducción-Dr. Adrian Ortega).

2.
Cancer Epidemiol Biomarkers Prev ; 30(5): 886-894, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33627380

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with hepatobiliary cancer, but existing evidence is poor. We evaluated risk of death from hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), and extrahepatic cholangiocarcinoma (ECC) among patients with IBD. METHODS: This Swedish/Danish population-based cohort study (1969-2017) followed patients with IBD and 1:10 matched population comparators from their diagnosis/match date until death, emigration, or end of follow-up. RESULTS: Among the 97,496 patients with ulcerative colitis/963,026 comparators, we found 66/390 HCC-deaths, 120/173 ICC-deaths, and 91/220 ECC-deaths (median follow-up 10 years); the 10-year-mortality was 0.5‰ (per mille) for HCC, 0.6‰ for ICC, and 0.4‰ for ECC, which decreased to 0.3‰, 0.4‰, and 0.2‰, respectively, in 2003-2017. Overall hazard ratios (HR) were 1.83 [95% confidence interval (CI), 1.41-2.38] for HCC-, 7.33 (95% CI, 5.81-9.25) for ICC-, and 4.46 (95% CI, 3.49-5.70) for ECC-deaths. A total of 22/66 HCC-deaths, 87/120 ICC-deaths, and 55/91 ECC-deaths occurred among patients with ulcerative colitis with primary sclerosing cholangitis (PSC), corresponding to 10-year-mortality of 6.7‰, 26.2‰, and 17.2‰, respectively. Among 47,399 patients with Crohn's disease (median follow-up 11 years), 10-year-mortality from HCC (n = 28), ICC (n = 28), and ECC (n = 24) were 0.3‰, 0.1‰, and 0.3‰, respectively, and corresponding HRs were 1.96 (95% CI, 1.31-2.93), 3.33 (95% CI, 2.19-5.09), and 3.10 (95% CI, 1.97-4.87). One of 28 HCC-deaths, 14/28 ICC-deaths (10-year-mortality 19‰), and 12/24 ECC-deaths (10-year-mortality 14‰) occurred after PSC. CONCLUSIONS: Risk of HCC-, ICC-, and ECC-deaths was low in patients with IBD and decreased over time. However, a large proportion of deaths occurred after PSC. IMPACT: Guidelines on specific surveillance strategies for patients with IBD with PSC, but not those without PSC, are needed.

3.
Pharmacoepidemiol Drug Saf ; 30(6): 770-778, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33583126

RESUMO

BACKGROUND: Statins exert pleiotropic anti-inflammatory effects and may prevent diverticular disease. However, the association remains poorly understood with previous studies obtaining conflicting results. AIMS: To examine the effect of statin on the subsequent risk of diverticular disease. METHODS: We conducted a nested case-control study in Denmark among respondents (>18 years) of the 2010 or the 2013 Danish National Health Survey. Among these, we identified 8809 cases of hospital-diagnosed diverticular disease and risk-set sampled population controls without diverticular disease. Using complete prescription and hospital records, we used conditional logistic regression to compute odds ratios (ORs) associating statin use with diverticular disease. In adjusted analyses, we controlled for hospital-based diagnoses, medication use other than statins, and lifestyle and socioeconomic factors. RESULTS: The fully adjusted OR for diverticular disease associated with ever use (≥1 statin prescription filling) was 1.19 (95% CI: 1.12-1.27) compared with never use. However, we observed no dose-response relation. For example, among short-term users (<5 years), the OR was 1.18 (95% CI: 1.04-1.35) for low intensity users and 1.13 (95% CI: 1.01-1.26) for high intensity users. Among long-term users (≥5 years), the respective ORs were 1.25 (95% CI: 1.13-1.38) and 1.11 (95% CI: 0.98-1.24). In analyses restricting to cases and controls with a previous colonoscopy, associations were null (OR: 1.01 [95% CI: 0.85-1.20]). CONCLUSIONS: The observed association of a higher risk of diverticular disease associated with statins could be explained by diagnostic bias. Our study did not support a protective nor harmful effect of statins on the risk of diverticular disease.

4.
Dis Colon Rectum ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33496488

RESUMO

BACKGROUND: Patients undergoing total colectomy for inflammatory bowel disease (IBD) may develop cancer in the rectal remnant, but the association is poorly understood. OBJECTIVES: To examine risk and prognosis of rectal cancer after total colectomy for IBD. DESIGN: Nationwide population-based study. SETTING: Denmark 1977-2013. PATIENTS: Patients with IBD undergoing total colectomy. MAIN OUTCOME MEASURES: We examined incidence of rectal cancer among patients with IBD and total colectomy and compared cancer stage to that of other rectal cancer patients in Denmark. We used Kaplan-Meier methodology to estimate survival and Cox regression to estimate adjusted mortality rate ratios (aMRRs) following a rectal cancer diagnosis, comparing patients with and without IBD and a rectal remnant. RESULTS: We identified 4,703 patients with IBD (1,026 Crohn's disease; 3,677 ulcerative colitis) who underwent total colectomy with a rectal remnant. During 29,725 years of follow-up, 30 rectal cancers were observed, compared to 8 expected [standardized incidence ratio (SIR)=3.6, (95% confidence interval (CI): 2.4-5.1)]. Cancer stage distributions were similar. Risk of rectal cancer 35 years after total colectomy was 1.9% (95% CI:1.1%-2.9%). Five years after rectal cancer diagnosis, survival was 28% (95% CI: 12%-47%) and 38% (95% CI: 37%-38%) for patients with and without IBD and a rectal remnant, respectively. The aMRR 1-5 years after a rectal cancer diagnosis was 2.5 (95% CI: 1.6-3.9). Median time from last recorded non-diagnostic proctoscopy to rectal cancer diagnosis for patients with IBD and total colectomy was 1.1 years. LIMITATIONS: Few outcomes, use of administrative and not clinical data. CONCLUSION: Long-term risk of rectal cancer following total colectomy for IBD was low. Survival following a diagnosis of rectal cancer was poorer for patients with IBD and total colectomy than for rectal cancer patients without IBD and total colectomy. Endoscopic surveillance, as it appeared to be practiced in this cohort, may be inadequate. See Video Abstract at http://links.lww.com/DCR/B497 .

5.
Endoscopy ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33241540

RESUMO

BACKGROUND AND STUDY AIMS: Post-colonoscopy colorectal cancers (PCCRCs) may account for up to 50% of all colorectal cancers (CRCs) diagnosed in patients with inflammatory bowel disease (IBD). This may reflect a high colonoscopy frequency; however evidence remains limited. PATIENT AND METHODS: We conducted a cohort study of IBD and non-IBD patients undergoing colonoscopy. We calculated 6-36 months CIPs of PCCRC after first-time and subsequent colonoscopies. We also computed crude and adjusted HRs of PCCRC, comparing IBD with non-IBD patients undergoing first-time and subsequent colonoscopies. Separate analyses were conducted for consecutive colonoscopies. We calculated PCCRC-3 year rates to estimate the proportion of IBD and non-IBD CRC patients experiencing PCCRC. RESULTS: We observed 138 and 1,909 PCCRCs among 34,688 IBD and 358,217 non-IBD patients who underwent colonoscopy. The CIP of PCCRC after first-time colonoscopy was 0.21%, 95% confidence interval (CI): [0.17-0.27] for IBD patients and 0.37%, 95% CI: [0.35-0.39] for non-IBD patients. The adjusted HR of PCCRC after a first-time colonoscopy was 0.96, 95% CI: [0.75-1.22] and the adjusted HRs after subsequent colonoscopies had point estimates around 1.0. The PCCRC-3 year rate was 24.3%, 95% CI: [20.4-28.7] for IBD and 7.5%, 95% CI [7.2-7.8] for non-IBD patients. CONCLUSIONS: Although PCCRCs accounted for a substantial proportion of all IBD-related CRCs, IBD patients had a low CIP of PCCRC after colonoscopy. The elevated PCCRC-3 year rates may among other factors stem from increased colonoscopy frequency in IBD patients.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32719046

RESUMO

OBJECTIVE: Aspirin may increase the risk of lower gastrointestinal bleeding (LGIB) from precursors of colorectal cancer (CRC). We investigated whether use of low-dose aspirin, through initiation of LGIB, may lead patients to undergo colonoscopy and polypectomy before manifest CRC. DESIGN: We conducted a historical cohort study (2005-2013) of all Danish residents who initiated low-dose aspirin treatment (n=412 202) in a setting without screening for CRC. Each new aspirin user was matched with three non-users (n=1 236 560) by age, sex and region of residence on the date of their matched new user's first-time aspirin prescription (index date). We computed absolute risks (ARs), risk differences and relative risks (RRs) of LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC, comparing aspirin users with non-users. RESULTS: The ARs were higher for new users than non-users for LGIB, lower gastrointestinal endoscopy, colorectal polyps and CRC within 3 months after index. Comparing new users with non-users, the RRs were 2.79 (95% CI 2.40 to 3.24) for LGIB, 1.73 (95% CI 1.63 to 1.84) for lower gastrointestinal endoscopy, 1.56 (95% CI 1.42 to 1.72) for colorectal polyps and 1.73 (95% CI 1.51 to 1.98) for CRC. The RRs remained elevated for more than 12 months after the index date, with the exception of CRC where the RRs were slightly decreased during the 3-5 years (RR 0.90, 95% CI 0.83 to 0.98) and more than 5 years (RR 0.91, 95% CI 0.82 to 1.00) following the index date. CONCLUSION: These findings indicate that aspirin may contribute to reduce CRC risk by causing premalignant polyps to bleed, thereby expediting colonoscopy and polypectomy before CRC development.

8.
Gut ; 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32474410

RESUMO

OBJECTIVE: Crohn's disease (CD) is associated with increased risk of small bowel cancer (SBC), but previous studies have been small. We aimed to examine the risk of incident SBC and death from SBC in patients with inflammatory bowel disease (IBD). DESIGN: In a binational, population-based cohort study from Sweden and Denmark of patients with IBD during 1969-2017 and matched reference individuals from the general population, we evaluated the risk of incident SBC and death from SBC. Cox regression was used to estimate adjusted hazard ratios (aHRs). RESULTS: We identified 161 896 individuals with IBD (CD: 47 370; UC: 97 515; unclassified IBD: 17 011). During follow-up, 237 cases of SBC were diagnosed in patients with IBD (CD: 24.4/100 000 person-years; UC: 5.88/100 000 person-years), compared with 640 cases in reference individuals (2.81/100 000 person-years and 3.32/100 000 person-years, respectively). This corresponded to one extra case of SBC in 385 patients with CD and one extra case in 500 patients with UC, followed up for 10 years. The aHR for incident SBC was 9.09 (95% CI 7.34 to 11.3) in CD and 1.85 (95% CI 1.43 to 2.39) in UC. Excluding the first year after an IBD diagnosis, the aHRs for incident SBC decreased to 4.96 in CD and 1.69 in UC. Among patients with CD, HRs were independently highest for recently diagnosed, childhood-onset, ileal and stricturing CD. The relative hazard of SBC-related death was increased in both patients with CD (aHR 6.59, 95% CI 4.74 to 9.15) and patients with UC (aHR 1.57; 95% CI 1.07 to 2.32). CONCLUSION: SBC and death from SBC were more common in patients with IBD, particularly among patients with CD, although absolute risks were low.

9.
Cancer Epidemiol ; 66: 101725, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32353773

RESUMO

BACKGROUND: Biologic and epidemiologic evidence suggests that tumor cells depend on reprogrammed lipid metabolic function for survival and growth. Lipids may promote tumor recurrence by providing energy needed for proliferation. Studies have found associations of serum lipids with cancer incidence, mortality, and disease-free mortality, though they have yet to evaluate the prognostic potential of serum lipids for colorectal cancer (CRC) recurrence. METHODS: 341 Danish CRC patients who underwent surgical resection were actively followed between 2003-2011 from date of surgery until December 31, 2012, or death. Serum lipids including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were collected at regular intervals. Lipids were assigned as time-varying exposures evaluated with a one-year lag. Cox proportional hazards models were used to assess recurrence rate, adjusting for clinically relevant covariates. A restricted analysis was performed in a group of non-statin users (n = 236). RESULTS: Among 341 CRC patients, increased HDL-C appeared to have a beneficial impact on recurrence-free survival (RFS) for CRC patients, especially among statin users (hazard ratio [HR] for 0.1 mmol/L increase = 0.58; 95 % confidence interval [CI]: 0.43, 0.78). Increased LDL-C and TG were not associated with RFS. Increased lipids showed a near-null effect on CRC recurrence [e.g. HR (95 % CI) for 0.1 mmol/L increase LDL = 1.01 (0.97, 1.19)] among non-statin users. CONCLUSION: Serum lipid levels of LDL-C and TG do not appear to be associated with CRC recurrence. Further investigation of the role of HDL-C in CRC recurrence may be of interest based on the suggestive inverse association observed here.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Lipídeos/sangue , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
10.
Aliment Pharmacol Ther ; 52(1): 143-154, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32412143

RESUMO

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased risk of cancer. AIM: To assess the risk of pancreatic cancer in IBD compared to the general population. METHODS: Patients with incident IBD 1969-2017 were identified in Danish and Swedish National Patient Registers and through biopsy data, and were matched to IBD-free reference individuals by sex, age, place of residence and year of IBD diagnosis. We linked data to Cancer and Causes of Death Registers and examined the absolute and relative risks of pancreatic cancer and pancreatic cancer death. RESULTS: Among 161 926 patients followed for 2 000 951 person years, 442 (0.27%) were diagnosed with pancreatic cancer compared to 3386 (0.21%) of the 1 599 024 reference individuals. The 20-year cumulative incidence was 0.34% (95% confidence interval 0.30-0.38) vs 0.29% (0.28-0.30). The incidence rate was 22.1 (20.1-24.2)/100 000 person years in the patients (excluding the first year of follow-up: 20.8 [18.8-23.0]), and 16.6 (16.0-17.2) in the reference individuals. The hazard ratio (HR) for pancreatic cancer was increased overall: 1.43 (1.30-1.58), in subtypes (Crohn's disease: 1.44 [1.18-1.74]; ulcerative colitis: 1.35 [1.19-1.53]; IBD unclassified: 1.99 [1.50-2.64]) and especially in IBD patients with primary sclerosing cholangitis: 7.55 (4.94-11.5). Patients and reference individuals with pancreatic cancer did not differ in cancer stage (P = 0.17) or pancreatic cancer mortality (HR 1.07 [0.95-1.21]). CONCLUSIONS: Patients with IBD had an excess risk of pancreatic cancer, in particular patients with primary sclerosing cholangitis. However, the cumulative incidence difference after 20 years was small: 0.05%, that is, one extra pancreatic cancer per 2000 IBD patients.


Assuntos
Doenças Inflamatórias Intestinais/epidemiologia , Neoplasias Pancreáticas/epidemiologia , Adolescente , Adulto , Estudos de Coortes , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
11.
Clin Epidemiol ; 12: 113-121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32099477

RESUMO

Background: Among men and women diagnosed with colorectal cancer (CRC), 20-50% will develop a cancer recurrence. Cancer recurrences are not routinely captured by most population-based registries; however, linkage across Danish registries allows for the development of predictive models to detect recurrence. Successful application of such models in population-based settings requires validation against a gold standard to ensure the accuracy of recurrence identification. Objective: We apply a recently developed validation study design for prospectively collected validation data to validate predicted CRC recurrences against gold standard diagnoses from medical records in an actively followed cohort of CRC patients in Denmark. Methods: We use a Bayesian monitoring framework, traditionally used in clinical trials, to iteratively update classification parameters (positive and negative predictive values, and sensitivity and specificity) in an adaptive validation substudy design. This design allows determination of the sample size necessary to estimate the corresponding parameters and to identify when validation efforts can cease based on predefined criteria for parameter values and levels of precision. Results: Among 355 men and women diagnosed with CRC in Denmark and actively followed semi-annually, there were 63 recurrences diagnosed by active follow-up and 70 recurrences identified by a predictive algorithm. The adaptive validation design met stopping criteria for the classification parameters after 120 patients had their recurrence information validated. This stopping point yielded parameter estimates for the classification parameters similar to those obtained when the entire cohort was validated, with 66% less patients needed for the validation study. Conclusion: In this proof of concept application of the adaptive validation study design for outcome misclassification, we demonstrated the ability of the method to accurately determine when sufficient validation data have been collected. This method serves as a novel validation substudy design for prospectively collected data with simultaneous implementation of a validation study.

12.
Lancet Gastroenterol Hepatol ; 5(5): 475-484, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32066530

RESUMO

BACKGROUND: Crohn's disease is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance strategies, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account. Such biases can be accounted for by assessing CRC incidence by tumour stage and CRC mortality by tumour stage. We aimed to assess rates of incident CRC and CRC mortality among patients with Crohn's disease compared with the general population. METHODS: For this nationwide register-based cohort study, we used International Classification of Disease codes in national patient registers and pathology reports to identify incident cases of Crohn's disease. In Denmark we searched for incident cases between January, 1977, and December, 2011, and in Sweden between January, 1969, and December, 2017. For each patient with Crohn's disease, we identified up to ten reference individuals in national population registers and matched them by sex, age, calendar year, and place of residence. Matched reference individuals had to be alive and free of inflammatory bowel disease at the start of follow-up of index patients with Crohn's disease, and stopped contributing to reference person-years if they were diagnosed with inflammatory bowel disease. Our main outcome was death from CRC (main or contributory cause of death) as captured in the cause-of-death registers. Our secondary outcome was incident CRC, as defined by the cancer registers. We used Cox regression to estimate hazard ratios (HRs) for incident CRC and CRC mortality, taking tumour stage into account. We used a series of Cox models to estimate cause-specific HRs of the different competing outcomes (CRC diagnosis, CRC death, and other causes of death) and adjusted for tumour stage at CRC diagnosis. FINDINGS: During the 1969-2017 study period, we identified 47 035 patients with incident Crohn's disease (13 056 in Denmark and 33 979 in Sweden) and 463 187 matched reference individuals. During follow-up, 296 (0·47 per 1000 person-years) CRC deaths occurred among individuals with Crohn's disease compared with 1968 (0·31 per 1000 person-years) in reference individuals, corresponding to an overall adjusted HR of 1·74 (1·54-1·96). 499 (0·82 per 1000 person-years) cases of incident CRC were diagnosed in patients with Crohn's disease compared with 4084 (0·64 per 1000 person-years) cases in reference individuals, corresponding to an overall adjusted HR of 1·40 (95% CI 1·27-1·53). Patients with Crohn's disease who were diagnosed with CRC were at increased risk of CRC mortality compared with reference individuals also diagnosed with CRC (HR 1·42 [1·16-1·75] when adjusted for tumour stage), and tumour stage at CRC diagnosis did not differ between groups (p=0·27). Patients with Crohn's disease who had follow-up of 8 years or longer or who were diagnosed with primary sclerosing cholangitis (PSC) and hence were potentially eligible for CRC surveillance had an increased overall risk of CRC death (HR 1·40 [1·16-1·68]) or CRC diagnosis (HR 1·12 [0·98-1·28]). However, in patients potentially eligible for CRC surveillance we only found significantly increased risks in patients diagnosed with Crohn's disease before the age of 40 years, patients with disease activity in the colon only, or patients with PSC. INTERPRETATION: Patients with Crohn's disease are at increased risk of CRC diagnosis and CRC death. Patients with Crohn's disease who have CRC have a higher mortality than patients without Crohn's disease who are also diagnosed with CRC. CRC surveillance should likely be focused on patients diagnosed with Crohn's disease before the age of 40 years, on patients with colon inflammation, and on those who have PSC. FUNDING: Swedish Medical Society, Karolinska Institutet, Regional Agreement on Medical Training and Clinical Research between Stockholm County Council and Karolinska Institutet (ALF), Forte Foundation, Swedish Cancer Foundation, and Independent Research Fund Denmark.


Assuntos
Neoplasias Colorretais/epidemiologia , Doença de Crohn/epidemiologia , Vigilância da População , Adolescente , Adulto , Fatores Etários , Estudos de Casos e Controles , Colangite Esclerosante/epidemiologia , Estudos de Coortes , Neoplasias Colorretais/mortalidade , Doença de Crohn/diagnóstico , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Suécia/epidemiologia , Adulto Jovem
13.
Lancet ; 395(10218): 123-131, 2020 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-31929014

RESUMO

BACKGROUND: Ulcerative colitis (UC) is a risk factor for colorectal cancer (CRC). However, available studies reflect older treatment and surveillance paradigms, and most have assessed risks for incident CRC without taking surveillance and lead-time bias into account, such as by assessing CRC incidence by tumour stage, or stage-adjusted mortality from CRC. We aimed to compare both overall and country-specific risks of CRC mortality and incident CRC among patients with UC. METHODS: In this population-based cohort study of 96 447 patients with UC in Denmark (n=32 919) and Sweden (n=63 528), patients were followed up for CRC incidence and CRC mortality between Jan 1, 1969, and Dec 31, 2017, and compared with matched reference individuals from the general population (n=949 207). Patients with UC were selected from national registers and included in the analysis if they had two or more records with a relevant International Classification of Disease in the patient register (in the country in question) or one such record plus a colorectal biopsy report with a morphology code suggestive of inflammatory bowel disease. For every patient with UC, we selected matched reference individuals from the total population registers of Denmark and Sweden, who were matched for sex, age, birth year, and place of residence. We used Cox regression to compute hazard ratios (HRs) for incident CRC, and for CRC mortality, taking tumour stage into account. FINDINGS: During follow-up, we observed 1336 incident CRCs in the UC cohort (1·29 per 1000 person-years) and 9544 incident CRCs in reference individuals (0·82 per 1000 person-years; HR 1·66, 95% CI 1·57-1·76). In the UC cohort, 639 patients died from CRC (0·55 per 1000 person-years), compared with 4451 reference individuals (0·38 per 1000 person-years; HR 1·59, 95% CI 1·46-1·72) during the same time period. The CRC stage distribution in people with UC was less advanced (p<0·0001) than in matched reference individuals, but taking tumour stage into account, patients with UC and CRC remained at increased risk of CRC death (HR 1·54, 95% CI 1·33-1·78). The excess risks declined over calendar periods: during the last 5 years of follow-up (2013-17, Sweden only), the HR for incident CRC in people with UC was 1·38 (95% CI 1·20-1·60, or one additional case per 1058 patients with UC per 5 years) and the HR for death from CRC was 1·25 (95% CI 1·03-1·51, or one additional case per 3041 patients with UC per 5 years). INTERPRETATION: Compared with those without UC, individuals with UC are at increased risk of developing CRC, are diagnosed with less advanced CRC, and are at increased risk of dying from CRC, although these excess risks have declined substantially over time. There still seems to be room for improvement in international surveillance guidelines. FUNDING: The Swedish Medical Society, Karolinska Institutet, Stockholm County Council, Swedish Research Council, Swedish Foundation for Strategic Research, Independent Research Fund Denmark, Forte Foundation, Swedish Cancer Foundation.


Assuntos
Colite Ulcerativa/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Adulto , Idoso , Estudos de Coortes , Colite Ulcerativa/complicações , Colite Ulcerativa/mortalidade , Neoplasias Colorretais/mortalidade , Dinamarca/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Sistema de Registros , Suécia/epidemiologia , Adulto Jovem
14.
J Crohns Colitis ; 14(5): 630-635, 2020 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31811282

RESUMO

BACKGROUND: Patients with inflammatory bowel disease are at increased risk of extracolonic cancers. Little is known regarding this risk following total colectomy [TC]. METHODS: Patients who underwent TC for inflammatory bowel disease in Denmark during 1977-2013 were identified from the Danish National Patient Registry. Incidence rates of extracolonic cancers were determined through record linkage to the Danish Cancer Registry and compared with expected incidence rates in the general population. Standardized incidence ratios [SIRs] were calculated as the observed vs expected cancer incidence. RESULTS: In total, 4430 patients (3441 with ulcerative colitis [UC]; 989 with Crohn's disease [CD]) were followed for 54,183 person-years after TC. Following their surgery, 372 patients were diagnosed with extracolonic cancer compared to 331 expected [SIR = 1.1 (95% confidence interval {CI}: 1.0-1.2)]. The risk of extracolonic cancer overall was increased among patients with CD and TC (SIR = 1.5 [95% CI: 1.2-1.8]), but not among patients with UC and TC (SIR = 1.0 [95% CI: 0.9-1.2]). Patients with UC and TC had a higher risk of intestinal extracolonic cancer (SIR = 2.0 [95% CI: 1.4-2.7]). Patients with CD and TC had a higher risk of smoking-related cancers (SIR = 1.9 [95% CI: 1.2-2.9]), intestinal extracolonic cancer (SIR = 3.1 [95% CI: 1.6-5.5]) and immune-mediated cancers (SIR = 1.5 [95% CI: 1.0-2.1]). CONCLUSION: Patients with CD and TC had a higher risk of extracolonic cancer overall compared to the general population, while patients with UC and TC did not. Site-specific cancer risk varied according to inflammatory bowel disease type.

15.
Scand J Gastroenterol ; 54(9): 1176-1181, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31498716

RESUMO

Objective: Cecal intubation rate (CIR) is known to be inversely associated with interval colorectal cancer (CRC) risk. Cecal intubation may be achieved by the use of force and sedation jeopardizing patient safety. The Performance Indicator of Colonic Intubation (PICI) is defined as the proportion of colonoscopies achieving cecal intubation with use of ≤2 mg midazolam and no-mild patient-experienced discomfort. We aimed (i) to measure the variation of PICI between colonoscopists and colonoscopy units; (ii) to assess the correlation between the individual components of PICI; and (iii) to evaluate the association between PICI and commonly used performance indicators. Materials and methods: For the period 1 July 2015 through 30 June 2017 of the prevalent round of the Danish FIT-based CRC screening program, we included colonoscopies performed at four units in the Central Denmark Region within 60 days after a positive FIT-test. The PICI variation was evaluated using rates and ranges. Correlations between individual PICI components were assessed using Pearson correlation coefficients. Polyp detection rate (PDR), Adenoma detection rate (ADR), Polyp retrieval rate (PRR) and Withdrawal time (WT) were assessed within PICI quartiles. Results: The overall PICI was 78.7% with substantial variation between colonoscopists (40.0-91.9%) and units (72.6-82.0%). CIR was significantly correlated with patient-experienced comfort (r = 0.49, n = 73, p < .0001) and we observed that colonoscopists with a PICI between 79.9% and 84.3%) had the highest ADR. Conclusion: We found a substantial variation in PICI between colonoscopists and between colonoscopy units, which may reflect potential for quality improvements.


Assuntos
Colonoscopia/estatística & dados numéricos , Colonoscopia/normas , Detecção Precoce de Câncer/métodos , Indicadores de Qualidade em Assistência à Saúde , Adenoma/diagnóstico por imagem , Fatores Etários , Idoso , Ceco , Competência Clínica , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/efeitos adversos , Neoplasias Colorretais/diagnóstico por imagem , Dinamarca , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Intubação Gastrointestinal , Masculino , Midazolam/administração & dosagem , Pessoa de Meia-Idade , Sangue Oculto , Dor Processual/etiologia , Melhoria de Qualidade , Fatores Sexuais
16.
Am J Ther ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31356342

RESUMO

BACKGROUND: Aspirin inhibits platelet function and may therefore accelerate early lower gastrointestinal bleeding (LGIB) from colorectal cancer (CRC) precursor polyps. The bleeding may increase endoscopic polyp detection. STUDY QUESTION: To estimate the prevalence of polyps and CRC comparing new users of low-dose aspirin with nonusers who all received a diagnosis of LGIB and to investigate the mortality among these patients. STUDY DESIGN: Using Danish nationwide health registries, we conducted a cohort study (2006-2013) of all new aspirin users who also received a diagnosis of LGIB (n = 40,578). Each new user was matched with 5 nonusers with LGIB by gender and age at the LGIB diagnosis date. MEASURES AND OUTCOMES: We computed the prevalence and prevalence ratios (PRs) of colorectal polyps and CRCs, and the mortality ratios within 6 months after the LGIB, comparing new users with nonusers. RESULTS: We identified 1038 new aspirin users and 5190 nonusers with LGIB. We observed 220 new users and 950 nonusers recorded with endoscopically detected polyps. New aspirin users had a higher prevalence of conventional {PR = 1.28 [95% confidence interval (CI): 1.06-1.55]} and serrated [PR = 1.31 (95% CI: 0.95-1.80)] polyps. New users and nonusers had a similar prevalence of CRC [PR = 1.04 (95% CI: 0.77-1.39)]. However, after stratifying by location of CRC, the prevalence of proximal tumors was lower [PR = 0.71 (95% CI: 0.35-1.43)] in new users than in nonusers. No difference in mortality was observed. CONCLUSIONS: These findings indicate that new use of low-dose aspirin is associated with an increased detection of colorectal polyps compared with nonuse.

17.
JBI Database System Rev Implement Rep ; 17(11): 2265-2300, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31188154

RESUMO

OBJECTIVE: The objective of this review was to assess the association between quality indicators used to evaluate individual colonoscopist performance and subsequent interval colorectal cancers (CRCs) in patients participating in bowel cancer screening programs. INTRODUCTION: Colorectal cancer is a leading cause of cancer death. Bowel cancer screening has been shown to reduce CRC mortality and morbidity, and has therefore been introduced in many countries. Endoscopy societies have developed quality assurance guidelines and guidelines on quality indicators for screening colonoscopies. These quality indicators need to be validated against a relevant outcome to assess their value. INCLUSION CRITERIA: We included studies on screening colonoscopies conducted on participants in a bowel cancer screening program, regardless of comorbidity. Studies on procedures performed on patients with known CRC, hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis were excluded. We also included studies evaluating the quality indicators of withdrawal time (WT), cecal intubation rate (CIR) and adenoma detection rate (ADR). The search did not reveal any studies evaluating the quality indicators polyp retrieval rate and incomplete adenoma resection/incomplete polyp resection. Only studies with interval CRC as an outcome were included (i.e. CRC diagnosed after a negative screening colonoscopy, but before the next recommended examination date). METHODS: Published studies were searched in: MEDLINE, Embase, Web of Science and CINAHL. Unpublished studies were searched in: OpenGrey and Grey Literature Report. The sources were searched from 1980 to2018. Data were extracted using the JBI critical appraisal checklist for analytical cross sectional studies. A meta-analysis was conducted based on three of the colonoscopist dependent quality indicators: WT, CIR and ADR. RESULTS: Seven prospective and retrospective cohort studies were included out of 2373 papers identified after duplicates were removed. The included studies were on bowel cancer screening programs with colonoscopy as the primary screening tool, resulting in the inclusion of a total of 616,390 screening colonoscopies performed by 1431 colonoscopists and 2319 subsequent interval CRCs. Six studies were assessed as high-quality studies, and one study was of low quality. The meta-analysis on WT revealed a 61% lower risk of interval CRC among the patients if the mean WT per colonoscopist was >6 minutes as compared to a mean WT of <6 minutes (RR: 0.39 [95% CI: 0.23 - 0.66]). The meta-analysis on CIR revealed a 31% lower risk of interval CRC among the patients if the CIR per colonoscopist was ≥90% as compared to a CIR of <85% (RR: 0.69 [95% CI: 0.56 - 0.83]). One of two meta-analyses on the individual colonoscopist ADR suggested that this should be 15-19%, as compared to an ADR <10% (RR: 0.77 [95% CI: 0.62 - 0.96]), in order to significantly reduce the risk of interval CRC. The other meta-analysis on ADR revealed a significant association between an individual colonoscopist ADR of ≥25% and a lower risk of interval CRC as compared to an ADR of <25% (RR: 0.51 [95% CI: 0.33 - 0.80]). The meta-analyses on WT and CIR showed no heterogeneity concerning the significant results (I = 0.0%). A high variability across studies due to heterogeneity concerning an ADR of ≥20% resulted in an I = 59.9%, and an I = 63.2% for an ADR of ≥25%. CONCLUSIONS: To minimize the risk of interval CRC, it may be recommended that WT and CIRs are monitored in bowel cancer screening programs, with an optimal individual colonoscopist mean withdrawal time of >6 minutes and a cecal intubation rate of ≥90%. In bowel cancer screening programs using colonoscopy as their primary screening tool, it may be recommended that the individual colonoscopist ADR be 15-19% or better ≥25% to minimize the risk of interval CRC.


Assuntos
Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer , Indicadores de Qualidade em Assistência à Saúde/normas , Ceco , Humanos , Intubação , Fatores de Tempo
18.
Scand J Gastroenterol ; 54(4): 471-477, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30978128

RESUMO

Objective: From the prevalent round of the Danish FIT-based colorectal cancer (CRC) screening program, we aimed (i) to evaluate the quality of recorded data and (ii) to characterize the colonoscopies by measuring variation in performance indicators between colonoscopists and assessing the ratio between adenoma detection rate (ADR) and polyp detection rate (PDR). Materials and methods: This study included screening colonoscopies performed in Central Denmark Region within 60 days of a positive FIT-result from 1 July 2015 through 30 June 2017. The participants were the colonoscopists, performing these procedures. The quality indicators cecal intubation rate (CIR), PDR, polyp retrieval rate (PRR), ADR and withdrawal time (WT) were evaluated. ADR/PDR ratios were calculated. Results: The concordance between the recorded data and the colonoscopy reports showed Kappa values in the range of 0.47-0.97. The overall CIR was 90.6% (range 73.7%-100%), PDR: 51.9% (range 18.4%-70.2%), PRR: 94.6% (range 69.6%-100%), ADR (conventional adenomas): 50.6% (range 18.4%-70.2%), ADRx (conventional adenomas, traditional serrated adenomas and sessile serrated lesions with dysplasia): 50.9% (range 18.4%-70.2%) and the mean WT was 11.3 min (range 4.5-24.9 min). The ADR/PDR ratio was 92.8% (95% CI: 92.0%-93.6%) and the ADRx/PDR ratio was 93.2% (95% CI: 92.4%-93.9%). Conclusion: Data quality was generally high. We found considerable variation in performance indicators between colonoscopists reflecting the potential for improvement. Further, our findings revealed that the PDR might be a good proxy for ADR in the context of the prevalent round of FIT-based CRC screening programs.


Assuntos
Adenoma/diagnóstico , Pólipos do Colo/diagnóstico , Colonoscopia/estatística & dados numéricos , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Idoso , Confiabilidade dos Dados , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indicadores de Qualidade em Assistência à Saúde
19.
Pharmacoepidemiol Drug Saf ; 28(5): 609-615, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30779395

RESUMO

PURPOSE: To validate prescription registry data as a measurement of adherence to statins through a direct method using assays for selected statins in serial blood samples collected from two prospective cohorts of Danish colorectal cancer patients. METHODS: We linked information on statin prescriptions from the Aarhus University Prescription Database with the cancer cohorts from Aalborg University Hospital. For statin-prescribed patients, we calculated a prescription window covering the anticipated duration of the prescription. For each statin-prescribed patient with at least one blood sample in a prescription window, we selected without replacement a never-statin-prescribed patient matched on sex, age, and calendar year of surgery. Each of the selected blood samples were analyzed using assays to detect statins. We calculated the positive and negative predictive value of the prescription registry reporting using the assay result as the gold standard. RESULTS: We identified 73 ever-statin-prescribed patients with a total of 253 blood samples and 74 blood samples among never-statin-prescribed patients. The positive predictive value for prescribed patients, with presence of statins in at least one blood sample as the gold standard, was 93% (95% CI, 86%-97%) and the negative predictive value was 93% (95% CI, 86%-97%). Stratified results did not reveal substantial differences in predictive values. Fifty-two (71%) of the statin-prescribed patients had statins in every blood sample, suggesting continuous adherence. CONCLUSION: This study showed a high adherence with treatment with statins among colorectal cancer patients.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Inibidores de Hidroximetilglutaril-CoA Redutases/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia , Dinamarca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle
20.
Clin Epidemiol ; 10: 1411-1415, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349389

RESUMO

Background: Randomized controlled trials have not provided clear evidence for the use of self-expanding metal stents (SEMS) for colonic cancer obstruction. Existing observational research mainly originates from highly specialized single-center settings with limited generalizability. The conduct of population-based nationwide studies is possible by using Danish medical databases. However, the quality of the coding of SEMS procedures in these databases is unclear. Methods: From March 1, 2010 through December 31, 2013, we compared the registration of SEMS procedures among obstructive colorectal cancer patients in the Danish National Patient Register (DNPR) and the Danish Colorectal Cancer Group (DCCG) database to the registration in a prospective SEMS database (the reference standard). Results: Ninety-three patients were included in the reference standard for the evaluation of DNPR data. In the DNPR, only two patients were incorrectly registered (positive predictive value [PPV]=98%, 95% CI: 92%-100%) whereas six patients were not captured by the DNPR (sensitivity =94%, 95% CI: 87%-98%). For the evaluation of the DCCG database, the reference standard included 54 patients. Only two patients in the DCCG database were incorrectly recorded (PPV =95%, 95% CI: 82%-99%), whereas 19 patients were not captured by the DCCG database (sensitivity =65%, 95% CI: 51%-77%). Conclusion: We found high PPV and sensitivity of SEMS coding in the DNPR, supporting the use of these data in future research. The PPV of SEMS data in the DCCG database was high, but the sensitivity was low, suggesting that data on SEMS treatment from this database should be used with caution.

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