Colonoscopy findings after increasing two-stool faecal immunochemical test (FIT) cut-off: Cross-sectional analysis of the SCREESCO randomized trial.

BACKGROUND: We determined the impact of an increased two-stool faecal immunochemical test (FIT) cut-off on colonoscopy positivity and relative sensitivity and specificity in the randomized controlled screening trial screening of Swedish colons conducted in Sweden. METHODS: We performed a cross-sectional analysis of participants in the FIT arm that performed FIT between March 2014 and 2020 within the study registered with ClinicalTrials.gov, NCT02078804, who had a faecal haemoglobin concentration of at least 10 µg/g in at least one of two stool samples and who underwent a colonoscopy (n = 3841). For each increase in cut-off, we computed the positive predictive value (PPV), numbers needed to scope (NNS), sensitivity and specificity for finding colorectal cancer (CRC) and advanced neoplasia (AN; advanced adenoma or CRC) relative to cut-off 10 µg/g. RESULTS: The PPV for AN increased from 23.0% (95% confidence intervals [CI]: 22.3%-23.6%) at cut-off 10 µg/g to 28.8% (95% CI: 27.8%-29.7%) and 33.1% (95% CI: 31.9%-34.4%) at cut-offs 20 and 40 µg/g, respectively, whereas the NNS to find a CRC correspondingly decreased from 41 to 27 and 19. The PPV for AN was higher in men than women at each cut-off, for example 31.5% (95% CI: 30.1%-32.8%) in men and 25.6% (95% CI: 24.3%-27.0%) in women at 20 µg/g. The relative sensitivity and relative specificity were similar in men and women at each cut-off. CONCLUSION: A low cut-off of around 20-40 µg/g allows detection and removal of many AN compared to 10 µg/g while reducing the number of colonoscopies in both men and women.

Associations between pregnancy-related factors and birth characteristics with risk of rare uterine cancer subtypes: a Nordic population-based case-control study.

PURPOSE: Uterine sarcomas are a rare group of uterine malignancies. Due to the low incidence and changes in uterine sarcoma classification, risk factors are not well characterized. Our objective was to evaluate risk factors for uterine sarcoma and compare risk factors between uterine sarcoma, malignant mixed Mullerian tumors (MMMTs), and type I endometrial carcinomas. METHODS: This nested case-control study utilized linked data from population-based medical birth and cancer registries in Denmark, Finland, Norway, and Sweden. Up to 10 controls were matched on country and birth year for each uterine cancer case. Using multivariable adjusted multinomial logistic regression, estimates of the associations between pregnancy-related factors and risk of uterine sarcoma, MMMTs, and type I endometrial carcinomas were determined. RESULTS: Having a very-low-birth-weight infant (< 1500 vs. 2500-3999 g: OR [95% CI] 2.83 [1.61-4.96]) was associated with an increased risk of uterine sarcoma. Whereas, having a more recent pregnancy was associated with reduced risks of MMMT (< 10 vs. ≥ 30 years: 0.66 [0.20-2.23]) and type 1 endometrial carcinomas (0.35 [0.30-0.41]) but not uterine sarcomas (1.33 [0.90-1.98], p-heterogeneity < 0.01). CONCLUSION: Our study provides evidence that risk factors for uterine sarcoma and MMMT, previously grouped with uterine sarcomas, vary substantially. Additionally, MMMT and type I endometrial carcinomas are more similar than uterine sarcoma in that pregnancy complications like gestational hypertension and preeclampsia were associated with reduced risks of both but not uterine sarcoma, suggesting different etiologies.

The role of endoscopist adenoma detection rate in in sex differences in colonoscopy findings: cross-sectional analysis of the SCREESCO randomized controlled trial.

BACKGROUND: Fewer adenomas are detected at colonoscopy in women compared to men and failure to detect adenomas and sessile serrated polyps is associated with an increased risk of post-colonoscopy colorectal cancer. The aim of this study was to investigate whether this was in part due to the greater difficulty of conducting colonoscopy in women, with the difference being more apparent in colonoscopies conducted by less skilled endoscopists. MATERIAL AND METHODS: Cross-sectional exploratory analysis of data on 16,551 individuals undergoing a primary colonoscopy (PCOL group) or colonoscopy after positive faecal immunochemical test (FIT group) within the randomized controlled trial SCREESCO. Endoscopist adenoma detection rate (ADR; low or high) was determined based on each endoscopist's colonoscopies performed in SCREESCO. In each study group, the relationship between the sex difference in colonoscopy outcome and endoscopist ADR was assessed using multiplicative interaction tests. RESULTS: Endoscopists performed equally many colonoscopies in men and women (median 52% men). There were no signs of effect modification of the risk ratio of any finding (men vs women) by endoscopist ADR in the PCOL group (p = 0.33) or the FIT group (p = 0.30). The proportion of incomplete index colonoscopies was lower in men than in women in both groups and there was no effect modification by endoscopist ADR in either the PCOL group (p = 0.41) or the FIT group (p = 0.96). CONCLUSIONS: This study provides no evidence that endoscopist skill measured by ADR underlies the sex difference in adenoma detection at colonoscopy. This study has trial number NCT02078804 and is registered with ClinicalTrials.gov.

Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study.

BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).

Does smoking cessation affect postoperative healing following oral surgery among smokers? - a systematic review.

BACKGROUND: It is well documented that smokers suffer increased risk of postoperative complications after medical surgery, for example delayed healing and increased risk of infection. It is also known that preoperative smoking cessation can reduce the risk of these complications. Because of this there are guidelines regarding preoperative smoking cessation in non-oral medical surgery. There are however no specific guidelines regarding oral surgical procedures, such as surgical extractions, dentoalveolar surgery, periodontal surgery, or dental implantation. Nevertheless, it is common that dentists and oral surgeons recommend smoking cessation pre to oral surgical procedures. The aim with this systematic review was to see if there are any evidence in the literature, supporting preoperative smoking cessation in oral surgical procedures. METHODS: A systematic search of the electronic databases PubMed, Scopus, Web of Science, and Cochrane was conducted to identify studies addressing the effect of preoperative smoking cessation in oral surgical procedures. Included publications were subjected to preidentified inclusion criterion. Six examiners performed the eligibility and quality assessment of relevant studies. Risk of bias was assessed using ROBINS-I and RoB 2. Certainty assessment was carried out using GRADE. RESULTS: The initial search resulted in 2255 records, and after removal of 148 duplicates, 16 articles met an acceptable level of relevance. These were read in full text, whereof 12 articles were excluded, due to different intervention, outcome, or study design than stated in the review protocol. One study remained with moderate risk of bias and three were excluded due to high risk of bias. CONCLUSION: This systematic review could not determine the effect of smoking cessation pre to oral surgical procedures, in smokers. This indicates lack of knowledge in the effects of smoking cessation. We also conclude a lack of knowledge in how to design smoking cessation in the most effective way.

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n = 7,425, 83% papillary). Cases were matched to controls (n = 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR = 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR = 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR = 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR = 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR = 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR = 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis: A Scandinavian Cohort Study.

BACKGROUND & AIMS: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD. METHODS: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation. RESULTS: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16-1.50) and UC (HR, 1.09; 95% CI, 1.00-1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02-0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs. CONCLUSIONS: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.

COVID-19 and comedications in atrial fibrillation-a case-control study in Stockholm.

To test the main hypothesis that anticoagulation reduces risk of hospitalization, intensive care unit (ICU) admission and death in COVID-19. Nested case-control study among patients with atrial fibrillation (AF) in Stockholm. COVID-19 cases were matched to five disease-free controls with same sex, born within ± 1 years. Source population was individuals in Stockholm with AF 1997-2020. Swedish regional and national registers are used. National registers cover hospitals and outpatient clinics, local registers cover primary care. Records were linked through the personal identity number assigned to each Swedish resident. Cases were individuals with COVID-19 (diagnosis, ICU admission, or death). The AF source population consisted of 179,381 individuals from which 7548 cases were identified together with 37,145 controls. The number of cases (controls) identified from hospitalization, ICU admission or death were 5916 (29,035), 160 (750) and 1472 (7,360). The proportion of women was 40% for hospitalization and death, but 20% and 30% for admission to ICU in wave one and two, respectively. Primary outcome was mortality, secondary outcome was hospitalization, tertiary outcome was ICU admission, all with COVID-19. Odds ratios (95% confidence interval) for antithrombotics were 0.79 (0.66-0.95) for the first wave and 0.80 (0.64-1.01) for the second wave. Use of anticoagulation among patients with arrythmias infected with COVID-19 is associated with lower risk of hospitalization and death. If further COVID-variants emerge, or other infections with prothrombotic properties, this emphasize need for physicians to ensure compliance among vulnerable patients.

Detection rates of colorectal neoplasia during colonoscopies and their associated factors in the SCREESCO study.

BACKGROUND AND AIM: Colonoscopy quality, including lesion detectability, is variable, and factors influencing lesion detection are not fully understood. This study investigated lesion detection rates during colonoscopies and the associated factors in the SCREEning of Swedish COlons (SCREESCO) study. METHODS: In this cross-sectional analysis of data from SCREESCO, a large-scale randomized controlled trial of colorectal cancer screening in the Swedish population aged 60 years, we assessed data of first-time colonoscopies performed in both colonoscopy and fecal immunochemical test (FIT) arms. RESULTS: This study included 16 552 individuals. The adenoma detection rate was 23.9% and 37.8% in colonoscopy and FIT arms, respectively. Regarding colonoscopy procedures, a withdrawal time ≥ 6 min was associated with higher detection rates of advanced adenomas (adjusted odds ratio [AOR] 2.474, 95% confidence interval [CI] 1.295-4.723), adenomas (2.181, 1.515-3.140), and proximal serrated lesions (pSLs) (1.713, 1.007-2.915). Antispasmodic use was associated with higher detection rates of these lesions and sessile serrated lesions (SSLs) (AOR, 95% CI: 1.523, 1.295-1.791; 1.361, 1.217-1.522; 1.450, 1.247-1.687; and 1.810, 1.512-2.167, respectively). Insertion time > 20 min was related to lower detection rates of adenomas, pSLs, and SSLs (AOR, 95% CI: 0.753, 0.639-0.887; 0.640, 0.495-0.828; and 0.704, 0.518-0.955, respectively). The relationship between a recent period and higher detection rates of pSLs and SSLs was also demonstrated. CONCLUSION: Lesion detectability in SCREESCO was mostly acceptable with room for improvement. In addition to sufficient withdrawal time, antispasmodic use and acquiring skills enabling short insertion time may improve lesion detection. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02078804.

Colorectal Cancer in Childhood-onset Inflammatory Bowel Disease: A Scandinavian Register-based Cohort Study, 1969-2017.

Through linkage of data from Danish and Swedish national registers we identified 6937 patients with childhood (<18 years)-onset Crohn disease (CD), 8514 patients with childhood-onset ulcerative colitis (UC) and up to 10 times as many matched (sex, age, residence) reference individuals 1969-2017. During follow-up to a median age of 27 (interquartile range = 21-39) years, 25 (0.36%) CD patients were diagnosed with colorectal cancer (CRC) versus 43 (0.06%) reference individuals, and 113 (1.33%) UC patients versus 45 (0.05%) reference individuals. The hazard ratio (HR) for CRC was 6.46 (95% CI = 3.95-10.6) in CD and 32.5 (95% CI = 23.0-45.9) in UC and increased with decreasing age at diagnosis. The HR for CRC was increased for all phenotypes, but with higher estimates for colonic CD [17.9 (95% CI = 7.43-43.3)] and UC with extensive/pancolitis [36.3 (95% CI = 22.8-57.8)]. The relative risk of CRC was increased for all phenotypes of childhood-onset inflammatory bowel disease. Age at onset may be considered an additional risk factor when implementing surveillance programs.

Tumour necrosis factor inhibitors in Crohn's disease and the effect on surgery rates.

AIM: Surgery is an important therapeutic option for Crohn's disease. The need for first bowel surgery seems to have decreased with the introduction of tumour necrosis factor inhibitors (TNFi; adalimumab or infliximab). However, the impact of TNFi on the need for intestinal surgery in Crohn's disease patients irrespective of prior bowel resection is not known. The aim of this work is to compare the incidence of bowel surgery in Crohn's disease patients who remain on TNFi treatment versus those who discontinue it. METHOD: We performed a nationwide register-based observational cohort study in Sweden of all incident and prevalent cases of Crohn's disease who started first-line TNFi treatment between 2006 and 2017. Patients were categorized according to TNFi treatment retention less than or beyond 1 year. The study cohort was evaluated with regard to incidence of bowel surgery from 12 months after the first ever TNFi dispensation. RESULTS: We identified 5003 Crohn's disease patients with TNFi exposure: 3748 surgery naïve and 1255 with bowel surgery prior to TNFi initiation. Of these patients, 7% (n = 353) were subjected to abdominal surgery during the first 12 months after the start of TNFi and were subsequently excluded from the main analysis. A majority (62%) continued TNFi for 12 months or more. Treatment with TNFi for less than 12 months was associated with a significantly higher surgery rate compared with patients who continued on TNFi for 12 months or more (hazard ratio 1.26, 95% CI 1.09-1.46; p = 0.002). CONCLUSION: Treatment with TNFi for less than 12 months was associated with a higher risk of bowel surgery in Crohn's disease patients compared with those who continued TNFi for 12 months or more.

Inflammatory bowel disease and risk of small bowel cancer: a binational population-based cohort study from Denmark and Sweden.

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.

Colorectal cancer in ulcerative colitis: a Scandinavian population-based cohort study.

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.

Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964-2014.

OBJECTIVES: To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. DESIGN: Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873. RESULTS: During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn's disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002-2014 had 2.3 years shorter mean estimated life span than matched comparators. CONCLUSIONS: Adult-onset and elderly-onset patients with UC, Crohn's disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.

Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients-A nationwide study.

Solid organ transplant recipients (OTRs) have an increased cancer risk but their survival once diagnosed with cancer has seldom been assessed. We therefore investigated cancer-specific survival among OTRs with a wide range of cancer forms nationally in Sweden. The study included 2,143 OTRs with cancer, and 946,089 nontransplanted cancer patients diagnosed 1992-2013. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression models adjusted for age, sex and calendar year. Median follow-up was 3.1 (range 0-22) years. Overall, OTRs diagnosed with any cancer had a 35% higher rate of cancer death compared to nontransplanted cancer patients (HR: 1.35, 95% CI: 1.24-1.47). Specifically, higher rates of cancer-specific death were observed among OTRs diagnosed with Hodgkin lymphoma (HR: 15.0, 95% CI: 5.56-40.6), high-grade non-Hodgkin lymphoma (HR: 2.68, 95% CI: 1.90-3.77), malignant melanoma (HR: 2.80, 95% CI: 1.74-4.52) and urothelial (HR: 2.56, 95% CI: 1.65-3.97), breast (HR: 2.12, 95% CI: 1.38-3.25), head/neck (HR: 1.55, 95% CI: 1.02-2.36) and colorectal (HR: 1.42, 95% CI: 1.07-1.88) cancer. The worse outcomes were not explained by differences in distribution of cancer stage or histologic subtypes. For other common cancer forms such as prostate, lung and kidney cancer, the prognosis was similar to that in nontransplanted cancer patients. In conclusion, several but not all types of posttransplantation cancer diagnoses are associated with worse outcomes than in the general population. Reasons for this should be further explored to optimize posttransplantation cancer management.

Associations of pregnancy-related factors and birth characteristics with risk of endometrial cancer: A Nordic population-based case-control study.

Many pregnancy-related factors are associated with reduced endometrial cancer risk. However, it remains unclear whether pregnancy-related complications (e.g., hypertensive conditions) are associated with risk and whether these associations vary by endometrial cancer subtype. Thus, we evaluated the risk of endometrial cancer, overall and by subtype, in relation to pregnancy-related factors, pregnancy complications and birth characteristics. Utilizing population-based register data from four Nordic countries, we conducted a nested case-control analysis of endometrial cancer risk. We included 10,924 endometrial cancer cases and up to 10 matched controls per case. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived from unconditional logistic regression models. We further evaluated associations by individual histology (i.e., endometrioid, serous, etc.) or, for rare exposures (e.g., pregnancy complications), by dualistic type (Type I [n = 10,343] and Type II [n = 581]). Preexisting and pregnancy-related hypertensive conditions were associated with increased endometrial cancer risk (OR [95% CI]: preexisting hypertension 1.88 [1.39-2.55]; gestational hypertension 1.47 [1.33-1.63]; preeclampsia 1.43 [1.30-1.58]), with consistent associations across dualistic type. Increasing number of pregnancies (≥4 vs. 1 birth: 0.64 [0.59-0.69]) and shorter time since last birth (<10 vs. ≥30 years: 0.34 [0.29-0.40]) were associated with reduced endometrial cancer risk, with consistent associations across most subtypes. Our findings support the role for both hormonal exposures and cell clearance as well as immunologic/inflammatory etiologies for endometrial cancer. This research supports studying endometrial hyperplasia, a precursor condition of endometrial cancer, in the context of pregnancy-related exposures, as this may provide insight into the mechanisms by which pregnancy affects subsequent cancer risk.

Pregnancy-related risk factors for sex cord-stromal tumours and germ cell tumours in parous women: a registry-based study.

BACKGROUND: Non-epithelial ovarian cancers are divided into sex cord-stromal tumours (SCSTs) and germ cell tumours (GCTs). Whereas parity and other pregnancy-related factors are protective for epithelial ovarian cancer, their associations with SCSTs and GCTs remains unclear. METHODS: Using data from the medical birth registries from Denmark, Finland, Norway and Sweden, we compared all parous women with a diagnosis of SCSTs (n = 420) or GCTs (n = 345) 1970-2013 with up to 10 parous controls (SCSTs n = 4041; GCTs n = 2942) matched on the cases' birth year and country. We used conditional logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) of associations between pregnancy-related factors and SCSTs and GCTs. RESULTS: The risk of SCSTs, but not GCTs, decreased with higher age at last birth [≥40 versus <25 years: OR 0.48 (95% CI 0.23-0.98)]. The risk of SCSTs (but not GCTs) also decreased with shorter time since last birth. Number of births, preterm birth, preeclampsia, and offspring size were not associated with risk of SCSTs or GCTs. CONCLUSIONS: We found a decreased risk of SCSTs with higher age at last birth and shorter time since last birth. The risk of SCSTs (but not GCTs) may be influenced by the woman's reproductive history.

Postcolonoscopy Colorectal Cancer in Sweden From 2003 to 2012: Survival, Tumor Characteristics, and Risk Factors.

BACKGROUND & AIMS: The rate of postcolonoscopy colorectal cancer (PCCRC) is a measure of colonoscopy quality, but there are conflicting results from studies of survival times of patients with PCCRC. We assessed survival times of patients with PCCRC and characterized the microscopic and macroscopic features of postcolonoscopy colorectal tumors. METHODS: We performed a population-based cohort study using data from a database in Sweden, on 458,937 colonoscopies (54.0% women) performed from 2003 through 2012. Rates of colorectal cancer within 3 years of a colonoscopy were calculated based on the World Endoscopy Organization guidelines. Risk factors were evaluated using Poisson regression analysis. We used Cox regression models and Kaplan-Meier analyses, stratified by sex, to assess conditional survival. Logistic regression models were used to evaluate features of postcolonoscopy colorectal tumors, including stage location (right, left, or rectum) differentiation grade (high or low), synchronous tumors, perineural growth, resection margins, and mucinous and vessel characteristics. RESULTS: Within 36 months after a colonoscopy, there were 19,184 individuals who had received a diagnosis of CRC; 1384 of these were PCCRCs (7.2%). The proportion of individuals with PCCRC decreased from 9.4% in 2003 to 6.1% in 2012. The largest risk factors for PCCRC were a prior diagnosis of CRC (relative risk [RR], 3.31; 95% CI, 2.71-4.04), ulcerative colitis (RR, 5.44; 95% CI, 4.75-6.23), Crohn's disease (RR, 3.81; 95% CI, 2.98-4.87), and prior polypectomy (RR, 2.32; 95% CI, 1.97-2.72). Individuals with PCCRCs had shorter survival times than individuals with CRCs detected during the index colonoscopy. Multivariate hazard ratios for PCCRC were 2.75 for men (95% CI, 2.21-3.42) and 2.00 for women (95% CI, 1.59-2.52), respectively. Individuals with left-side PCCRC had shorter survival times than patients with CRC detected during the index colonoscopy. Postcolonoscopy colorectal tumors had increased odds of low differentiation grade (odds ratio, 1.27; 95% CI, 1.09-1.49) compared with colorectal tumors detected during the index colonoscopy. CONCLUSIONS: In an analysis of colonoscopies in Sweden, the rate of PCCRCs decreased from 9.4% in 2003 to 6.1% in 2012. Diseases that require surveillance (such as prior colorectal neoplasms and inflammatory bowel diseases) are the largest risk factors for PCCRC. Patients with PCCRC have shorter survival times than patients with CRC detected during their initial colonoscopy-especially women and patients with left-side tumors.

Increased Mortality of Patients With Childhood-Onset Inflammatory Bowel Diseases, Compared With the General Population.

BACKGROUND & AIMS: Childhood-onset inflammatory bowel disease (IBD) is believed to be a more severe disease than adult-onset IBD, but there is little information on all-cause and cause-specific mortality in patients with childhood-onset IBD. We performed a population-based cohort study, with 50 years of follow-up, to estimate absolute and relative risks for overall and cause-specific mortality in patients with childhood-onset IBD, during childhood and adulthood. METHODS: We identified children with a diagnosis of IBD (younger than 18 years) in the Swedish nationwide health registers (1964-2014; n = 9442) and individuals from the general population matched for sex, age, calendar year, and place of residence (reference group; n = 93,180). Hazard ratios (HR) for death were estimated using Cox regression separately in patients with ulcerative colitis (n = 4671), Crohn's disease (n = 3780), and IBD unclassified (n = 991). HRs were compared among calendar periods. RESULTS: During 138,690 person-years of follow-up, 294 deaths (2.1/1000 person-years) occurred among the patients with IBD compared with 940 deaths in the reference group (0.7/1000 person-years; adjusted HR, 3.2; 95% confidence interval [CI] 2.8-3.7). Mean age at end of follow-up was 30 years. HRs were increased for patients with ulcerative colitis 4.0, 95% CI 3.4-4.7; Crohn's disease 2.3, 95% CI 1.8-3.0; and IBD unclassified 2.0, 95% CI 1.2-3.4. Among patients younger than 18 years, there were 27 deaths from IBD 4.9, 95% CI 3.0-7.7. Among young adults with IBD, we found no evidence that HRs for death decreased from 1964 through 2014 (P = .90). CONCLUSIONS: Children with IBD have a 3-fold increase in risk of death when followed through adulthood. The relative risk for death has not decreased with development of new drugs for treatment of IBD.

Beta-adrenergic receptor blockers and liver cancer mortality in a national cohort of hepatocellular carcinoma patients.

Background: ß-adrenergic signaling has been implicated in the pathology of hepatocellular carcinoma (HCC), but the evidence from clinical studies is limited. In this national population-based cohort study, we investigated the possible association of ß-adrenergic receptor blockers and cancer-specific mortality among patients with primary HCC diagnosed in Sweden between 2006 and 2014.Methods: Patients were identified from the Swedish Cancer Register (n = 2104) and followed until 31 December 2015. We used Cox regression to evaluate the association of ß-blockers dispensed within 90 days prior to cancer diagnosis, ascertained from the national Prescribed Drug Register, with liver cancer mortality identified from the Cause of Death Register, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and treatment procedures.Results: Over a median follow-up of 9.9 months, 1601 patients died (of whom 1309 from liver cancer). Compared with non-use, ß-blocker use at cancer diagnosis [n = 714 (predominantly prevalent use, 93%)] was associated with lower liver cancer mortality [0.82 (0.72-0.94); p = .005]. Statistically significant associations were observed for non-selective [0.71 (0.55-0.91); p = .006], ß1-receptor selective [0.86 [0.75-1.00); p = .049] and lipophilic [0.78 (0.67-0.90); p = .001] ß-blockers. No association was observed for hydrophilic ß-blockers [1.01 (0.80-1.28); p = .906] or other antihypertensive medications. Further analysis suggested that the observed lower liver cancer mortality rate was limited to patients with localized disease at diagnosis [0.82 (0.67-1.01); p = .062].Conclusion: ß-blocker use was associated with lower liver cancer mortality rate in this national cohort of patients with HCC. A higher-magnitude inverse association was observed in relation to non-selective ß-blocker use.