Validation of IgA nephropathy diagnosis in the Swedish Renal Registry.

AIM: The Swedish Renal Registry (SRR) is a unique national quality registry that monitors the clinical trajectory of patients with chronic kidney disease (CKD). We have validated the biopsy data registered in the SRR for IgA Nephropathy (IgAN) diagnosis. METHODS: In total 25% of all patients (n = 142), registered with IgAN in the SRR after having performed a kidney biopsy during 2015-2019, were randomly selected. We obtained original biopsy and medical records for 139 (98%) patients. We evaluated the IgAN diagnosis using a standardized template, calculated its positive predictive value (PPV) with 95% confidence interval (CI) and reported clinical features at the time of diagnosis. RESULTS: A histological and clinical diagnosis of IgAN was confirmed in 132 of the 139 patients, yielding a PPV of 95% (95% CI 90-98%). Median age was 46 years (range: 18-85) and the male:female ratio was 2.1:1. The median creatinine level was 123 µmol/L, with a corresponding estimated glomerular filtration rate (eGFR) level of 51 mL/min/1.73m2. Histological features of IgA deposits were seen in all patients, hypercellularity in 102/132 (77.2%), C3 deposits in 98/132 (72.4%) and C1q deposits in 27/132 (20.5%) of the cases. CONCLUSION: Validating data is not research per se, but continuous validation of medical registries is an important feature necessary to ensure reliable data and the foundation of good epidemiological data for future research. Our validation showed a high PPV (95%) for IgAN diagnosis registered in the SRR. Clinical characteristics were consistent with previous reports. The biopsy data in the SRR will be a valuable resource in future IgAN research.

Acute cystitis in men- a nationwide study from primary care: antibiotic prescriptions, risk factors, and complications.

BACKGROUND: Research on acute cystitis in men is scarce and treatment guidelines differ between countries. Improved antibiotic stewardship is needed. AIM: To analyse antibiotic prescriptions and outcomes of Norwegian men diagnosed with cystitis in primary care. DESIGN & SETTING: A nationwide retrospective study was undertaken in primary care in Norway. METHOD: We identified all episodes of acute cystitis in men diagnosed in Norwegian primary care during 2012-2019. Choice of antibiotic (from the Norwegian Prescription Database), treatment failure, re-prescription, and complications were stratified by age, calendar year, and risk factors. We used logistic regression to explore predefined risk factors (diabetes, prostate cancer, benign prostate hyperplasia [BPH], urinary retention, and any cancer) with complications (pyelonephritis, prostatitis, and hospitalisation) and re-prescriptions. Linear regression was used to explore time trends. RESULTS: In total, 108 994 individuals contributed 148 635 episodes. Narrow-spectrum antibiotics were first-choice treatment in 71.0% of the episodes (52.5% of all prescriptions were pivmecillinam). More than 75% of the episodes with narrow-spectrum versus 82.2% of broad-spectrum treatment did not lead to any re-prescription or complication. Complications occurred in 1.8% of all episodes (0.5% prostatitis, 0.7% pyelonephritis, and 0.7% hospitalisation). BPH was associated with increased risk of complications and re-prescription. Diabetes was associated with a lower risk of re-prescriptions. Prostate cancer and urinary retention were associated with a lower risk of both complications and re-prescriptions. CONCLUSION: Our results support narrow-spectrum antibiotics as first-line treatment. Risk factor analyses warrants further investigation.

Hospitalizations and severe complications following acute sinusitis in general practice: a registry-based cohort study.

OBJECTIVES: To investigate complication rates of acute sinusitis in general practice, and whether antibiotic prescribing had an impact on complication rate. METHODS: All adult patients diagnosed with sinusitis in Norwegian general practice between 1 July 2012 and 30 June 2019 were included. GP consultation data from the Norwegian Control and Payment for Health Reimbursements Database were linked with antibiotic prescriptions (Norwegian Prescription Database) and hospital admissions (Norwegian Patient Registry). Main outcomes were sinusitis-related hospitalizations and severe complications within 30 days. Logistic regression was used to estimate associations between antibiotic prescriptions, prespecified risk factors, individual GP prescribing quintile, and outcomes. RESULTS: A total of 711 069 episodes of acute sinusitis in 415 781 patients were identified. During the study period, both annual episode rate (from 30.2 to 21.2 per 1000 inhabitants) and antibiotic prescription rate (63.3% to 46.5%; P < 0.001) decreased. Yearly hospitalization rate was stable at 10.0 cases per 10 000 sinusitis episodes and the corresponding rate of severe complications was 3.2, with no yearly change (P = 0.765). Antibiotic prescribing was associated with increased risk of hospitalization [adjusted OR 1.8 (95% CI 1.5-2.1)] but not with severe complications. Individual GP prescribing quintile was not associated with any of the outcomes, whereas risk factors such as previous drug abuse, or head injury, skull surgery or malformations, and being immunocompromised were significantly associated with increased risk of both outcomes. CONCLUSIONS: Severe complications of acute sinusitis were rare and no protective effect of high prescribing practice among GPs was found. Recommendations to further reduce antibiotic prescribing are generally encouraged, except for high-risk groups.

Long-term Follow-up of 84 Patients With Giant Prolactinomas-A Swedish Nationwide Study.

PURPOSE: To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas. METHODS: Register-based study of patients with giant prolactinomas [serum prolactin (PRL) > 1000 µg/L, tumor diameter ≥40 mm] identified in the Swedish Pituitary Register 1991-2018. RESULTS: Eighty-four patients [mean age 47 (SD ±16) years, 89% men] were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253 000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received 1 or more additional therapies, including surgery (n = 19), radiotherapy (n = 6), other medical treatments (n = 4), and chemotherapy (n = 2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up [median 9 years (interquartile range (IQR) 4-15)], the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n = 79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (P < .001 and P = .012, respectively). CONCLUSION: DAs effectively reduced PRL and tumor size, but approximately 1 patient out of 4 needed multimodal treatment. Our results suggest that the response to DA after 1 year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.

Target trial emulation of aspirin after diagnosis of colorectal polyps.

BACKGOUND AND AIMS: Previous research on the potential chemoprotective effect of aspirin for colorectal cancer (CRC) shows conflicting results. We aimed to emulate a trial of aspirin intiation in individuals with incident polyps. METHODS: We identified individuals registered with their first colorectal polyp in the nationwide gastrointestinal ESPRESSO histopathology cohort in Sweden. Individuals aged 45-79 years diagnosed with colorectal polyps 2006-2016 in Sweden without CRC or contraindications for preventive aspirin (cerebrovascular disease, heart failure, aortic aneurysms, pulmonary emboli, myocardial infarction, gastric ulcer, dementia, liver cirrhosis, or any other metastatic cancer) registered until the month of first polyp detection were eligible. Using duplication and inverse probability weighting, we emulated a target trial of aspirin initiation within 2 years of initial polyp detection. The main outcome measures were incident CRC, CRC mortality and all-cause mortality registered until 2019. RESULTS: Of 31,633 individuals meeting our inclusion criteria, 1716 (5%) initiated aspirin within 2 years of colon polyp diagnosis. Median follow-up was 8.07 years. The 10-year cumulative incidence in initiators versus non-initiators was 6% versus 8% for CRC incidence, 1% versus 1% for CRC mortality and 21% versus 18% for all-cause mortality. The corresponding hazard ratios were 0.88 (95% confidence interval, 95%CI = 0.86-0.90), 0.90 (95%CI = 0.75-1.06) and 1.18 (95%CI = 1.12-1.24). CONCLUSION: Aspirin initiation in individuals with polyp removal was linked to 2% lower cumulative incidence of CRC after 10 years but did not alter CRC mortality. We also observed a 4% increased risk difference of all-cause mortality at 10 years after the initiation of aspirin.

Mortality in small bowel cancers and adenomas - A nationwide, population-based matched cohort study.

BACKGROUND: Small bowel adenocarcinoma (SBA), neuroendocrine tumors (NET) and gastrointestinal stromal tumors (GIST) are neoplastic lesions of the small bowel while small bowel adenomas are precursors of SBA. AIM: To examine mortality in patients diagnosed with SBA, small bowel adenomas, NET and GIST. METHODS: We performed a population-based matched cohort study encompassing all individuals with SBA (n = 2289), adenomas (n = 3700), NET (n = 1884) and GIST (n = 509) in the small bowel diagnosed at any of Sweden's 28 pathology departments between 2000 and 2016 (the "ESPRESSO study"). Each case was matched by sex, age, calendar year and county of residence to up to 5 comparators from the general population. Through Cox regression we estimated hazard ratios (HRs) and 95% confidence intervals (95%CIs) for death and cause-specific death adjusting for education. RESULTS: During follow-up until December 31, 2017, 1836 (80%) deaths occurred in SBA patients, 1615 (44%) in adenoma, 866 (46%) in NET and 162 (32%) in GIST patients. This corresponded to incidence rates of 295, 74, 80 and 62/1000 person-years respectively and adjusted HRs of 7.60 (95%CI=6.95-8.31), 2.21 (2.07-2.36), 2.74 (2.50-3.01) and 2.33 (1.90-2.87). Adjustment for education had a substantial impact on the HR for death in SBA but not for other neoplasias. The predominant cause of excess death was cancer in all groups. CONCLUSION: This study confirms earlier findings of increased death rates in patients with SBA and NET in a modern study population. We also demonstrate a more than 2-fold increased risk of death in both GIST and the SBA precursor adenoma.

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.

Appendectomy and Future Risk of Microscopic Colitis: A Population-Based Case-Control Study in Sweden.

BACKGROUND AND AIMS: Microscopic colitis (MC) is an inflammatory bowel disease and a common cause of chronic diarrhea. Appendectomy has been suggested to have immunomodulating effects in the colon, influencing the risk of gastrointestinal disease. The relationship between appendectomy and MC has only been sparsely studied. METHODS: This was a case-control study based on the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, consisting of histopathological examinations in Sweden, linked to national registers. Patients with MC were matched to population controls by age, sex, calendar year of biopsy, and county of residence. Data on antecedent appendectomy and comorbidities were retrieved from the Patient Register. Unconditional logistic regression models were conducted presenting odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for country of birth and matching factors. Further subanalyses were made based on MC subtypes (lymphocytic colitis and collagenous colitis), follow-up time postappendectomy and severity of appendicitis. RESULTS: The study included 14,520 cases of MC and 69,491 controls, among these 7.6% (n = 1103) and 5.1% (n = 3510), respectively, had a previous appendectomy ≥1 year prior to MC or matching date. Patients with a previous appendectomy had an increased risk of MC in total (OR, 1.50; 95% CI, 1.40-1.61) and per the collagenous colitis subtype (OR, 1.67; 95% CI, 1.48-1.88) or lymphocytic colitis subtype (OR, 1.42; 95% CI, 1.30-1.55). The risk remained elevated throughout follow-up, and the highest risk was observed in noncomplicated appendicitis. CONCLUSIONS: This nationwide case-control study found a modestly increased risk of developing MC following appendectomy.

Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death.

BACKGROUND: Although colonoscopy is widely used as a screening test to detect colorectal cancer, its effect on the risks of colorectal cancer and related death is unclear. METHODS: We performed a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group). The primary end points were the risks of colorectal cancer and related death, and the secondary end point was death from any cause. RESULTS: Follow-up data were available for 84,585 participants in Poland, Norway, and Sweden - 28,220 in the invited group, 11,843 of whom (42.0%) underwent screening, and 56,365 in the usual-care group. A total of 15 participants had major bleeding after polyp removal. No perforations or screening-related deaths occurred within 30 days after colonoscopy. During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group. In intention-to-screen analyses, the risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18% (risk ratio, 0.82; 95% confidence interval [CI], 0.70 to 0.93). The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16). The number needed to invite to undergo screening to prevent one case of colorectal cancer was 455 (95% CI, 270 to 1429). The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04). CONCLUSIONS: In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. (Funded by the Research Council of Norway and others; NordICC ClinicalTrials.gov number, NCT00883792.).

Emergency hospital admissions, prognosis, and population mortality in Norway during the first wave of the Covid-19 epidemic.

BACKGROUND: During the first wave of the Covid-19 epidemic, a national lockdown was established in Norway, and inhabitants were asked to contact healthcare only if absolutely necessary. We investigated hospital admissions and mortality due to non-Covid-19 disease during the lockdown compared to previous years. METHODS: We compared the number of emergency admissions and in-hospital fatality for diagnoses probably unaffected (acute myocardial infarction, acute abdominal conditions, cerebrovascular diseases) and affected by the lockdown (infections, injuries) in the South-Eastern Health Region of Norway during weeks 12-22, 2020, compared to the mean of the same period in the years 2017-2019. We also compared population mortality March-May 2020, to the mean of the same period in years 2017-2019. RESULTS: A total of 280,043 emergency admissions were observed; 20,911 admissions probably unaffected, and 30,905 admissions probably affected by the lockdown. Admissions due to diagnoses probably unaffected was reduced by 12% (95% confidence interval (CI) 9-15%), compared to 2017-2019. Admissions for diagnoses probably affected was reduced by 30% (95% CI 28-32%). There was a 34% reduction in in-hospital fatality due to acute myocardial infarction (95% CI 4-56%), 19% due to infections (95% CI 1-33%), and no change for the other diagnoses, compared to 2017-2019. The risk of in-hospital mortality to total mortality was lower for acute myocardial infarction (relative risk 0.85, 95% CI 0.73-0.99) and injuries (relative risk 0.83, 95% CI 0.70-0.98). CONCLUSIONS: Even though fewer patients were admitted to hospital, there was no increase in in-hospital fatality or population mortality, indicating that those who were most in need still received adequate care.

Gall Bladder Disease and the Risk of Small Bowel Cancer-Results from a Nationwide Swedish Cohort Study.

BACKGROUND AND AIMS: Small bowel cancer is a rare but rising malignancy. The etiology is poorly understood and there is a need for large-scale studies. Gallbladder disease (GBD), inducing localized inflammation, has been suggested to increase small bowel cancer risk. METHODS: We retrieved nationwide data from Sweden's 28 pathology departments on all adults (age 20-79) with pathology-confirmed GBD diagnosed in 1965-2017. In total 156,390 GBD patients were matched with up to 5 matched comparators from the general population and follow-up started one year after GBD diagnosis. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. RESULTS: During a median follow-up of 12 years, we identified 92 small bowel adenocarcinomas, 132 adenomas, and 81 carcinoid tumors in the GBD cohort. Corresponding incidence rates were 4.8, 6.9, and 4.2 per 100,000 person-years (PY), compared to 3.2, 3.2, and 1.8 in matched comparators. The adjusted HR was 1.42 (95% CI = 1.08-1.87) for small bowel adenocarcinoma, 1.79 (95% CI = 1.41-2.27) for adenoma, and 2.07 (95% CI = 1.52-2.81) for carcinoid. The excess cancer risk was most pronounced during the first year of follow-up for adenocarcinomas and during the first six years for adenomas while for carcinoids the HR peaked 10-15 years after start of follow-up. CONCLUSIONS: In this nationwide cohort study, GBD was associated with an increased risk of small bowel cancer. The excess risk of small bowel adenocarcinoma was mainly seen during the first years of follow-up while small bowel carcinoid risk peaked 11-16 years after GBD diagnosis.

Cancer Risk in 47,241 Individuals With Celiac Disease: A Nationwide Cohort Study.

BACKGROUND & AIMS: Celiac disease (CD) is associated with increased mortality, in part due to cancer. Most studies investigating this cancer risk involved patients diagnosed before widespread increases in CD diagnosis rates and access to gluten-free food. We performed a population-based study of the risk of cancer in CD. METHODS: We identified all patients in Sweden with CD as defined as duodenal/jejunal villus atrophy, using the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. Each patient was matched to ≤5 controls by age, sex, and county. We used stratified Cox proportional hazards model, following patients from diagnosis until first cancer, or by December 31, 2016. RESULTS: Among 47,241 patients with CD, 30,080 (64%) were diagnosed since 2000. After a median follow-up of 11.5 years, the incidence of cancer was 6.5 and 5.7 per 1000 person-years in CD patients and controls, respectively. The overall risk of cancer was increased (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.07-1.15), but it was only significantly elevated in the first year after CD diagnosis (HR, 2.47; 95% CI, 2.22-2.74) and not subsequently (HR, 1.01; 95% CI, 0.97-1.05), although the risks of hematologic, lymphoproliferative, hepatobiliary, and pancreatic cancers persisted. The overall risk was highest in those diagnosed with CD after age 60 years (HR, 1.22; 95% CI, 1.16-1.29) and was not increased in those diagnosed before age 40. The cancer risk was similar among those diagnosed with CD before or after the year 2000. CONCLUSIONS: There is an increased risk of cancer in CD even in recent years, but this risk increase is confined to those diagnosed with CD after age 40 and is primarily present within the first year of diagnosis.

Cancer risk in patients with immunoglobulin A nephropathy: a Swedish population-based cohort study.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis affecting all ages and both sexes, but there is a lack of studies on its association with cancer and whether it is a paramalignant condition. METHODS: In a Swedish population-based cohort study we compared the risk of cancer among 3882 biopsy-verified IgAN patients diagnosed during 1974-2011 with 19 341 reference individuals and followed them until 2015. Cox regression was used to estimate hazard ratios (HRs) for cancer in IgAN patients versus controls and conditional logistic regression assessed the risk of cancer before the IgAN was confirmed. RESULTS: During a median follow-up of 12.6 years, 488 (12.6%) patients with IgAN and 1783 (9.2%) matched reference individuals were diagnosed with cancer {HR 1.70 [95% confidence interval (CI), 1.52-1.89]}. The increased risk was only seen in IgAN patients developing end-stage renal disease (ESRD), with an HR of 4.01 (95% CI 3.33-4.82) for any cancer and HR of 2.22 (95% CI 1.79-2.75) when excluding non-melanoma skin cancer (NMSC). Non-ESRD IgAN patients did not have an increased overall cancer risk [HR 1.13 (95% CI 0.99-1.30)]. There was no increased risk of cancer preceding an IgAN diagnosis [odds ratio 1.10 (95% CI 0.92-1.32)]. CONCLUSIONS: We found no support for IgAN being a paramalignant condition. There was an increased risk of cancer in IgAN patients, but only for those with ESRD. Our results indicate ∼6 extra cancer cases per 100 IgAN patients with ESRD per 10 years, or >17 extra cases if including NMSC as well.

Risk of colorectal cancer in first degree relatives of patients with colorectal polyps: nationwide case-control study in Sweden.

OBJECTIVE: To assess the risk of colorectal cancer (CRC) in first degree relatives (parents and full siblings) of patients with precursor lesions (polyps) for CRC. DESIGN: Case-control study. SETTING: Linkage to the multi-generation register and gastrointestinal ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) histopathology cohort in Sweden. PARTICIPANTS: 68 060 patients with CRC and 333 753 matched controls. MAIN OUTCOME MEASURES: Multivariable adjusted odds ratios of CRC according to the number of first degree relatives with a colorectal polyp and the histology of polyps and age at diagnosis in first degree relatives. Subgroup analysis was also performed according to age at CRC diagnosis and evaluated the joint association of family history of colorectal polyps and family history of CRC. RESULTS: After adjusting for family history of CRC and other covariates, having a first degree relative with a colorectal polyp (8.4% (5742/68 060) in cases and 5.7% (18 860/333 753) in controls) was associated with a higher risk of CRC (odds ratio 1.40, 95% confidence interval 1.35 to 1.45). The odds ratios ranged from 1.23 for those with hyperplastic polyps to 1.44 for those with tubulovillous adenomas. To better put this risk in perspective, the age specific absolute risk of colon and rectal cancers was estimated according to family history of polyps based on the 2018 national CRC incidence in Sweden. For example, the absolute risk of colon cancer in individuals aged 60-64 years with and without a family history of colorectal polyp was, respectively, 94.3 and 67.9 per 100 000 for men and 89.1 and 64.1 per 100 000 for women. The association between family history of polyps and CRC risk was strengthened by the increasing number of first degree relatives with polyps (≥2 first degree relatives: 1.70, 1.52 to 1.90, P<0.001 for trend) and decreasing age at polyp diagnosis (<50 years: 1.77, 1.57 to 1.99, P<0.001 for trend). A particularly strong association was found for early onset CRC diagnosed before age 50 years (≥2 first degree relatives: 3.34, 2.05 to 5.43, P=0.002 for heterogeneity by age of CRC diagnosis). In the joint analysis, the odds ratio of CRC for individuals with two or more first degree relatives with polyps but no CRC was 1.79 (1.52 to 2.10), with one first degree relative with CRC but no polyps was 1.70 (1.65 to 1.76), and with two or more first degree relatives with both polyps and CRC was 5.00 (3.77 to 6.63) (P<0.001 for interaction). CONCLUSIONS: After adjusting for family history of CRC, the siblings and children of patients with colorectal polyps are still at higher risk of CRC, particularly early onset CRC. Early screening for CRC might be considered for first degree relatives of patients with polyps.

Long-Term Incidence and Mortality of Colorectal Cancer After Endoscopic Biopsy With Normal Mucosa: A Swedish-Matched Cohort Study.

INTRODUCTION: Endoscopic screening reduces colorectal cancer (CRC) incidence and mortality. Individuals with a negative result are recommended to undergo rescreening within a 10-year interval, but evidence supporting this advice is limited. METHODS: We performed a matched cohort study using prospectively collected data from 88,798 individuals in Sweden with normal mucosa at the first colorectal biopsy (aged ≥50 years) in the nationwide gastrointestinal epidemiology strengthened by histopathology reports (ESPRESSO) (1965-2016) and 424,150 matched reference individuals from the general population. Cox proportional hazards regression estimated multivariable hazard ratios and 95% confidence intervals (CIs) of CRC incidence and mortality of incident CRCs up to 44 years of follow-up. RESULTS: In the normal biopsy and reference groups, respectively, the 20-year incidences of CRC were 3.03% and 4.53% and the 20-year mortalities of incident CRC were 0.89% and 1.54%. The multivariable hazard ratio comparing the normal biopsy and reference groups was 0.62 for CRC incidence (95% CI = 0.58-0.66, P < 0.001) and 0.56 for mortality of incident CRC (95% CI = 0.49-0.64, P < 0.001). When assessed by time interval after biopsy, lower CRC incidence and mortality were observed throughout the follow-up. The association seemed weaker for proximal colon cancer than for rectal and distal colon cancer. DISCUSSION: A normal colorectal biopsy was associated with lower CRC incidence and mortality for at least 20 years after the examination. Our findings confirm previous data and suggest that the screening intervals after a normal colonoscopy could be longer than the commonly recommended 10 years. It may be time to open the discussion for a revision of the international guidelines.

Psychiatric Disorders in Patients With a Diagnosis of Celiac Disease During Childhood From 1973 to 2016.

BACKGROUND & AIMS: Few studies have explored the link between childhood celiac disease and long-term psychiatric comorbidities. We performed a population-based cohort study of associations between childhood celiac disease and psychiatric disorders and investigated whether risk persists into adulthood. METHODS: We performed a nationwide study in Sweden using data from the Epidemiology Strengthened by histoPathology Reports in Sweden cohort. In this cohort, 19,186 children with a diagnosis of biopsy-verified celiac disease from 1973 through 2016 were identified from Sweden's 28 pathology departments. Each patient was matched with as many as 5 reference children (controls, n = 94,249). Data on psychiatric disorders were obtained from the patient register. We used Cox proportional modeling to estimate hazard ratios (HRs). RESULTS: During a median follow-up period of 12.3 years, 3174 children (16.5%) with celiac disease received a new diagnosis of a psychiatric disorder, compared with 13,286 controls (14.1%). Corresponding incidence rates were 12.2 per 1000 person-years (95% CI, 11.8-12.7) vs 10.3 per 1000 person-years (95% Cl, 10.2-10.5). Childhood celiac disease was associated with a 19% increase in risk of any psychiatric disorder (95% CI, 1.14-1.23); the increase in risk was observed in all childhood age groups. The highest HRs were seen in the first year after celiac diagnosis (HR, 1.70; 95% CI, 1.41-2.05). The risk increase persisted into adulthood (age, >18 y: HR, 1.11; 95% CI, 1.04-1.17). We found increased risks of mood disorders (HR, 1.20; 95% CI, 1.12-1.28), anxiety disorders (HR, 1.12; 95% CI, 1.06-1.19), eating disorders (HR, 1.34; 95% CI, 1.18-1.51), attention deficit hyperactivity disorder (HR, 1.29; 95% CI, 1.20-1.39), and autism spectrum disorder (HR, 1.47; 95% CI, 1.32-1.64). We found no statistically significant risk increase for psychotic disorders, psychoactive substance misuse, behavioral disorders, personality disorders, suicide attempt, or suicide. Celiac disease also was linked to an increased use of psychiatric drugs (HR, 1.34; 95% CI, 1.24-1.43). A conditional logistic regression found that psychiatric disorders also were more common before a diagnosis of celiac disease (odds ratio, 1.56; 95% CI, 1.39-1.76). CONCLUSIONS: Childhood celiac disease is associated with an increased risk of subsequent psychiatric disorders, which persists into adulthood. Mental health surveillance should be integral in the care of celiac disease.

Antibiotic Use Associated With Risk of Colorectal Polyps in a Nationwide Study.

BACKGROUND & AIMS: Use of antibiotics affects the composition of the microbiome and might affect development of colorectal polyps, which are precursors to colorectal cancer. METHODS: We performed a nested case-control study in Sweden of 45,744 patients with a colorectal polyp (cases) in the nationwide gastrointestinal ESPRESSO histopathology cohort, using unaffected full siblings as controls (n = 93,307). Polyps were classified by morphology SnoMed codes into conventional adenomas and serrated polyps. Through linkage to the Prescribed Drug Register, we assessed use and cumulative dispensations of antibiotic until 1 year prior to polyp diagnosis for cases and their sibling controls. RESULTS: During a median study period of 6.9 years, compared with non-users, users of antibiotics (including 28,884 cases [63.1%] and 53,222 sibling controls [57.0%]) had a higher risk of colorectal polyps (odds ratio [OR], 1.08; 95% CI, 1.04-1.13). Risk increased with higher number of dispensations (OR for ≥ 6 dispensations, 1.33; 95% CI, 1.25-1.43) (Ptrend < .0001). We observed a stronger association with polyps for broad-spectrum antibiotics (OR comparing users to non-users, 1.23; 95% CI, 1.18-1.29) than for narrow-spectrum antibiotics (OR, 1.05; 95% CI, 1.01-1.10), and for tetracyclines and quinolones (OR, 1.21) than penicillin and other classes (ORs ranged from 1.04 to 1.16). The findings remained robust with several sensitivity analyses, including use of a 2-year lead-in period for antibiotic assessment and correction for misclassification in controls. Use of broad-spectrum antibiotics was more strongly associated with risk of serrated polyps (OR, 1.29; 95% CI, 1.21-1.38) compared with risk of conventional adenomas (OR, 1.17; 95% CI, 1.11-1.24). We found no differences in risk of colon vs rectal polyps with antibiotic use (Pheterogeneity > .10). We found stronger associations for younger (<50 years) vs older adults (≥50 years) for users of quinolones, sulfonamides, trimethoprim, and cephalosporins (Pinteraction < .001). CONCLUSIONS: In a nationwide case-control study in Sweden, after accounting for hereditary and early life environmental factors, antibiotic use was associated with increased risk of colorectal polyps. Our findings indicate a role for intestinal dysbiosis in early stages of colorectal carcinogenesis.

Inflammatory Bowel Disease Is More Common in Patients with IgA Nephropathy and Predicts Progression of ESKD: A Swedish Population-Based Cohort Study.

BACKGROUND: Case reports suggest an association between inflammatory bowel disease, a chronic autoimmune condition linked to increased circulating IgA levels, and IgA nephropathy, the most common form of primary GN and a leading cause of ESKD. METHODS: In a Swedish population-based cohort study, we compared 3963 biopsy-verified IgA nephropathy patients with 19,978 matched controls between 1974 and 2011, following up participants until 2015. Inflammatory bowel disease data and ESKD status were obtained through national medical registers. We applied Cox regression to estimate hazard ratios (HRs) for future inflammatory bowel disease in IgA nephropathy and conditional logistic regression to assess risk of earlier inflammatory bowel disease in IgA nephropathy. We also explored whether inflammatory bowel disease affects development of ESKD in IgA nephropathy. RESULTS: During a median follow-up of 12.6 years, 196 (4.95%) patients with IgA nephropathy and 330 (1.65%) matched controls developed inflammatory bowel disease (adjusted HR, 3.29; 95% confidence interval [95% CI], 2.73 to 3.96). Inflammatory bowel disease also was more common before a confirmed IgA nephropathy diagnosis. Some 103 (2.53%) IgA nephropathy patients had an earlier inflammatory bowel disease diagnosis compared with 220 (1.09%) controls (odds ratio [OR], 2.37; 95% CI, 1.87 to 3.01). Both logistic regression (OR, 2.60; 95% CI, 2.02 to 3.35) and time-varying Cox regression (HR, 1.84; 95% CI, 1.33 to 2.55) demonstrated that inflammatory bowel disease was associated with increased ESKD risk in patients with IgA nephropathy. CONCLUSIONS: Patients with IgA nephropathy have an increased risk of inflammatory bowel disease both before and after their nephropathy diagnosis. In addition, among patients with IgA nephropathy, comorbid inflammatory bowel disease elevates the risk of progression to ESKD.

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease.

BACKGROUND & AIMS: The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts. METHODS: Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. RESULTS: During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance. CONCLUSIONS: In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease.

Risk of colorectal cancer incidence and mortality after polypectomy: a Swedish record-linkage study.

BACKGROUND: Long-term colorectal cancer incidence and mortality after colorectal polyp removal remains unclear. We aimed to assess colorectal cancer incidence and mortality in individuals with removal of different histological subtypes of polyps relative to the general population. METHODS: We did a matched cohort study through prospective record linkage in Sweden in patients aged at least 18 years with a first diagnosis of colorectal polyps in the nationwide gastrointestinal ESPRESSO histopathology cohort (1993-2016). For each polyp case, we identified up to five matched reference individuals from the Total Population Register on the basis of birth year, age, sex, calendar year of biopsy, and county of residence. We excluded patients and reference individuals with a diagnosis of colorectal cancer either before or within the first 6 months after diagnosis of the index polyp. Polyps were classified by morphology codes into hyperplastic polyps, sessile serrated polyps, tubular adenomas, tubulovillous adenomas, and villous adenomas. Colorectal cancer cases were identified from the Swedish Cancer Registry, and cause-of-death data were retrieved from the Cause of Death Register. We collected information about the use of endoscopic examination before and after the index biopsy from the Swedish National Patient Registry, and counted the number of endoscopies done before and after the index biopsies. We calculated cumulative risk of colorectal cancer incidence and mortality at 3, 5, 10, and 15 years, and computed hazard ratios (HRs) and 95% CIs for colorectal cancer incidence and mortality using a stratified Cox proportional hazards model within each of the matched pairs. FINDINGS: 178 377 patients with colorectal polyps and 864 831 matched reference individuals from the general population were included in our study. The mean age of patients at polyp diagnosis was 58·6 (SD 13·9) years for hyperplastic polyps, 59·7 (14·2) years for sessile serrated polyps, 63·9 (12·9) years for tubular adenomas, 67·1 (12·1) years for tubulovillous adenomas, and 68·9 (11·8) years for villous adenomas. During a median of 6·6 years (IQR 3·0-11·6) of follow-up, we documented 4278 incident colorectal cancers and 1269 colorectal cancer-related deaths in patients with a polyp, and 14 350 incident colorectal cancers and 5242 colorectal cancer deaths in general reference individuals. The 10-year cumulative incidence of colorectal cancer was 1·6% (95% CI 1·5-1·7) for hyperplastic polyps, 2·5% (1·9-3·3) for sessile serrated polyps, 2·7% (2·5-2·9) for tubular adenomas, 5·1% (4·8-5·4) for tubulovillous adenomas, and 8·6% (7·4-10·1) for villous adenomas compared with 2·1% (2·0-2·1) in reference individuals. Compared with reference individuals, patients with any polyps had an increased risk of colorectal cancer, with multivariable HR of 1·11 (95% CI 1·02-1·22) for hyperplastic polyps, 1·77 (1·34-2·34) for sessile serrated polyps, 1·41 (1·30-1·52) for tubular adenomas, 2·56 (2·36-2·78) for tubulovillous adenomas, and 3·82 (3·07-4·76) for villous adenomas (p<0·05 for all polyp subtypes). There was a higher proportion of incident proximal colon cancer in patients with serrated (hyperplastic and sessile) polyps (52-57%) than in those with conventional (tubular, tubulovillous, and villous) adenomas (30-46%). For colorectal cancer mortality, a positive association was found for sessile serrated polyps (HR 1·74, 95% CI 1·08-2·79), tubulovillous adenomas (1·95, 1·69-2·24), and villous adenomas (3·45, 2·40-4·95), but not for hyperplastic polyps (0·90, 0·76-1·06) or tubular adenomas (0·97, 0·84-1·12). INTERPRETATION: In a largely screening-naive population, compared with individuals from the general population, patients with any polyps had a higher colorectal cancer incidence, and those with sessile serrated polyps, tubulovillous adenomas, and villous adenomas had a higher colorectal cancer mortality. FUNDING: US National Institutes of Health, American Cancer Society, American Gastroenterological Association, Union for International Cancer Control.