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.

Changes in tuberculosis risk after transplantation in the setting of decreased community tuberculosis incidence: a national population-based study, 2008-2020.

BACKGROUND: Transplant recipients are immunocompromised and vulnerable to developing tuberculosis. However, active tuberculosis incidence is rapidly declining in South Korea, but the trend of tuberculosis infection among transplant recipients has not been elucidated. This study aimed to evaluate the risk of active tuberculosis after transplantation, including risk factors for tuberculosis and standardized incidence ratios, compared with that in the general population. METHODS: This retrospective study was conducted based on the South Korean health insurance review and assessment database among those who underwent transplantation (62,484 recipients) between 2008 and 2020. Tuberculosis incidence was compared in recipients treated during higher- (2010-2012) and lower-disease burden (2016-2018) periods. Standardized incidence ratios were analyzed using the Korean Tuberculosis Surveillance System. The primary outcome was the number of new tuberculosis cases after transplantation. RESULTS: Of 57,103 recipients analyzed, the overall cumulative incidence rate 1 year after transplantation was 0.8% (95% confidence interval [CI]: 0.7-0.8), significantly higher in the higher-burden period than in the lower-burden period (1.7% vs. 1.0% 3 years after transplantation, P < 0.001). Individuals who underwent allogeneic hematopoietic stem cell transplantation had the highest tuberculosis incidence, followed by those who underwent solid organ transplantation and autologous hematopoietic stem cell transplantation (P < 0.001). The overall standardized incidence ratio was 3.9 (95% CI 3.7-4.2) and was the highest in children aged 0-19 years, at 9.0 (95% CI 5.7-13.5). Male sex, older age, tuberculosis history, liver transplantation, and allogeneic hematopoietic stem cell transplantation were risk factors for tuberculosis. CONCLUSIONS: Transplant recipients are vulnerable to developing tuberculosis, possibly influenced by their immunocompromised status, solid organ transplant type, age, and community prevalence of tuberculosis. Tuberculosis prevalence by country, transplant type, and age should be considered to establish an appropriate tuberculosis prevention strategy for high-risk groups.

Higher participation rates for specific health checkups are associated with a lower incidence of treated ESKD in Japan.

BACKGROUND: A Japanese cohort study previously reported that not attending health checkups was associated with an increased risk of treated end-stage kidney disease (ESKD). The present study aimed to examine this association at the prefecture level. METHODS: We conducted an ecological study of all prefectures in Japan (n = 47) using five sources of nationwide open data. We explored associations of participation rates for Specific Health Checkups (SHC participation rates), the estimated prevalence of chronic kidney disease (CKD), and the ratio of nephrology specialists for each prefecture with prefecture-specific standardized incidence rates (SIRs) of treated ESKD using structural equation modeling. RESULTS: Prefecture-specific SHC participation rates ranged from 44.2% to 65.9%, and were negatively correlated with prefecture-specific SIRs and prevalence of CKD, and positively correlated with the ratio of nephrology specialists. SHC participation rates had significant negative effects on prefecture-specific SIRs (standardized estimate (ß) = - 0.38, p = 0.01) and prefecture-specific prevalence of CKD (ß = - 0.32, p = 0.02). Through SHC participation rates, the ratio of nephrology specialists had a significant indirect negative effect on prefecture-specific SIRs (ß= - 0.14, p = 0.02). The model fitted the data well and explained 14% of the variance in SIRs. CONCLUSIONS: Our findings support the importance of increasing SHC participation rates at the population level and may encourage people to undergo health checkups.

A population level analysis of second hematological malignancies in chronic lymphocytic leukemia/small lymphocytic lymphoma survivors in the era of targeted therapies.

With improvement in survival after chronic lymphocytic leukemia (CLL) diagnosis, the real-world burden of second hematological malignancies (SHM) has not been comprehensively assessed in recent era. We analyzed risk, incidence, and outcomes of SHM in CLL patients between 2000 and 2019 using SEER database. CLL patients had greater risk for hematological malignancies than general population [SIR, standardized incidence ratio (95% CI):2.58 (2.46-2.70); p < 0.05]. The risk for subsequent lymphoma increased by 1.75 folds in 2015-2019 compared to 2000-2004. The duration, after CLL diagnosis, of maximum risk for SHM decreased as 60-119 months for time-period 2000-2004, 6-11 months for 2005-2009 to 2-5 months for 2010-2014 and 2015-2019. Incidence of SHM was 2.5% in CLL survivors (1736/70,346) with lymphoid SHM being more common than myeloid SHM, and DLBCL being the most common pathology (n = 610, 35% of all SHM). Male sex, age ≤65 years at CLL diagnosis, and chemotherapy treatment were associated with higher risk for SHM. The median gap between CLL and SHM diagnoses was 46 months. The median survival for de-novo-AML, t-MN, CML, and aggressive NHL was 63, 86, 95, and 96 months respectively. Although SHM remains rare, there is increased risk in recent era, likely due to improved survival in CLL patients, necessitating active surveillance strategies.

Second Primary Malignancies in Patients with a Neuroendocrine Neoplasm in England.

INTRODUCTION: Patients with neuroendocrine neoplasms (NENs) may often develop other malignancies. This study aimed to identify the frequency at which these second malignancies occurred in England. METHODS: Data were extracted from the National Cancer Registration and Analysis Service (NCRAS) on all patients diagnosed with a NEN at one of eight NEN site groups between 2012 and 2018: appendix, caecum, colon, lung, pancreas, rectum, small intestine, and stomach. WHO International Classification of Disease Edition-10 (ICD-10) codes were used to identify patients who had been diagnosed with an additional non-NEN cancer. Standardized incidence ratios (SIRs) for tumours diagnosed after the index NEN were produced for each non-NEN cancer type by sex and site. RESULTS: A total of 20,579 patients were included in the study. The most commonly occurring non-NEN cancers after NEN diagnosis were the prostate (20%), lung (20%), and breast (15%). Statistically significant SIRs were observed for non-NEN cancer of the lung (SIR = 1.85, 95% CI: 1.55-2.22), colon (SIR = 1.78, 95% CI: 1.40-2.27), prostate (SIR = 1.56, 95% CI: 1.31-1.86), kidney (SIR = 3.53, 95% CI: 2.72-4.59), and thyroid (SIR = 6.31, 95% CI: 4.26-9.33). When stratified by sex, statistically significant SIRs remained for the lung, renal, colon, and thyroid tumours. Additionally, females had a statistically significant SIR for stomach cancer (2.65, 95% CI: 1.26-5.57) and bladder cancer (SIR = 2.61, 95% CI: 1.36-5.02). CONCLUSION: This study found that patients with a NEN experienced a metachronous tumour of the lung, prostate, kidney, colon, and thyroid at a higher rate than the general population of England. Surveillance and engagement in existing screening programmes are required to enable earlier diagnosis of second non-NEN tumours in these patients.

Unfavorable cancer mortality-to-incidence ratios in patients with schizophrenia: A nationwide cohort study in Taiwan, 2000-2019.

OBJECTIVES: Studies on cancer incidence and mortality in patients with schizophrenia have reported inconsistent findings. In this study, we simultaneously investigated cancer incidence and mortality in patients with schizophrenia and evaluated the cancer mortality-to-incidence ratio (MIR), which is rare in the literature. METHODS: From the Taiwan National Health Insurance Database, we collected the data of 107,489 patients who received a diagnosis of schizophrenia between 2000 and 2019. Data regarding cancer incidence and mortality were obtained from the Taiwan Cancer Registry and National Mortality Database, respectively. In total, 3881 incident cancer cases and 2288 cancer mortality cases were identified. Standardized incidence ratios (SIRs), mortality rate ratios (MRRs), and MIRs were compared between patients with schizophrenia and the general population. RESULTS: The overall rate of cancer incidence was slightly lower (SIR: 0.95; 95% confidence interval [CI]: 0.92-0.98; p < 0.001) and that of cancer mortality was higher (MRR: 1.29; 95% CI: 1.23-1.3; p < 0.001) in patients with schizophrenia than in the general population. The MIR for overall cancer was significantly higher in the patients with schizophrenia. The relative MIR (MIR of patients with schizophrenia divided by that of the general population) was 1.36 (95% CI: 1.30-1.42). CONCLUSION: The MIR was significantly higher in the patients with schizophrenia than in the general population, indicating the possible presence of healthcare disparities. Additional studies are required to investigate the potential association between the significantly higher MIR in patients with schizophrenia and healthcare disparities.

Long-term risk of cancer among the first-degree relatives of epithelial ovarian cancer patients: A cohort study with 48 years of follow up.

INTRODUCTION: The long-term risk of cancer among first-degree relatives of ovarian cancer patients, especially their offspring, is of apparent clinical importance. Risks caused by known inherited factors such as BRCA1 or BRCA2 pathogenic variants are well established, but these account for only about 15% of ovarian cancer cases. Less is known about the possible familial risks of sporadic ovarian cancers. MATERIAL AND METHODS: Using registry data, we conducted a retrospective cohort study with a total of 6501 first-degree relatives of 559 epithelial ovarian cancer patients. We studied the occurrence of overall cancer and cancer in specific sites known or suspected to be associated with ovarian cancer (breast, cervix, colon, endometrium, lung and trachea, skin melanoma, ovary, pancreas, prostate, rectum, and stomach). RESULTS: The overall number of cancers was not increased among the first-degree relatives of epithelial ovarian cancer patients during the up to 48 years of follow up. Among female relatives, the standardized incidence ratio for ovarian cancer was 1.92 (95% CI 1.27-2.79), mostly explained by a 2.30-fold (95% CI 1.46-3.45) risk among the patients' sisters. There was a decreasing trend in the standardized incidence ratio for ovarian cancer among patients' sisters by increasing age of the index patient. CONCLUSIONS: In our study cohort, we did not observe an increase in the overall cancer risk among the first-degree relatives of epithelial ovarian cancer patients in comparison with the general population. The risk for ovarian cancer, however, was increased. Current recommendations suggest prophylactic removal of the fallopian tubes and ovaries only with identified inherited risk factors. Our results emphasize the role of genetic counseling and testing, particularly in young ovarian cancer patients and their close female relatives.

Prefecture-specific prevalence of overweight/obesity is associated with regional variation in the incidence of treated ESKD in Japan.

BACKGROUND: Overweight/obesity is a significant risk factor for chronic kidney disease and end-stage kidney disease (ESKD) in the general population. This study evaluated the impact of sex- and prefecture-specific prevalence of overweight/obesity on standardized incidence rates (SIRs) of treated ESKD in Japan. METHODS: We conducted an ecological study of all prefectures in Japan (n = 47) using data from the Japanese Society of Dialysis Therapy, national census, the NDB Open Data, and the Statistics of Physicians, Dentists and Pharmacists. We calculated the prevalence of overweight/obesity and proteinuria, standardized mortality ratio, and ratio of nephrology specialists for each prefecture, and explored associations of these variables with sex- and prefecture-specific SIRs of treated ESKD using bivariate association analysis, multiple regression analysis, and structural equation modeling (SEM). RESULTS: Prefecture-specific SIRs ranged from 0.72 to 1.24 for men and 0.69-1.41 for women. Prefecture-specific SIRs were significantly correlated with both the prevalence of overweight/obesity and prevalence of proteinuria. The prevalence of overweight/obesity showed direct, positive, and significant associations with prefecture-specific SIRs in men (standardized estimate (ß) = 0.43, p < 0.001) and women (ß = 0.40, p < 0.001). The prevalence of proteinuria showed a significant association with prefecture-specific SIRs only in women (ß = 0.33, p = 0.01). The SEM models explained 26% of the variance in SIR for men and 28% for women. CONCLUSIONS: Our findings provide evidence that the prefecture-specific prevalence of overweight/obesity in Japan can explain regional variation in prefecture-specific SIRs of treated ESKD in both sexes.

Trends in risks of malignancies in Japanese patients with rheumatoid arthritis: Analyses from a 14-year observation of the IORRA cohort.

OBJECTIVES: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). METHODS: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. RESULTS: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. CONCLUSIONS: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA.

Cancer risk and mortality after solid organ transplantation: A population-based 30-year cohort study in Finland.

Cancer is a significant cause of morbidity and mortality after solid organ transplantation (SOT) and related to lifelong immunosuppression. This retrospective registry study assessed for the first time in Finland population-based cancer risk and cancer mortality after all SOTs (lung and childhood transplantations included) as standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs). Data from transplant registries were linked with the data of Finnish Cancer Registry and Statistics Finland. We followed 6548 consecutive first SOT recipients from 1 January 1987 to 31 December 2016 translating to 66 741 person-years (median follow-up time 8.9 years [interquartile range 4.0-15.1]). In total, 2096 cancers were found in 1483 patients (23% of all patients). Majority of cancers (53%) were nonmelanoma skin cancers (NMSCs). The overall SIR was 3.6 (95% confidence interval [CI]: 3.5-3.8) and the SIR excluding NMSCs was 2.2 (95% CI: 2.0-2.3). SIR for all cancers was highest for heart (5.0) and lowest for liver (2.7) recipients. Most common cancer types after NMSCs were non-Hodgkin lymphoma (NHL), SIR 9.9 (95% CI: 8.5-11.4) and kidney cancer, SIR 7.3 (95% CI: 6.0-8.8). Cancer-related deaths were 17% (n = 408) of all deaths after first month post transplantation. SMR for all cancers was 2.5 (95% CI: 2.2-2.7) and for NHL 13.6 (95% CI: 10.7-16.8). Notably, overall SIR for cancer was lower in later period (2000-2016), 3.0 (95% CI: 2.8-3.2), than in earlier period (1987-1999), 4.3 (95% CI: 4.0-4.5), P < .001. Decrease in cancer incidence was temporally associated with major changes in immunosuppression in the 2000s.

Inflammatory bowel disease and risk of adenocarcinoma and neuroendocrine tumors in the small bowel.

BACKGROUND: Uncertainty prevails about the magnitude of excess risk of small bowel cancer in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: To quantify the risk of small bowel adenocarcinoma and neuroendocrine tumors in patients with ulcerative colitis (UC) and Crohn's disease (CD), we undertook a population-based cohort study of all patients with IBD diagnosed in Norway and Sweden from 1987 to 2016. Patients were followed through linkage to national registers. We calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) of small bowel adenocarcinomas and neuroendocrine tumors for patients with CD and UC. We excluded the first year of follow-up to reduce reverse causality. RESULTS: Among 142 008 patients with a median follow-up of 10.0 years, we identified 66 adenocarcinomas and 57 neuroendocrine tumors in the small bowel. The SIR of small bowel adenocarcinoma was 8.3 (95% CI 5.9-11.3) in CD and 2.0 (95% CI 1.2-3.1) in UC. The incidence rates of adenocarcinomas were highest in CD with stricturing disease and extent limited to the small bowel, at 14.7 (95% CI 8.2-24.2) and 15.8 (95% CI 8.4-27.0) per 100 000 person-years, respectively. The SIR of neuroendocrine tumors was 2.5 (95% CI 1.5-3.9) in CD and 2.0 (95% CI 1.4-2.8) in UC. CONCLUSIONS: Patients with CD experienced an eightfold increased risk of small bowel adenocarcinomas, patients with both UC and CD experienced an about twofold increased risk of neuroendocrine tumors, and patients with UC experienced a twofold increased risk of small bowel adenocarcinoma. The small absolute excess cancer risk suggests that active surveillance to diagnose small intestinal cancer early is unlikely to be cost-effective.

Cancer risk in patients with migraine: A population-based cohort study in Denmark.

OBJECTIVE: The purpose of this study was to examine overall and site-specific cancer risk among individuals diagnosed with migraine compared with the general population. BACKGROUND: Current evidence regarding migraine and risk of cancer is sparse and inconclusive. METHODS: We conducted a nationwide population-based cohort study with data collected routinely and prospectively from Danish population-based registries from 1995 to 2017. We computed the age- and sex-standardized incidence ratio (SIR) as the ratio of observed to expected cancers among patients diagnosed with migraine in the study population overall, and by encounter type of first diagnosis (inpatient, outpatient specialty clinic, and emergency department). Site-specific cancers were grouped according to etiology. RESULTS: We identified 72,826 patients with a first-time hospital migraine diagnosis. There were 3090 observed overall cancer cases among individuals diagnosed with migraine as compared with 3108 expected cases (SIR 0.99, 95% confidence interval [CI]: 0.96-1.03). The cumulative incidence of all cancers combined from 1995 to 2017 among those with a first-time migraine diagnosis was 9.47% (95% CI: 9.08-9.87). The SIRs for most cancers were consistent with absence of an association: 1.00 (95% CI: 0.94-1.06) for hormone-related cancers, 0.96 (95% CI: 0.88-1.03) for smoking-related cancers, 1.10 (95% CI: 0.98-1.24) for hematologic cancers, and 0.95 (95% CI: 0.85-1.06) for immune-related cancers. Exceptions were SIRs for gastrointestinal cancers (0.78, 95% CI: 0.70-0.87) and for cancers of neurological origin (1.57, 95% CI: 1.40-1.76). CONCLUSIONS: For most cancer groups, our results did not support an association with migraine. The exceptions were an increased risk for cancers of neurological origin and a decreased risk for gastrointestinal cancers. These findings may reflect a true difference in risk among individuals with migraine, or more plausibly they reflect other forces, such as differences in medication use, detection bias and reverse causation, or shared risk factors.

Patients with Early-Onset Colorectal Cancer Have an Increased Risk of Second Primary Malignancy.

BACKGROUND: While overall colorectal cancer (CRC) rates in the USA are declining, the incidence of early-onset CRC (eoCRC) under age 50 is increasing. The aim of this study was to examine the risk of a second primary malignancy (SPM) in individuals with eoCRC, and how this risk compares to those with late-onset CRC (loCRC). METHODS: We used data from the Surveillance, Epidemiology, and End Results Program database to examine the risk of SPM after a diagnosis of eoCRC. Standardized incidence ratios (SIR) were used to estimate the risk of SPM after eoCRC and loCRC in comparison with the risk of malignancy in the general population. RESULTS: Compared to the general population, individuals with eoCRC, but not loCRC, had an increased lifetime risk of SPM (SIR 1.42, 95% CI 1.37-1.48 and SIR 1.00, 95% CI 0.99-1.02, respectively), and locations at highest risk were the small intestine, ureter, rectum, and colon. The risk of SPM after eoCRC was similar in men and women, but higher in non-whites compared to whites and higher in those with a lower area-level median household income. The risk of SPM following eoCRC was high in the first 5 years after diagnosis (SIR 2.44, 95% CI 2.24-2.66) and, in a birth cohort analysis, was found to be increasing over time. CONCLUSIONS: Individuals with eoCRC have a lifetime risk of SPM nearly 50% higher than the general population. The risk of SPM is highest in the first 5 years after diagnosis and is increasing over time.

Recent trends in the morbidity and mortality in patients with familial adenomatous polyposis: a retrospective single institutional study in Japan.

BACKGROUND: This study aimed to assess current trends in morbidity and mortality among patients with familial adenomatous polyposis (FAP). These data can be used for optimal surveillance and management of such patients. METHODS: Data (November 2001 and April 2020) of genetically confirmed patients with FAP (n = 87) and their first-degree relatives with FAP phenotype (n = 20) were extracted from the Saitama Medical Center database. Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were estimated using indirect method. RESULTS: Overall, 46 men and 61 women were included; the median age at FAP diagnosis was 28.0 years for both. The SMR for all causes of death was 47.7 (95% confidence interval [CI] 19.1-98.2) in women and 26.5 (95% CI 9.73-57.8) in men. The SIR for colorectal cancer (CRC) was 860 (95% CI 518-1340) in women and 357 (95% CI 178-639) in men. The SMR for CRC was 455 (95% CI 93.7-1330) in women and 301 (95% CI 62.0-879) in men. Thirteen patients died during the observation period, and CRC was the leading cause of death (46%). Other causes of death included desmoid tumor (n = 2), small intestinal cancer (n = 2), ovarian cancer (n = 1), duodenal cancer (n = 1), and sepsis (n = 1). CONCLUSIONS: The mortality ratio, estimated using SMR, remained high. CRC was the leading cause of death, whereas almost half of the causes of deaths were extra-colonic tumors. Life-long management of extra-colonic diseases may improve the prognosis in these patients.

Standardized incidence ratios of malignant neoplasms among patients with pneumoconiosis.

BACKGROUND: Patients with pneumoconiosis, such as silicosis and asbestosis, have a high risk of lung cancer. However, whether these patients are at high risk for neoplasms other than lung cancer and mesothelioma remains inconclusive. AIMS: To examine whether patients with pneumoconiosis have a higher incidence of malignant neoplasms other than lung cancer. METHODS: We conducted a cohort study using the medical records of patients with pneumoconiosis who visited our two hospitals from 1 January 1991 through 31 December 2017. We identified the occurrence of malignant neoplasms and calculated the incidences and standardized incidence ratios (SIRs) compared with those of the general population. RESULTS: One hundred and seventy patients with pneumoconiosis (163 men, 7 women) including 142 patients with silicosis, 24 with asbestosis and 4 with pneumoconiosis were identified. The mean age was 66.8 years. The proportion of smokers was 79%. Forty-seven malignant neoplasms occurred. Most malignant neoplasms were lung cancer (n = 22), while some were digestive cancers such as gastric cancer (n = 9), oesophageal cancer (n = 3) and colorectal cancer (n = 3). Participants presented increased risks for lung cancer (SIR: 10.86, 95% confidence interval [CI]: 7.15-16.49), gastric cancer (SIR: 2.55, 95% CI: 1.22-5.35) and oesophageal cancer (SIR: 5.78, 95% CI: 1.86-17.92). CONCLUSIONS: Compared with the general population, patients with pneumoconiosis had an increased risk of malignant neoplasms of the digestive system in addition to lung cancer. Clinicians should consider testing for digestive system cancers as well as for lung cancers in these patients.

Differences in the prevalence of locomotive syndrome and osteoporosis in Japanese urban and rural regions: The Kashiwara and Yakumo studies.

OBJECTIVES: To clarify whether the prevalence of locomotive syndrome (LS) and osteoporosis differed according to region, gender, and physical functions in Japan. METHODS: Data were collected in Kashiwara City (urban region) and Yakumo Town (rural region). Totally, 208 participants from the urban region and 782 participants from the rural region were included in this study. LS was assessed using the 25-item Geriatric Locomotive Function Scale and osteoporosis was assessed using a quantitative ultrasound. Physical functions were measured using grip strength and the 3-m timed up-and-go test. Differences between urban and rural regions were investigated using standardized incidence ratio and multivariate analysis. RESULTS: The prevalence of LS and osteoporosis was 24.5% and 42.8% in the urban region and 10.9% and 28.8% in the rural region, respectively. The standardized incidence ratio of the urban region versus the rural region was 1.80 (95% confidence intervals [CI] = 1.35-2.39) for LS and 1.21 (95% CI = 1.32-2.43) for osteoporosis, showing that the prevalence of LS was significantly higher in the urban region. Multivariate analysis indicated that LS was significantly associated with the urban sample and timed up-and-go was significantly longer in the urban sample. CONCLUSION: Regional differences may be considered when evaluating LS in health checkups. Understanding the results of this study may help reduce LS prevalence.

Cancer incidence among musicians: 45 years of follow-up in four Nordic countries.

BACKGROUND: There are studies suggesting that participation in musical activities may protect from cancer. On the other hand, some musicians have a lifestyle that might increase the risk of cancer. The objective of this study was to assess the cancer pattern of musicians in four Nordic countries. MATERIAL AND METHODS: This study combines census and cancer registry data from 1961 to 2005 for 13 million people from Finland, Iceland, Norway, and Sweden. Standardized incidence ratio (SIR) analyses were conducted with the cancer incidence rates for entire national populations used as reference rates. RESULTS: There were 11,401 male and 3105 female musicians with 2039 cancer cases. The SIR for all sites combined was 1.02 (95% confidence interval 0.97-1.07) in men and 1.04 (0.94-1.15) in women. In male musicians, there were statistically significant excesses in oropharyngeal cancer (4.36, 2.73-6.60), esophageal cancer (2.08, 1.51-2.81), liver cancer (1.81, 1.26-2.52), and skin melanoma (1.40, 1.10-1.75). The risk was decreased in lip cancer (0.13, 0.02-0.48), stomach cancer (0.66, 0.50-0.82), and lung cancer (0.77, 0.65-0.90). In female musicians, there were no statistically significant SIRs in any of the cancer types studied, but the risk of breast cancer was significantly elevated in the age category of 70+ (1.52, 1.04-2.15). The overall SIR was stable over the 45 year period of observation, but strong decreases were observed in the SIRs of esophageal cancer, liver cancer, laryngeal cancer, and skin melanoma. CONCLUSION: Musicians have characteristics of indoor workers such as low incidence of lip cancer and high incidence of skin melanoma. The low incidence of lung cancer suggests that the prevalence of smoking among musicians is lower than in the general population while the elevated risk of alcohol-related cancer types suggest that drinking is likely more common among musicians. The cancer risk for all sites combined is still similar to that of the general population in the four countries studied.

Long-term observational study on 6223 survivors of arsenic poisoning due to contaminated milk powder during infancy.

In 1955, an outbreak of arsenic poisoning caused by the ingestion of arsenic-contaminated Morinaga Dry Milk occurred in western Japan. This study aimed to assess the mortality and cancer incidence risk among Japanese individuals who were poisoned during this time as infants. In total, 6223 survivors (mean age at enrollment, 27.5 y) who had ingested contaminated milk when they were aged ≤ 2 y participated in this study. Follow-up was conducted from 1982 to 2018 (mean follow-up duration, 30.3 y). Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) were used to compare mortality and cancer incidence rates of subjects with the respective Japanese population rates, and 95% confidence intervals (95% CIs) of the SMR and SIR were also calculated. In total, 561 deaths and 524 new cancer cases were observed. A statistically significant increase in mortality rate was observed for all causes (SMR, 1.15; 1.01-1.19), nervous system disease (2.83, 1.62-4.19), respiratory disease (2.02, 1.37-2.62), genitourinary system disease (2.25, 1.10-3.73), and traffic accident (2.03, 1.14-3.04). In contrast, a significant decrease in cancer incidence rate was observed for all cancers (SIR, 0.96; 0.84-0.99), stomach cancer (0.77, 0.57-0.92), colon cancer (0.63, 0.41-0.85), rectum cancer (0.69, 0.43-0.95), and breast cancer (0.72, 0.52-0.89). Liver cancer showed a high mortality rate (SMR, 1.68; 1.06-2.31). In this study, after the long-term follow-up we revealed overall and cause-specific mortality and cancer incidence risk among survivors who ingested arsenic-contaminated dry milk as infants.

Melanoma Risk is Increased in Patients with Mycosis Fungoides Compared with Patients with Psoriasis and the General Population.

Patients with mycosis fungoides (MF) are thought to be at increased risk of melanoma. However, studies addressing surveillance-bias and treatments as a possible confounder are lacking. This retrospective study compared the prevalence and risk of melanoma between 982 patients with MF, and 3,165 patients with psoriasis attending tertiary cutaneous-lymphoma/psoriasis clinics during 2009 to 2018. Melanoma was diagnosed in 47 patients with MF (4.8%; 43 early-stage) and in 23 patients with psoriasis (0.7%) (odds ratio 6.6, p < 0.0001). In 60% of patients, MF/psoriasis preceded melanoma diagnosis. Hazard ratio (HR) for a subsequent melanoma in MF vs psoriasis was 6.3 (95% confidence interval (95% CI) 3.4-11.7, p < 0.0001). Compared with the general population, melanoma standardized incidence ratios were 17.5 in patients with MF (95% CI 11.0-23.9, p < 0.0001), and 2.2 (95% CI 0.6-3.8, p = 0.148) in patients with psoriasis. Narrow-band ultraviolet B was not a contributory factor (HR 1.15, 95% CI 0.62-2.14, p = 0.66). These findings add evidence that patients with MF have a significantly higher risk of melanoma, not only compared with the general population, but also compared with patients with psoriasis. This comorbidity may be inherent to MF.

Evaluation for Kienböck Disease Familial Clustering: A Population-Based Cohort Study.

PURPOSE: Kienböck disease (KD) is rare and its etiology remains unknown. As a result, the ideal treatment is also in question. Our primary purpose was to test the hypothesis that KD would demonstrate familial clustering in a large statewide population with comprehensive genealogical records, possibly suggesting a genetic etiologic contribution. Our secondary purpose was to evaluate for associations between KD and known risk factors for avascular necrosis. METHODS: Patients diagnosed with KD were identified by searching medical records from a comprehensive statewide database, the Utah Population Database. This database contains pedigrees dating back to the early 1800s, which are linked to 31 million medical records for 11 million patients from 1996 to the present. Affected individuals were then mapped to pedigrees to identify high-risk families with an increased incidence of KD relative to control pedigrees. The magnitude of familial risk of KD in related individuals was calculated using Cox regression models. Association of risk factors related to KD was analyzed using conditional logistic regression. RESULTS: We identified 394 affected individuals linked to 194 unrelated high-risk pedigrees with increased incidence of KD. The relative risk of developing KD was significantly elevated in first-degree relatives. There was a significant correlation between alcohol, glucocorticoid, and tobacco use and a history of diabetes, and the diagnosis of KD. CONCLUSIONS: Familial clustering of KD observed in the Utah Population Database cohort indicates a potential genetic contribution to the etiology of the disease. Identification of causal gene variants in these high-risk families may provide insight into the genes and pathways that contribute to the onset and progression of KD. CLINICAL RELEVANCE: This study suggests that there is a potential genetic contribution to the etiology of KD and that the disease has a significant association with several risk factors.