Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study.

Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation in the median age at diagnosis of common cancers worldwide, after adjusting for differences in population age structure. We used IARC's Cancer Incidence in Five Continents (CI5) Volume XI database, comprising cancer diagnoses between 2008 and 2012 from population-based cancer registries in 65 countries. We calculated crude median ages at diagnosis for lung, colon, breast and prostate cancers in each country, then adjusted for population age differences using indirect standardization. We showed that median ages at diagnosis changed by up to 10 years after standardization, typically increasing in low- and middle-income countries (LMICs) and decreasing in high-income countries (HICs), given relatively younger and older populations, respectively. After standardization, the range of ages at diagnosis was 12 years for lung cancer (median age 61-Bulgaria vs 73-Bahrain), 12 years for colon cancer (60-the Islamic Republic of Iran vs 72-Peru), 10 years for female breast cancer (49-Algeria, the Islamic Republic of Iran, Republic of Korea vs 59-USA and others) and 10 years for prostate cancer (65-USA, Lithuania vs 75-Philippines). Compared to HICs, populations in LMICs were diagnosed with colon cancer at younger ages but with prostate cancer at older ages (both pLMICS-vs-HICs < 0.001). In countries with higher smoking prevalence, lung cancers were diagnosed at younger ages in both women and men (both pcorr < 0.001). Female breast cancer tended to be diagnosed at younger ages in East Asia, the Middle East and Africa. Our findings suggest that the differences in median ages at cancer diagnosis worldwide likely reflect population-level variation in risk factors and cancer control measures, including screening.

Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

Integrative multiomics analysis highlights immune-cell regulatory mechanisms and shared genetic architecture for 14 immune-associated diseases and cancer outcomes.

Developing functional insight into the causal molecular drivers of immunological disease is a critical challenge in genomic medicine. Here, we systematically apply Mendelian randomization (MR), genetic colocalization, immune-cell-type enrichment, and phenome-wide association methods to investigate the effects of genetically predicted gene expression on ten immune-associated diseases and four cancer outcomes. Using whole blood-derived estimates for regulatory variants from the eQTLGen consortium (n = 31,684), we constructed genetic risk scores for 10,104 genes. Applying the inverse-variance-weighted MR method transcriptome wide while accounting for linkage disequilibrium structure identified 664 unique genes with evidence of a genetically predicted effect on at least one disease outcome (p < 4.81 × 10-5). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci by using gene expression data derived from 18 types of immune cells. This highlighted many cell-type-dependent effects, such as PRKCQ expression and asthma risk (posterior probability = 0.998), which was T cell specific. Phenome-wide analyses on 311 complex traits and endpoints allowed us to explore shared genetic architecture and prioritize key drivers of disease risk, such as CASP10, which provided evidence of an effect on seven cancer-related outcomes. Our atlas of results can be used to characterize known and novel loci in immune-associated disease and cancer susceptibility, both in terms of elucidating cell-type-dependent effects as well as dissecting shared disease pathways and pervasive pleiotropy. As an exemplar, we have highlighted several key findings in this study, although similar evaluations can be conducted via our interactive web platform.

Histology-specific standardized incidence ratio improves the estimation of second primary lung cancer risk.

BACKGROUND: Lung cancer (LC) survivors are at increased risk for developing a second primary cancer (SPC) compared to the general population. While this risk is particularly high for smoking-related SPCs, the published standardized incidence ratio (SIR) for lung cancer after lung cancer is unexpectedly low in countries that follow international multiple primary (IARC/IACR MP) rules when compared to the USA, where distinct rules are employed. IARC/IACR rules rely on histology-dependent documentation of SPC with the same location as the first cancer and only classify an SPC when tumors present different histology. Thus, SIR might be underestimated in cancer registries using these rules. This study aims to assess whether using histology-specific reference rates for calculating SIR improves risk estimates for second primary lung cancer (SPLC) in LC survivors. METHODS: We (i) use the distribution of histologic subtypes of LC in population-based cancer registry data of 11 regional cancer registries from Germany to present evidence that the conventional SIR metric underestimates the actual risk for SPLC in LC survivors in registries that use IARC/IACR MP rules, (ii) present updated risk estimates for SPLC in Germany using a novel method to calculate histological subtype-specific SIRs, and (iii) validate this new method using US SEER (Surveillance, Epidemiology, and End Results Program) data, where different MP rules are applied. RESULTS: The adjusted relative risk for lung cancer survivors in Germany to develop an SPLC was 2.98 (95% CI 2.53-3.49) for females and 1.15 (95% CI 1.03-1.27) for males using the novel histology-specific SIR. When using IARC/IACR MP rules, the conventional SIR underestimates the actual risk for SPLC in LC survivors by approximately 30% for both sexes. CONCLUSIONS: Our proposed histology-specific method makes the SIR metric more robust against MP rules and, thus, more suitable for cross-country comparisons.

Preeclampsia, antihypertensive medication use in pregnancy and risk of childhood cancer in offspring.

PURPOSE: Preeclampsia is a serious pregnancy complication that presents a significant risk to both the mother and the fetus. Preeclampsia and medications associated with its treatment are potentially linked to increased childhood cancer risk. Therefore, we examined the association between preeclampsia, antihypertensive medications, and childhood cancer in offspring. METHODS: Cases (n = 6,420) and controls (n = 160,484) were obtained from Danish national registries. We performed conditional logistic regression analyses to estimate the association between preeclampsia and childhood cancer risk, and examined the effects of antihypertensive medication use in pregnancy in relation to childhood cancer risk in the offspring with adjustment for relevant covariates. RESULTS: We observed an increased risk of acute lymphoblastic leukemia (ALL) among those whose mothers had preeclampsia (OR = 1.36, 95% CI 1.03, 1.79), especially for severe preeclampsia (OR = 2.36, 95% CI 1.37, 4.08). We also estimated an increased cancer risk in children born to mothers who were prescribed diuretics during pregnancy [OR = 2.09, 95% confidence interval (CI) 1.39, 3.14]. Intake of other antihypertensive medications was not associated with childhood cancer (OR = 0.78, 95% CI 0.50, 1.23). Among women who did not take diuretics in pregnancy, preeclampsia was associated with neuroblastoma (OR = 2.22, 95% CI 1.08, 4.55). CONCLUSION: Our findings suggested an increased risk for certain types of cancer in the offspring of mothers with preeclampsia and an increased risk of cancer with diuretic intake during pregnancy.

Effects of hypertension and use of antihypertensive drugs in pregnancy on the risks of childhood cancers in Taiwan.

BACKGROUND: Childhood cancers are associated with high mortality and morbidity, and some maternal prescription drug use during pregnancy has been implicated in cancer risk. There are few studies on the effects of hypertension, preeclampsia, and the use of antihypertensives in pregnancy on children's cancer risks. OBJECTIVE: This population-based cohort study analyzed the relationship between hypertension, preeclampsia, and antihypertensives taken during pregnancy and the risks of childhood cancers in the offspring. METHODS: Data on all children born in Taiwan between 2004 and 2015 (N = 2,294,292) were obtained from the Maternal and Child Health Database. This registry was linked with the National Health Insurance Database and Cancer Registry to get the records of maternal use of diuretics or other antihypertensives in pregnancy and records of children with cancer diagnosed before 13 years. We used Cox proportional hazard modeling to estimate the influence of maternal health conditions and antihypertensive drug exposure on the risks of developing childhood cancers. RESULTS: Offspring of mothers with hypertension (chronic or gestational) had a higher risk of acute lymphocytic lymphoma [hazard ratio (HR) = 1.87, 95% Confidence Interval (CI) 1.32 - 2.65] and non-Hodgkin's lymphoma (HR = 1.96, 95% CI 1.34 - 2.86). We estimated only a weak increased cancer risk in children whose mothers used diuretics (HR = 1.16, 95% CI 0.77 - 1.74) or used antihypertensives other than diuretics (HR = 1.15, 95% CI 0.86 - 1.54) before birth. CONCLUSIONS: In this cohort study, children whose mothers had chronic and gestational hypertension had an increased risk of developing childhood cancer.

Post-mastectomy reirradiation for ipsilateral T3N0M0 breast tumor relapse: a population-based study.

INTRODUCTION: Post-mastectomy radiotherapy is commonly recommended for T3N0M0 breast cancer, particularly in the presence of adverse prognostic factors. However, for T3N0M0 ipsilateral recurrences following breast-conserving surgery and adjuvant radiotherapy, the situation is distinct. Recurrence alone signifies a negative prognostic factor. Moreover, tumor relapses within previously irradiated areas exhibit enhanced radioresistance, and reirradiation of the chest wall carries an escalated risk of radiation-induced toxicity. This study aimed to assess the impact of post-mastectomy reirradiation (PM-reRT) on patient outcomes in cases of ipsilateral T3N0M0 breast tumor recurrence, using data from the SEER database. MATERIALS AND METHODS: We identified all patients who underwent treatment for primary non-metastatic breast cancer with breast-conserving surgery followed by adjuvant radiotherapy in the SEER database; among them, those who later experienced a localized T3N0M0 breast tumor recurrence and underwent total mastectomy were included. The study's goal was to compare overall survival (OS) and cancer-specific survival (CSS) between patients who underwent only mastectomy versus those who had mastectomy followed by adjuvant PM-reRT for their ipsilateral T3N0M0 breast tumor relapse. RESULTS: From 2000 to 2020, the SEER database recorded 44 patients with an ipsilateral T3N0M0 breast tumor recurrence after initial conservative treatment, managed with total mastectomy. No statistically significant differences in OS or CSS were observed between patients undergoing mastectomy (MT) alone versus those receiving MT combined with PM-reRT (p = 0.68 and p = 0.86, respectively). Five-year OS rates for the MT and MT + PM-reRT cohorts were 49.5% [95% CI: 29.9-81.8] and 41.7% [10.0-100.0], respectively, while 5­year CSS rates were 51.6% [12.0-99.5] and 58.3% [15.2-100.0], respectively. CONCLUSION: For patients undergoing total mastectomy after an ipsilateral T3N0M0 breast tumor recurrence, subsequent to initial breast cancer treatment involving breast-conserving surgery and adjuvant radiotherapy, chest wall reirradiation does not enhance survival outcomes. As such, it should not be routinely performed.

Cancer mortality in children surviving congenital heart interventions: A study from the Pediatric Cardiac Care Consortium.

INTRODUCTION: Children with congenital heart defects (CHD) have shorter life expectancy than the general population. Previous studies also suggest that patients with CHD have higher risk of cancer. This study aims to describe cancer-related mortality among patients with a history of CHD interventions using the Pediatric Cardiac Care Consortium (PCCC), a large US cohort of such patients. METHODS: We performed a retrospective cohort study of individuals (<21 years) who underwent interventions for CHD in the PCCC from 1982 to 2003. Patients surviving their first intervention were linked to the National Death Index through 2020. Multivariable models assessed risk of cancer-related death, adjusting for age, sex, race, and ethnicity. Patients with/without genetic abnormalities (mostly Down syndrome [DS]) were considered separately, due to expected differential risk in cancer. RESULTS: Among the 57,601 eligible patients in this study, cancer was the underlying or contributing cause of death for 208; with 20% among those with DS. Significantly increased risk of cancer-related death was apparent among patients with DS compared to the non-genetic group (aHR: 3.63, 95% confidence interval [CI]: 2.52-5.24, p < .001). For the group with non-genetic abnormalities, the highest association with cancer-related death compared to those with mild CHD was found among those with more severe CHD (severe two-ventricle aHR: 1.82, 95% CI: 1.04-3.20, p = .036, single-ventricle aHR: 4.68, 95% CI: 2.77-7.91, p < .001). CONCLUSIONS: Patients with more severe forms of CHD are at increased risk for cancer-related death. Despite our findings, we are unable to distinguish whether having CHD raises the risk of cancer or reduces survival.

Exploring diagnostic events and first referrals in cancer patient pathways in primary care. A questionnaire survey.

BACKGROUND: Cancer diagnostic pathways in general practice are often nonlinear, and several events can delay timely diagnosis. OBJECTIVES: To explore cancer diagnostic processes in general practice, examining how patients' symptom presentations, sex, and age are associated with the occurrence of predefined potentially delaying events and the first referrals. METHOD: General practices in 3 Danish Regions were invited to participate in a questionnaire survey, addressing patient's symptom presentation, diagnostic process events, and first referral. The general practitioners (GPs) received a list of their incident cancer patients from the preceding 2 years. RESULTS: In total 187 general practices participated, including 5,908 patients with the cancer diagnostic pathways initiated in general practice. Presenting with nonspecific symptoms was associated with potentially delaying events, even when the patient also had specific symptoms. Almost half of the patients were referred to a cancer patient pathway (CPP) first, men more often than women, and 10% were referred for acute hospitalization. In 23% of the diagnostic processes, GPs initially treated or referred patients on suspicion of another disease rather than cancer and waited due to normal examinations in 1 out of 20 patients. Excluding sex-specific cancers, these 2 events were more prevalent in women. Men less often complied to the follow-up agreement. Younger patients were less often first referred to a CPP and together with older patients more often first acutely hospitalized. CONCLUSION: In cancer diagnostic processes in general practice, first referrals and the occurrence of potentially delaying events are associated with the patient's age, sex, and specificity of symptoms.

Assessing Physicians' Recommendations for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Testing Among Minority Populations in Greater Philadelphia and New York City.

Deaths from liver cancer are on the rise and disproportionately affect minority racial/ethnic groups. In this study, we examined associations between physicians' recommendations for hepatitis B virus (HBV) and hepatitis C virus (HCV) screening and sociodemographic and lifestyle factors among minority populations in the areas of Greater Philadelphia and New York City. Using Poisson regression with robust variance estimation, we evaluated potential associations for 576 Hispanic American (HA), African American (AA), and Asian Pacific American (APA) adults, using blood tests as an outcome measure, with adjustment for sociodemographic factors We found that APAs (34.2%) were most likely to have a physician recommend HBV and HCV screening tests (34.2% and 27.1%, respectively), while HAs were least likely to receive an HBV recommendation (15.0%) and AAs were least likely to receive an HCV recommendation (15.3%). HAs were significantly likely to have never received a blood test for either HBV or HCV (RR = 1.25, 95% CI: 1.05, 1.49). APAs were significantly more likely to receive a screening recommendation for HBV (RR = 1.10, 95%CI: 1.01, 1.20) and to have a blood test (RR = 1.57, 95% CI: 1.06, 2.33). Our findings show that, among HAs, AAs, and APAs, physician recommendations are strongly associated with patients undergoing blood tests for HBV and HCV and that minority populations should increasingly be recommended to screen for HBV and HCV, especially given their elevated risk.

Epidemiology and management of oral cavity squamous cell carcinoma in Ireland.

INTRODUCTION: The epidemiology and management of oral cavity cancer have changed considerably in recent decades. This study examines epidemiological and management trends in oral cavity squamous cell carcinoma (OCSCC). METHODS: A retrospective cohort study of data from the National Cancer Registry of Ireland between 1994 and 2014. RESULTS: A total of 2725 patients were identified. The most common subsites were the tongue (34 %, n = 1025), lip (19 %, n = 575), floor of mouth (FOM) (18 %, n = 550), and retromolar trigone (RMT) (6 %, n = 189). The incidence of OCSCC remained largely unchanged (3.14 cases/100000/year) during the study period. 5-year disease-specific survival (DSS) was 58.6 % overall, varying between subsites (lip 85 %, RMT 62.9 %, tongue 54.7 %, and FOM 47.3 %). DSS improved over the study period (p = 0.03), in particular for tongue primaries (p = 0.007). Primary surgery significantly improved DSS versus radiotherapy (HR 0.28, p < 0.0001). Survival of T4 disease managed surgically was superior to that of T1 disease managed with radiotherapy. In node positive patients, chemotherapy improved overall survival (HR 0.8 p = 0.038) but not DSS (HR 0.87 p = 0.215). CONCLUSION: Primary surgery remains the standard of care in the management of OCSCC. Prognosis has improved in line with an increase in the use of primary surgery in the same time frame, though the incidence remains unchanged.

Temporality of body mass index, blood tests, comorbidities and medication use as early markers for pancreatic ductal adenocarcinoma (PDAC): a nested case-control study.

OBJECTIVE: Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC risk . DESIGN: We performed a population-based nested case-control study of 28 137 PDAC cases and 261 219 matched-controls in England. We described the associations of biomarkers with risk of PDAC using fractional polynomials and 5-year time trends using joinpoint regression. Associations with comorbidities and medication use were evaluated using conditional logistic regression. RESULTS: Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while following a U-shaped relationship for BMI and haemoglobin. Five-year trends showed biphasic BMI decrease and HbA1c increase prior to PDAC; early-gradual changes 2-3 years prior, followed by late-rapid changes 1-2 years prior. Liver markers and blood counts (white blood cell, platelets) showed monophasic rapid-increase approximately 1 year prior. Recent diagnosis of pancreatic cyst, pancreatitis, type 2 diabetes and initiation of certain glucose-lowering and acid-regulating therapies were associated with highest risk of PDAC. CONCLUSION: Risk of PDAC increased with raised HbA1c, liver markers, white blood cell and platelets, while followed a U-shaped relationship for BMI and haemoglobin. BMI and HbA1c derange biphasically approximately 3 years prior while liver markers and blood counts (white blood cell, platelets) derange monophasically approximately 1 year prior to PDAC. Profiling these in combination with their temporality could inform earlier PDAC diagnosis.

Exclusive use of different types of tobacco products, exposure to secondhand tobacco smoke and risk of subtypes of head and neck cancer among Indian males.

Tobacco products are used in vary many forms in India. Although the risk of tobacco uses in developing head and neck cancer (HNC) is known, risk by exclusive use of different tobacco products on HNC and its subtypes is poorly understood. A case-control study was conducted at a tertiary cancer hospital, which receives cases from different geographical regions of India with use of different types of tobacco products. The study included 824 oral cavity (OC), 149 oropharynx (OPX) 104 hypopharyngeal (HPX) and 81 larynx (LX) cancer cases and 1206 visitor controls. Information on 11 different types of tobacco products and exposure to secondhand smoke was collected through structured questionnaires. Odds ratios (OR) and 95% confidence intervals (CI), for the association of various HNC subtypes with exclusive use of each tobacco product compared to nonusers of tobacco were estimated using logistic regression models, after adjusting for potential confounders. Exclusive use of any type of smokeless tobacco product was strongly associated with all subtypes of HNC. Gutka chewing (only) had highest risk (OR = 33.67; 95% CI = 19.8-57.0) while exclusive users of betel quid with tobacco (BQ + T), tobacco quid, Khaini, Mawa and Mishri users had a OR of 14.77, 24.20, 5.33, 2.96 and 3.32, respectively, for development of OC. Bidi smoking and secondhand smoke was independently associated with increased risk of HNC. Our study indicates that tobacco control policies should focus on product specific awareness messaging that switching between tobacco product types is not a safe alternative to complete cessation.

Second primary cancer among 217702 colorectal cancer survivors: An analysis of national German cancer registry data.

With improvements in survival after colorectal cancer (CRC), more survivors are at risk of developing a second cancer, particularly in younger populations where CRC incidence is increasing. We estimated the incidence of second primary cancer (SPC) in CRC survivors and its potential risk factors. We identified CRC cases diagnosed between 1990 and 2011 and SPCs until 2013 from nine German cancer registries. Standardized incidence ratios (SIR) and absolute excess risk (AER) per 10 000 person-years were calculated and were stratified by index site: colon cancer (CC) and rectal cancer (RC), age and sex. Cox regression assessed potential SPC risk factors, including primary tumor-related therapy considering death as a competing risk. We included 217 202 primary CRC cases. SPC occurred in 18 751 CRC survivors (8.6%; median age: 69 years). Risk of cancer was significantly higher in CRC survivors than in the general population (SIR males 1.14, 95% confidence interval [CI] 1.12-1.17, AER = 24.7; SIR females 1.20, 95% CI 1.17-1.23, AER = 22.8). Increased risks of SPCs were observed for the digestive system, urinary system and female and male reproductive organs. CRC incidence increased in younger persons (<50 years) and SPC incidence was 4-fold in this group (SIR males 4.51, 95% CI 4.04-5.01, AER = 64.2; SIR females 4.03, 95% CI 3.62-4.48, AER = 77.0). Primary tumor-related factors associated with SPC risk were right-sided cancer and smaller primary tumor size. Treatment and risk of SPC differed for CC (no effect) and RC (lower risk after chemotherapy). CRC survivors have excess risk of developing SPC, with particular characteristics that could guide targeted surveillance.

Ovarian removal and subsequent breast cancer prognosis: a nationwide cohort study.

PURPOSE: To evaluate whether previous ovarian removal concomitant with benign hysterectomy improves prognosis in a cohort of women with breast cancer. METHODS: In this nationwide register-based cohort study, risk of recurrence and mortality were examined in 4563 women with invasive breast cancer and previous bilateral salpingo-oophorectomy (BSO) concomitant with benign hysterectomy, during 1977-2018. Comparing with benign hysterectomy alone, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated by Cox-proportional hazards regression models. Analyses were stratified on age at hysterectomy as a proxy for menopausal status (< 45, 45-54 and ≥ 55 years); tumor characteristics, estrogen receptor (ER)-status, and use of hormone therapy (HT) were included in multivariable models. RESULTS: Compared with hysterectomy alone, premenopausal (< 45 years) BSO at benign hysterectomy was associated with an age and calendar period adjusted HR of 1.48 (95% CI 0.83-2.65) for breast cancer recurrence within 10 years of follow-up, a HR of 1.07 (95% CI 0.66-1.72) for overall mortality after breast cancer, and a HR of 0.59 (95% CI 0.26-1.32) for breast cancer-specific mortality. The corresponding HRs for postmenopausal (≥ 55 years) BSO at benign hysterectomy were 1.51 (95% CI 0.73-3.12) for recurrences, 1.34 (95% CI 0.74-2.44) for overall mortality, and 1.78 (95% CI 0.74-4.30) for breast cancer mortality. Adjusting for tumor characteristics, ER-status and HT did not alter the results. CONCLUSION: Results from this cohort study did not indicate an improvement in breast cancer prognosis when removing the ovaries at benign hysterectomy prior to the cancer diagnosis.

Retrospective Cohort Analysis of the Impact of Puberty on Plexiform Neurofibroma Growth in Patients with Neurofibromatosis Type 1.

OBJECTIVE: To assess the hypothesis that plexiform neurofibroma (PN) growth rates increase during puberty. STUDY DESIGN: PN growth rates before and during puberty were compared in a retrospective cohort of children with neurofibromatosis type 1 with puberty defined by Tanner staging. Of 33 potentially eligible patients, 25 had adequate quality magnetic resonance imaging for volumetric analysis and were included in ≥1 anchor cohort. Volumetric analysis was performed for all available imaging studies within the 4 years before and after puberty, and before and after 9- and 11-year-old anchor scans. Linear regression was performed to estimate the slope of change (PN growth rate); growth rates were compared with paired t test or Wilcoxon matched-pairs signed rank test. RESULTS: There were no significant difference in rates of PN growth in milliliters per month or milliliters per kilogram per month in the prepubertal vs pubertal periods (mean, 1.33 ± 1.67 vs 1.15 ± 1.38 [P = .139] and -0.003 ± 0.015 vs -0.002 ± 0.02 [P = .568]). Percent increases of PN volumes from baseline per month were significantly higher prepubertally (1.8% vs 0.84%; P = .041) and seemed to be related inversely to advancing age. CONCLUSIONS: Puberty and its associated hormonal changes do not seem to influence PN growth rate. These findings support those previously reported, but from a typical population of children with neurofibromatosis type 1 with puberty confirmed by Tanner staging.

The impact of changes in gadolinium-enhancement on disease progression in children with neurofibromatosis type 1-associated optic pathway glioma: a retrospective analysis.

PURPOSE: There has been limited investigation of imaging features associated with visual acuity (VA) decline and initiation of treatment for patients with neurofibromatosis type 1 (NF1) and optic pathway glioma (OPG). METHODS: To evaluate the association of increased gadolinium enhancement with decline in VA, initiation of chemotherapy, and tumor growth, we performed a retrospective cohort study of children diagnosed with NF1-OPG between January 2006 to June 2016. Two cohorts were defined: a new diagnosis and a longitudinal cohort. Outcomes were examined at 1 and 2 years from initial diagnosis, and 1 and 2 years from initial increase in enhancement in the longitudinal cohort. RESULTS: Eighty patients were eligible; all 80 contributed to the new diagnosis cohort and 73 to the longitudinal cohort. Fifty-six patients (70%) demonstrated enhancing NF1-OPG at diagnosis. 39% of patients in the new diagnosis cohort and 45% of those in the longitudinal cohort developed increased enhancement during the study period. There was no significant association between increases in enhancement and VA decline in the newly diagnosed or longitudinal cohorts, as well as with initiation of treatment in the longitudinal cohort. Although there was an association of enhancement increase with treatment in the new diagnosis cohort, this association was not maintained when stratified by concurrent change in tumor size. CONCLUSION: Increased gadolinium-enhancement independent of a concurrent increase in tumor size on MRI should not be used as a marker of NF1-OPG progression and does not appear to be associated with visual decline or initiation of chemotherapy.

Incidence of gastrointestinal malignancies increases in persons received eradication therapy for Helicobacter pylori: A cohort study.

BACKGROUND: Long-term Helicobacter pylori infection increases the risk of gastric malignancies. Since the symptoms for H. pylori gastritis, as well as for several malignancies, may be nonexisting or highly unspecific, even H. pylori-positive subjects with underlying malignancies may receive eradication therapy. The aim was to assess the incidence of gastrointestinal and various other malignancies in individuals after eradication therapy for H. pylori infection. MATERIALS AND METHODS: A cohort of 217,554 subjects (120,344 women and 97,210 men), who had purchased specific combinations of drugs for H. pylori eradication therapy in 1994-2004, was identified by the Finnish National Prescription Registry and followed for cancer incidence until the end of 2008 (1.89 million person-years at risk). RESULTS: A total of 22,398 malignancies were identified in the cohort. In both genders, for the first 6 months after drug prescription, the standardized incidence ratios (SIRs) were between 5 and 32 for gastric, colorectal, and pancreatic cancers, and 2 and 3 for several other malignancies. Although later on the SIRs of most malignancies fell rapidly, those of gastric noncardia and lung cancers remained elevated up to 5 years of follow-up. The only SIRs below unity were seen in men for gastric cancers (cardia 0.61, 95% CI: 0.37-0.95; intestinal noncardia 0.74, 95% CI: 0.56-0.97) during the post-therapy period covering years 5-15. CONCLUSION: Incidence levels significantly above the population rates were detected for many malignancies. Although eradication of H. pylori may have a long-lasting protective effect against gastric cancer, H. pylori therapy may postpone the detection of malignancies possibly underlying unspecific gastrointestinal symptoms. Therefore, it should be emphasized that the diagnostic work-up for malignancies should not be stopped in case of detection and treatment of H. pylori infection.

Risk of gastric carcinoma will be low in generations born at turn of the 20th and 21st centuries in Finland. Modelling NORDCAN data of the age group specific incidence rates of gastric cancer with PLS-regression and with attention to age ('age effect') and year of the birth ('cohort effect').

BACKGROUND AND METHODS: We examined in NORDCAN database how the annual age group-specific incidence rates (IR) of gastric cancer (GCA), and correspondingly the GCA risk, have declined in Finland during the twentieth century, and whether this decline corresponds to a decrease in the cohort-specific prevalence rate of Helicobacter pylori (Hp) gastritis that is considered an important precancerous risk condition for GCA. RESULTS: In modelling with partial least squares regression (PLSR), the logarithmically transformed IRs (ln(IR) of GCA were well explained with age and birth cohort as explanatory model variables. By considering the observed (actual) and the PLSR-modelled IRs, the IR of GCA (and the risk of GCA) has decreased gradually in Finland from 1900 onward, cohort by cohort. By prediction of the future with PLSR, the IRs of GCA will be markedly lower in all cohorts during the twenty-first century than in the twentieth century. By PLSR modelling, less than 10 GCA cases per 100,000 people are predicted to appear annually in cohorts (generations) born at the turn of the 20th and 21st centuries, even when these people will be 60-80 years old in the years 2060-2070. CONCLUSIONS: The IR of GCA and GCA risk progressively declined by cohort in Finland during the whole twentieth century. This decline corresponds in extent and time window to earlier observations in the decline of the prevalence rate of Hp gastritis in the same birth cohorts and supports the hypothesis of the role of Hp gastritis as an important risk condition of GCA.

CRCBaSe: a Swedish register-based resource for colorectal adenocarcinoma research.

OBJECTIVES: To facilitate high-quality register-based research on colorectal cancer (CRC) in Sweden by constructing a database consisting of CRC patients, matched comparators, and relatives. MATERIAL AND METHODS: Patients with adenocarcinoma in the colon and/or rectum were identified in the Swedish Colorectal Cancer Register, a nationwide quality-of-care register. For each patient, six comparators from the general population were matched on birth year, sex, year of CRC diagnosis, and county. Comparators were free from CRC at the time of matching, but could later become cases. For both patients and comparators, first-degree relatives (parents, siblings, and children) were identified. Information from nationwide population-based registers was retrieved and linked to each individual in the database using the personal identification number unique to all Swedish residents. RESULTS: A total of 76,831 CRC patients diagnosed between 1995 and 2016 were identified (51% colon, 49% rectal; before 2007 only rectal cancer patients were included). Among all patients, 37% were stage I-II, 22% stage III, and 22% stage IV. The median follow-up time was 11.9 years (inter-quartile range, IQR: 8.6-15.3). Together with comparators and relatives, the database contains 2,413,139 individuals with information on demographics, dates and causes of death, in- and outpatient healthcare records, cancer diagnoses, prescribed and dispensed drugs, childbirths (among women), and social security information (such as sick leave and early retirement). CONCLUSION: The Colorectal Cancer Database Sweden (CRCBaSe) is a large and unique register-based data research platform, which opens up for clinically important, large epidemiological studies with innovative design in the field of colorectal adenocarcinoma.