Risk and Prognosis of Cancer in Patients With Cerebral Venous Thrombosis Compared With the Danish General Population.

BACKGROUND: Whether cerebral venous thrombosis (CVT) is a marker of cancer in clinical practice remains unknown. Little is known about the prognosis of cancer detected subsequent to CVT. METHODS: We used Danish nationwide registries (1996-2019) to identify patients with a first-time primary inpatient diagnosis of CVT without a history of cancer (N=811, 65% women, median age 42 years). We assessed the risk of an incident cancer diagnosis using standardized incidence ratios (SIRs). This measure contrasts the number of observed cancers among patients with CVT to the number of expected cancers where patients with CVT have the same cancer risk as the general population. We used Kaplan-Meier survival analysis and Cox regression to compare the survival of patients with both cancer and CVT with the survival of patients with cancer but without CVT, matched on cancer site, sex, age, and year of cancer diagnosis. RESULTS: Observing 43 incident cancer cases during follow-up, the overall SIR was unity (SIR, 1.04 [95% CI, 0.75-1.40]). However, the risk was ≈7-fold the expected level in the first 3 months following CVT diagnosis (SIR, 7.00 [95% CI, 3.02-13.80]) and ≈2-fold the expected level from 3 to 12 months following CVT diagnosis (SIR, 2.21 [95% CI, 0.89-4.56]). By 12 months following CVT diagnosis, the risk resembled the expected level (SIR, 0.76 [95% CI, 0.50-1.09]). Survival among cancer patients with prior CVT versus cancer patients without prior CVT was 91% versus 87% after 6 months and 65% versus 70% after 5 years. The adjusted hazard ratio of death was 0.78 (95% CI, 0.44-1.38). CONCLUSIONS: Patients with CVT were not at overall increased risk of a cancer diagnosis, except in the first 3 months after diagnosis during which period the risk was elevated ≈7-fold. The estimate from this early period, however, was based on only a few cancer diagnoses. Unlike other forms of venous thrombosis, a prior diagnosis of CVT did not negatively impact cancer survival.

Increased Cancer Risk in Patients with Kidney Disease and Venous Thromboembolism: A Population-Based Cohort Study.

BACKGROUND: Venous thromboembolism (VTE) may be a harbinger of cancer in the general population. Patients with kidney disease have an a priori increased VTE risk. However, it remains unknown how a VTE affects subsequent cancer risk in these patients. OBJECTIVES: To examine the cancer risk in patients with kidney disease following a VTE. METHODS: We conducted a nationwide population-based cohort study in Denmark (1996-2017), including all VTE patients with a diagnosis of kidney disease. We calculated absolute risks of cancer (accounting for competing risk of death) and age-, sex-, and calendar-period standardized incidence ratios (SIRs) comparing the observed cancer incidence with national cancer incidence rates and cancer incidence rates of VTE patients without kidney disease. RESULTS: We followed 3,362 VTE patients with kidney disease (45.9% females) for a median follow-up time of 2.4 years (interquartile range: 0.6-5.4). During follow-up, 464 patients were diagnosed with cancer, of whom 169 (36.4%) were diagnosed within the first year. The 1-year absolute risk of any cancer was 5.0% (95% confidence interval [CI]: 4.3-5.8), with a SIR of 2.9 (95% CI: 2.5-3.4) when compared with the general population, and 2.0 (95% CI: 1.8-2.4) when compared with VTE patients without kidney disease. During subsequent years of follow-up, the SIRs declined to 1.5 (95% CI: 1.3-1.6) when compared with the general population, and 1.1 (95% CI: 0.9-1.2) compared with VTE patients without kidney disease. CONCLUSION: Patients with hospital-diagnosed kidney disease have increased cancer risk after VTE, especially within the first year following the VTE diagnosis.

Cancer Diagnosis and Prognosis After Guillain-Barré Syndrome: A Population-Based Cohort Study.

Introduction: It is unclear whether Guillain-Barré syndrome (GBS) can be a marker of a paraneoplastic syndrome. We examined whether GBS is associated with cancer and whether the prognosis of GBS patients with cancer differs from that of other cancer patients. Materials and Methods: We conducted a population-based cohort study of patients diagnosed with GBS between 1978 and 2017 using Danish registry-data. Main outcome measures were cancer incidence and mortality after cancer diagnosis. We calculated absolute risks of a cancer diagnosis, treating death as competing risk, and standardized incidence ratios (SIRs) as measures of relative risk. We matched each GBS cancer patient with up to 10 cancer patients without a GBS diagnosis and examined the six-month survival after cancer diagnosis using Cox regression analysis. Results: We identified 7897 patients (58% male, median age 57 years) with GBS. During a median follow-up of 9.5 years, the one-year risk of cancer was 2.7% (95% confidence interval (CI), 2.4-3.1). The SIR was increased throughout follow-up, but most noticeably during the first year after diagnosis (SIR: 3.35, 2.92-3.83). SIRs were particularly elevated for hematologic cancers (SIR: 8.67, 6.49-11.34), smoking-related cancers (SIR: 3.57, 2.81-4.47), and cancers of neurological origin (SIR: 8.60, 5.01-13.77). Lung cancer was the main contributor to the overall excess risk, which persisted after 36 months of follow-up (SIR: 1.17, 1.09-1.25). The mortality rate ratio comparing patients diagnosed with any cancer within one year of their GBS diagnosis and matched GBS-free cancer cohort members was 1.56 (95% CI, 1.27-1.90). Conclusion: GBS patients had a three-fold increased risk of cancer diagnosis in the first year of follow-up. The absolute cancer risk was almost 3.0%. A GBS diagnosis was an adverse prognostic marker for survival following cancer diagnosis. Clinicians should consider occult cancer in patients hospitalized with GBS.

Cancer Risk in Pulmonary Hypertension Patients.

BACKGROUND: Strong evidence indicates that venous thromboembolism is a presenting symptom of cancer. Cancer is a known cause of pulmonary hypertension; however, it remains unknown whether pulmonary hypertension is a marker of occult cancer. We examined the association between a pulmonary hypertension diagnosis and cancer risk in a cohort study using population-based data from the Danish health system. PATIENTS AND METHODS: Using Danish nationwide registries, we identified 6335 patients with a pulmonary hypertension diagnosis and without a previous cancer diagnosis between 1995 and 2017. We computed the age-, sex-, and calendar year-standardized incidence ratio (SIR) as the ratio of observed to expected number of cancers using national incidence rates as the reference. We performed a subgroup analysis among patients with chronic thromboembolic pulmonary hypertension in the period in which a specific ICD-10 code was available (2006-2017). RESULTS: We identified 212 cancers within the first year of follow-up and 796 cancers thereafter. The one-year risk of cancer was 3.3% and the one-year SIR was 1.96 (95% confidence interval [CI]: 1.70-2.23). In the second and subsequent years, the SIR remained elevated (SIR: 1.15 [95% CI: 1.08-1.24]). In patients with chronic thromboembolic pulmonary hypertension, the one-year SIR was 1.41 (95% CI: 0.82-2.25). CONCLUSION: Cancer risk was clearly higher in patients with pulmonary hypertension compared with the general population. The association was particularly strong in the first year of follow-up, but remained elevated thereafter. However, absolute risks were low, limiting the clinical relevance of pursuing early cancer detection in these patients.

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.

Fever of Unknown Origin and Incidence of Cancer.

BACKGROUND: Diagnostic tools for determining causes of fever of unknown origin (FUO) have improved over time. We examined if cancer incidence among these patients changed over a 20-year period. METHODS: Population-based cohort study using nationwide Danish registries. We identified individuals diagnosed with FUO (1998-2017) to quantify their excess risk of cancer compared with the general population. Follow-up for cancer started 1 month after FUO. We computed absolute risks and standardized incidence ratios (SIRs) of cancer, and mortality rate ratios adjusted for age, sex, and cancer stage. RESULTS: Among 6620 patients with FUO (46.9% male; median age: 39 years), 343 were diagnosed with cancer (median follow-up: 6.5 years). The 1- to <12-month risk was 1.2%, and the SIR was 2.3 (95% CI, 1.8-2.9). The increased 1- to <12-month SIR was mainly due to an excess of Hodgkin lymphoma (SIR = 41.7) non-Hodgkin lymphoma (SIR = 16.1), myelodysplastic syndrome/chronic myeloproliferative diseases (SIR = 6.0), lower gastrointestinal cancer (SIR = 3.3), and urinary tract cancer (SIR = 2.9). Beyond 1-year follow-up, malignant melanoma, hepatobiliary tract/pancreatic cancer, and brain/CNS/eye cancer were diagnosed more often than expected. The 1- to <12-month cancer SIR attenuated over time, and for the 2013-2017 period we found no excess risk. Patients diagnosed with cancer ≤1 year after FUO had similar mortality to cancer patients without this diagnosis. CONCLUSIONS: Patients with FUO have a higher 1- <12-month cancer SIR; thereafter, the incidence for most cancers equals that of the general population. Decreasing SIRs over time suggests improvements in the initial diagnostic workup for FUO.

Acute urinary retention and risk of cancer: population based Danish cohort study.

OBJECTIVE: To examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention. DESIGN: Nationwide population based cohort study. SETTING: All hospitals in Denmark. PARTICIPANTS: 75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017. MAIN OUTCOME MEASURES: Absolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population. RESULTS: The absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years. CONCLUSIONS: Acute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause.

Venous thromboembolism and risk of cancer in users of statins: A Danish population-based cohort study.

BACKGROUND: Venous thromboembolism (VTE) may be the first symptom of cancer. Statins are suggested to prevent VTE, but the risk of cancer in VTE patients using statins remains poorly understood. OBJECTIVES: To examine if VTE is a marker of cancer in users of statins. METHODS: We identified all Danish patients during 1996-2017 with a first-time diagnosis of VTE and a filled prescription for a statin within 90 days prior to the VTE diagnosis. We classified patients as prevalent users if the first filling of a statin occurred more than one year preceding the VTE diagnosis, and as new users if the first filling occurred within the preceding year. We computed cumulative incidences of cancer, with death as a competing risk, and age-, sex-, and calendar-period standardized incidence ratios (SIRs), comparing the observed cancer incidence with the expected based on national cancer statistics. RESULTS: Among 9280 (85%) prevalent users of statin and 1580 (15%) new users, the one-year cumulative incidence of any cancer was 6.6 (95% CI: 6.1-7.2) for prevalent users and 6.4 (95% CI: 5.2-7.6) for new users; the corresponding SIRs were 3.1 (95% CI: 2.9-3.3) and 3.5 (95% CI: 2.9-4.3). In the second and subsequent years, the SIRs diminished and approached unity for both prevalent (1.1 [95% CI: 1.1-1.2]) and new users (1.1 [95% CI: 0.9-1.3]). CONCLUSIONS: VTE patients using statins had a 3-fold increased rate of cancer in the first year after diagnosis. A first VTE serves as an important marker of cancer, regardless of statin use.

Motor Neuron Disease and Risk of Cancer: A Population-Based Cohort Study in Denmark.

BACKGROUND: Some neurogenerative diseases have been linked to a reduced risk of cancer, but the association between motor neuron disease and cancer risk is not well understood. We hypothesized that cancer risk would be lower among those with motor neuron disease and its most common subtype, amyotrophic lateral sclerosis. METHODS: We conducted a population-based cohort study of motor neuron disease and cancer risk using routinely collected data from population-based registries in Denmark. We examined cancer incidence among patients diagnosed with motor neuron disease between January 1980 and December 2013 followed through 2013. Using Danish national cancer rates for the study period, we computed standardized incidence ratios as a measure of relative risks. RESULTS: In the cohort of 5053 patients with a motor neuron disease, the overall standardized incidence ratio of any cancer was 1.17 (95% confidence interval [CI], 1.03-1.31); the corresponding standardized incidence ratio for amyotrophic lateral sclerosis was 1.24 (95% CI, 0.96-1.57). The standardized incidence ratios of any cancer in the cohort with motor neuron disease was 1.52 (95% CI, 1.22-1.87) for <1 year of follow-up; 0.87 (95% CI, 0.68-1.09) for years 1-5 of follow-up; and 1.22 (95% CI, 1.01-1.46) for >5 years of follow-up. Beyond one year of follow-up, patients in the motor neuron disease had elevated standardized incidence ratios for lymphoid leukemia, non-Hodgkin lymphoma, and basal cell skin cancer. CONCLUSION: Findings fail to support the hypothesis that motor neuron disease or amyotrophic lateral sclerosis is associated with reduced cancer incidence. An elevated risk of cancer during the first year of follow-up may be attributable to heightened surveillance.

Risk of primary urological and genital cancers following incident breast cancer: a Danish population-based cohort study.

PURPOSE: The prevalence of breast cancer survivors has increased due to dissemination of population-based mammographic screening and improved treatments. Recent changes in anti-hormonal therapies for breast cancer may have modified the risks of subsequent urological and genital cancers. We examine the risk of subsequent primary urological and genital cancers in patients with incident breast cancer compared with risks in the general population. METHODS: Using population-based Danish medical registries, we identified a cohort of women with primary breast cancer (1990-2017). We followed them from one year after their breast cancer diagnosis until any subsequent urological or genital cancer diagnosis. We computed incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as the observed number of cancers relative to the expected number based on national incidence rates (by sex, age, and calendar year). RESULTS: Among 84,972 patients with breast cancer (median age 61 years), we observed 623 urological cancers and 1397 genital cancers during a median follow-up of 7.4 years. The incidence rate per 100,000 person-years was stable during follow-up (83 for urological cancers and 176 for genital cancers). The SIR was increased for ovarian cancer (1.37, 95% CI 1.23-1.52) and uterine cancer (1.37, 95% CI 1.25-1.50), but only during the pre-aromatase inhibitor era (before 2007). Moreover, the SIR of kidney cancer was increased (1.52, 95% CI 1.15-1.97), but only during 2007-2017. The SIR for urinary bladder cancer was marginally increased (1.15, 95% CI 1.04-1.28) with no temporal effects. No associations were observed for cervical cancer. CONCLUSION: Breast cancer survivors had higher risks of uterine and ovarian cancer than expected, but only before 2007, and of kidney cancer, but only after 2007. The risk of urinary bladder cancer was moderately increased without temporal effects, and we observed no association with cervical cancer.

Risk of lower gastrointestinal bleeding and colorectal neoplasms following initiation of low-dose aspirin: a Danish population-based cohort study.

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

Risk of primary gastrointestinal cancers following incident non-metastatic breast cancer: a Danish population-based cohort study.

OBJECTIVE: We examined the risk of primary gastrointestinal cancers in women with breast cancer and compared this risk with that of the general population. DESIGN: Using population-based Danish registries, we conducted a cohort study of women with incident non-metastatic breast cancer (1990-2017). We computed cumulative cancer incidences and standardised incidence ratios (SIRs). RESULTS: Among 84 972 patients with breast cancer, we observed 2340 gastrointestinal cancers. After 20 years of follow-up, the cumulative incidence of gastrointestinal cancers was 4%, driven mainly by colon cancers. Only risk of stomach cancer was continually increased beyond 1 year following breast cancer. The SIR for colon cancer was neutral during 2-5 years of follow-up and approximately 1.2-fold increased thereafter. For cancer of the oesophagus, the SIR was increased only during 6-10 years. There was a weak association with pancreas cancer beyond 10 years. Between 1990-2006 and 2007-2017, the 1-10 years SIR estimate decreased and reached unity for upper gastrointestinal cancers (oesophagus, stomach, and small intestine). For lower gastrointestinal cancers (colon, rectum, and anal canal), the SIR estimate was increased only after 2007. No temporal effects were observed for the remaining gastrointestinal cancers. Treatment effects were negligible. CONCLUSION: Breast cancer survivors were at increased risk of oesophagus and stomach cancer, but only before 2007. The risk of colon cancer was increased, but only after 2007.

Syncope as a sign of occult cancers: a population-based cohort study.

BACKGROUND: We examined if syncope was a marker of an occult cancer by comparing the risk in patients with a syncope episode with that of the general population. METHODS: Using Danish population-based medical registries, we identified all patients diagnosed with syncope during 1994-2013 and followed them until a cancer diagnosis, emigration, death or end of follow-up, whichever came first. We computed cumulative risks and standardised incidence ratios (SIR) with 95% confidence intervals (CI). RESULTS: Among 208,361 patients with syncope, 20,278 subsequent cancers were observed. The 6-month cumulative risk of any cancer was 1.2%, increasing to 17.9 % for 1-20 years of follow-up. The highest cumulative risks after 6 months of follow-up were lung cancer (0.2%), colorectal cancer (0.2%), prostate cancer (0.1%) and brain cancer (0.1%). The 6-month SIR were 2.7 (95% CI: 2.4-3.0) for lung cancer, 2.0 (95% CI: 1.8-2.2) for colorectal cancer, 1.7 (95% CI: 1.5-1.9) for prostate cancer and 10.0 (95% CI: 8.6-11.4) for brain cancer. CONCLUSIONS: Syncope was a weak marker of an occult cancer. In short-term the highest cumulative risks were observed for lung, colorectal, prostate and brain cancers. An aggressive search for occult cancer in a patient with syncope is probably not warranted.

Metastasis directed therapy for liver and lung metastases from colorectal cancer-A population-based study.

About 10-20% of patients with metastatic colorectal cancer (mCRC) are candidates for metastasis directed therapies such as surgical resection, ablation and stereotactic radiotherapy. We examined the temporal changes in use of metastasis directed therapies and established prognostic factors for survival in a nationwide cohort study. The Danish nationwide medical registries were used to retrieve data on treatment for liver and/or lung metastasis in patients with metastatic colorectal cancer in the period 2000-2013. Overall survival through 2014 was calculated from the time of treatment of metastases by Kaplan-Meier method and mortality between groups was assessed using Cox regression. We report 2,912 patients undergoing a total of 3,602 procedures with an increased use of all modalities during 14 calendar years. Median survival was 3.7 years (interquartile range (IQR) 2.0-9.7 years). In the multivariate analysis, the nodal stage of the primary tumor had the most pronounced association with survival with a hazard ratio for mortality of 1.56 (95% CI: 1.33-1.83) for N2 stage with reference to N0. Furthermore, female gender, age, comorbidity, surgical treatment, administration of chemotherapy, and left-sided primary tumors were associated with improved prognosis in the multivariate analysis.

Adjustment disorder and type-specific cancer incidence: a Danish cohort study.

BACKGROUND: Although adjustment disorder is common, there is a dearth of research on its physical health consequences. Earlier studies, biological mechanisms and stress-related behaviors suggest that cancer may be a potential sequelae of adjustment disorder. This study examined the association between adjustment disorder and type-specific cancer incidence in a nationwide cohort. METHODS: Data were obtained from the comprehensive nationwide medical and administrative registries of Denmark. We calculated the incidence of type-specific cancers from 1995 to 2013 in patients with a prior adjustment disorder diagnosis (n = 58,712), and compared it with the incidence in the general population by calculating standardized incidence ratios (SIRs) with accompanying 95% confidence intervals (CIs). SIRs were adjusted using semi-Bayes shrinkage. RESULTS: The SIR for any type of cancer was 1.0 (95% CI: 0.99, 1.1). Adjustment disorder was associated with a 10% lower rate of immune-related cancers (SIR = 0.9, 95% CI: 0.84, 0.97) and with a 20% higher rate of smoking- and alcohol-related cancers (SIR = 1.2, 95% CI: 1.1, 1.3). We found null associations for hematological (SIR = 1.1, 95% CI: 0.89, 1.3) and hormone-related (SIR = 0.98, 95% CI: 0.91, 1.1) malignancies. After semi-Bayes adjustment, type-specific cancer SIRs indicated no association between adjustment disorder and cancer incidence. CONCLUSIONS: This study provides persuasive evidence for a null association between adjustment disorder and type-specific cancer incidence in a nationwide study cohort.

Cancer Incidence in Patients With Acromegaly: A Cohort Study and Meta-Analysis of the Literature.

Context: Acromegaly has been associated with increased risk of cancer morbidity and mortality, but research findings remain conflicting and population-based data are scarce. We therefore examined whether patients with acromegaly are at higher risk of cancer. Design: A nationwide cohort study (1978 to 2010) including 529 acromegaly cases was performed. Incident cancer diagnoses and mortality were compared with national rates estimating standardized incidence ratios (SIRs). A meta-analysis of cancer SIRs from 23 studies (including the present one) was performed. Results: The cohort study identified 81 cases of cancer after exclusion of cases diagnosed within the first year [SIR 1.1; 95% confidence interval (CI), 0.9 to 1.4]. SIRs were 1.4 (95% CI, 0.7 to 2.6) for colorectal cancer, 1.1 (95% CI, 0.5 to 2.1) for breast cancer, and 1.4 (95% CI, 0.6 to 2.6) for prostate cancer. Whereas overall mortality was elevated in acromegaly (SIR 1.3; 95% CI, 1.1 to 1.6), cancer-specific mortality was not. The meta-analysis yielded an SIR of overall cancer of 1.5 (95% CI, 1.2 to 1.8). SIRs were elevated for colorectal cancer, 2.6 (95% CI, 1.7 to 4.0); thyroid cancer, 9.2 (95% CI, 4.2 to 19.9); breast cancer, 1.6 (1.1 to 2.3); gastric cancer, 2.0 (95% CI, 1.4 to 2.9); and urinary tract cancer, 1.5 (95% CI, 1.0 to 2.3). In general, cancer SIR was higher in single-center studies and in studies with <10 cancer cases. Conclusions: Cancer incidence rates were slightly elevated in patients with acromegaly in our study, and this finding was supported by the meta-analysis of 23 studies, although it also suggested the presence of selection bias in some earlier studies.

Diagnosis of hyponatremia and increased risk of a subsequent cancer diagnosis: results from a nationwide population-based cohort study.

BACKGROUND: Hyponatremia has recently been associated with subsequent cancer risk. This population-based nationwide study assessed whether the diagnosis of hyponatremia can predict a cancer diagnosis within most common cancers. MATERIAL AND METHODS: Using Danish medical registries, we identified 16,220 patients with a first-time diagnosis of hyponatremia, without a cancer diagnosis, from January 2006 through November 2013. We quantified the relative risk of a subsequent cancer diagnosis by standardized incidence ratios (SIRs), comparing observed cancer incidence among patients diagnosed with hyponatremia to that expected, based on national cancer incidence during that period. RESULTS: During 40,207 person-years of follow-up, we observed 1546 cancer diagnoses compared to 956 expected (SIR: 1.62; 95% confidence interval (CI), 1.54-1.70). The increase in risk of a cancer diagnosis following a hyponatremia diagnosis was most pronounced within 0-6 months of follow-up (SIR 4.16; 95% CI, 3.85-4.48) and in the younger age group; 0-29 years (SIR 8.71; 95% CI, 2.82-20.28), 30-49 years (SIR 3.16; 95% CI, 2.26-4.31), 50-69 years (SIR 2.29; 95% CI, 2.10-2.48) and 70 + years (SIR 1.35; 95% CI, 1.27-1.44). Within six months after a hyponatremia diagnosis, the SIRs increased 10-fold for cancers of the lung (SIR 17.14; 95% CI, 15.15-19.32), brain (SIR 13.52; 95% CI, 8.90-19.66) and liver (SIR 13.26; 95% CI, 7.57-21.53) and increased 5 to 10-fold for cancers of the pancreas (SIR 8.25; 95% CI, 5.72-11.53), esophagus (SIR 6.59; 95% CI, 3.15-12.12), kidney (SIR 6.36; 95% CI, 3.39-10.88), pharynx (SIR 6.15; 95% CI, 1.27-17.97) and non-Hodgkin lymphoma (SIR 6.10; 95% CI, 4.17-8.61). The rate increased across virtually all types of cancers, except melanoma and basal cell carcinomas. CONCLUSIONS: A diagnosis of hyponatremia may be a marker of occult neoplasms, especially cancers of the lung, brain, liver, pancreas, esophagus, kidney, pharynx and non-Hodgkin lymphoma. Hyponatremia may aid in early detection of cancer.

Pericarditis as a Marker of Occult Cancer and a Prognostic Factor for Cancer Mortality.

BACKGROUND: Pericarditis may be a serious complication of malignancy. Its significance as a first symptom of occult cancer and as a prognostic factor for cancer survival is unknown. METHODS: Using Danish medical databases, we conducted a nationwide cohort study of all patients with a first-time diagnosis of pericarditis during 1994 to 2013. We excluded patients with previous cancer and followed up the remaining patients for subsequent cancer diagnosis until November 30, 2013. We calculated risks and standardized incidence ratios of cancer for patients with pericarditis compared with the general population. We assessed whether pericarditis predicts cancer survival by the Kaplan-Meier method and Cox regression using a matched comparison cohort of cancer patients without pericarditis. RESULTS: Among 13 759 patients with acute pericarditis, 1550 subsequently were diagnosed with cancer during follow-up. The overall cancer standardized incidence ratio was 1.5 (95% confidence interval [CI], 1.4-1.5), driven predominantly by increased rates of lung, kidney, and bladder cancer, lymphoma, leukemia, and unspecified metastatic cancer. The <3-month cancer risk among patients with pericarditis was 2.7%, and the standardized incidence ratio was 12.4 (95% CI, 11.2-13.7). The 3- to <12-month standardized incidence ratio of cancer was 1.5 (95% CI, 1.2-1.7), subsequently decreasing to 1.1 (95% CI, 1.0-1.2). Three-month survival after the cancer diagnosis was 80% and 86% among those with and without pericarditis, respectively, and the hazard ratio was 1.5 (95% CI, 1.3-1.8). One-year survival was 65% and 70%, respectively, corresponding to a 3- to <12-month hazard ratio of 1.3 (95% CI, 1.1-1.5). CONCLUSIONS: Pericarditis may be a marker of occult cancer and augurs increased mortality after a cancer diagnosis.

Elevated plasma vitamin B12 levels and risk of venous thromboembolism among cancer patients: A population-based cohort study.

INTRODUCTION: Both venous thromboembolism (VTE) and high plasma vitamin B12 levels (cobalamin, Cbl) are markers of occult cancer and aggressive cancer with a poor prognosis. In this population-based cohort study, we assessed VTE risk among cancer patients with high plasma Cbl levels. MATERIALS AND METHODS: We used Danish health registries to identify a Cb1 cohort of 25,310 cancer patients with a plasma Cbl measurement prior to cancer diagnosis. The cohort was subdivided according to Cbl levels (pmol/L): 200-600 (population reference range), 601-800 and >800. All VTE events were considered provoked and categorised as either cancer-associated if no other provoking factors were present before VTE or provoked by other risk factors (surgery, trauma, or pregnancy). We calculated cumulative incidence proportions and adjusted hazard ratios computed from Cox regression analysis (reference: plasma Cbl of 200-600pmol/L) for the risk of VTE before and after the cancer diagnosis date (index date). RESULTS: The risk of cancer-associated VTE 30days after index date increased with higher Cbl levels. The cumulative incidence (95% CI) by Cbl levels was: 200-600pmol/L: 0.24 (0.18-0.31); 601-800pmol/L: 0.63 (0.34-1.09); >800pmol/L: 0.86 (0.49-1.40). Adjusted hazard ratios (95% CI) were: 601-800 vs. 200-600: 2.55 (1.32-4.92); >800 vs. 200-600: 2.36 (1.19-4.71). We found similar results for VTE provoked by other risk factors and for VTE occurring before index date, but scarcity of events produced uncertain risk estimates. CONCLUSION: We demonstrated an association between high plasma Cbl levels and risk of VTE in cancer patients. Any clinical implications warrant further study.