Trends in Staging, Treatment, and Survival in Colorectal Cancer Between 1990 and 2014 in the Rotterdam Study.

BACKGROUND: This study aims to assess trends in patient-related factors and treatment strategies in Dutch colorectal cancer (CRC) patients and their effect on survival. METHODS: Data were obtained from the Rotterdam study, an ongoing population-based study of individuals aged ≥45 years. Between 1990 and 2014, incident, pathology-confirmed CRC cases were divided into two groups based on date of diagnosis (either before or after January 1, 2003). Patient characteristics, initial treatment, and date of mortality were collected. Analyses were performed using Kaplan-Meier and Cox proportional hazard models. RESULTS: Of 14,928 individuals, 272 developed colon cancer and 124 rectal cancer. Median follow-up was 13.2 years. Patients diagnosed after January 1, 2003 were treated chemotherapeutically more often than those diagnosed prior to this date in colon cancer (28.6% vs. 9.1%, p = 0.02) and treated more often with chemotherapy (38.6% vs. 12.3%, p = 0.02) and radiotherapy (41.3% vs. 10.2%, p = 0.001) in rectal cancer. Overall survival, adjusted for patient, tumor characteristics, and treatment, improved in rectal cancer (HR, 0.31; 95% CI, 0.13-0.74) but remained stable in colon cancer (HR, 1.28; 95% CI, 0.84-1.95). CONCLUSION: Chemotherapeutic agents and radiotherapy are increasingly used in CRC patients. Survival in rectal cancer improved, whereas in colon cancer this was not observed.

The systemic immune-inflammation index is associated with an increased risk of incident cancer-A population-based cohort study.

Several studies found that the systemic immune-inflammation index (SII) is a prognostic factor for mortality in patients with solid tumors. It is unknown whether an increased SII in generally healthy individuals reflects a risk for developing cancer. Our objective was to investigate the association between the SII and incident cancers in a prospective cohort study. Data were obtained from the Rotterdam Study; a population-based study of individuals aged ≥45 years, between 2002 and 2013. The SII at baseline was calculated from absolute blood counts. The association between the SII and the risk of any solid incident cancer during follow-up was assessed using Cox proportional hazard models. Individuals with a prior cancer diagnosis were excluded. Data of 8,024 individuals were included in the analyses. The mean age at baseline was 65.6 years (SD 10.5 years) and the majority were women. During a maximum follow-up period of 10.7 years, 733 individuals were diagnosed with cancer. A higher SII at baseline was associated with a 30% higher risk of developing a solid cancer (HR of 1.30 [95% CI; 1.11-1.53]), after adjustment for age, sex, socioeconomic status, smoking, BMI and type 2 diabetes. The absolute cumulative 10-year cancer risk increased from 9.7% in the lowest quartile of SII to 14.7% in the highest quartile (p-value = 0.009). The risk of developing cancer was persistent over time and increased for individuals with the longest follow-up. In conclusion, a high SII is a strong and independent risk indicator for developing a solid cancer.

Search for Early Pancreatic Cancer Blood Biomarkers in Five European Prospective Population Biobanks Using Metabolomics.

Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between 1 month and 17 years after sampling (N = 356) and age- and sex-matched controls (N = 887) were collected from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian Biobank, Rotterdam Study). We applied proton nuclear magnetic resonance-based metabolomics on the Nightingale platform. Logistic regression identified two interesting hits: glutamine (P = 0.011) and histidine (P = 0.012), with Westfall-Young family-wise error rate adjusted P values of 0.43 for both. Stratification in quintiles showed a 1.5-fold elevated risk for the lowest 20% of glutamine and a 2.2-fold increased risk for the lowest 20% of histidine. Stratification by time to diagnosis suggested glutamine to be involved in an earlier process (2 to 5 years before diagnosis), and histidine in a process closer to the actual onset (<2 years). Our data did not support the branched-chain amino acids identified earlier in several US cohorts as potential biomarkers for pancreatic cancer. Thus, although we identified glutamine and histidine as potential biomarkers of biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers.

Balance between innate versus adaptive immune system and the risk of dementia: a population-based cohort study.

BACKGROUND: Immunity has been suggested to be important in the pathogenesis of dementia. However, the contribution of innate versus adaptive immunity in the development of dementia is not clear. In this study, we aimed to investigate (1) the association between components of innate immunity (granulocytes and platelets) and adaptive immunity (lymphocytes) with risk of dementia and (2) the association between their derived ratios (granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII]), reflecting the balance between innate and adaptive immunity, with risk of dementia. METHODS: Blood cell counts were measured repeatedly between 2002 and 2015 in dementia-free participants of the prospective population-based Rotterdam Study. Participants were followed-up for dementia until 1 January 2016. Joint models were used to determine the association between granulocyte, platelets, and lymphocyte counts, and their derived ratios with risk of dementia. RESULTS: Of the 8313 participants (mean [standard deviation] age 61.1 [7.4] years, 56.9% women), 664 (8.0%) developed dementia during a median follow-up of 8.6 years. Doubling of granulocyte and platelet counts tended to be associated with an increased risk of dementia (HR [95%CI] 1.22 [0.89-1.67] and 1.45 [1.07-1.95], respectively). Doubling of the derived ratios GLR, PLR, and SII were all associated with an increased dementia risk (HR [95%CI] 1.26 [1.03-1.53], 1.27 [1.05-1.53], and 1.15 [0.98-1.34], respectively). CONCLUSIONS: GLR, PLR, and SII are associated with an increased risk of dementia in the general population. This supports the role of an imbalance in the immune system towards innate immunity in the pathogenesis of dementia.

The neutrophil-to-lymphocyte ratio is associated with mortality in the general population: The Rotterdam Study.

Inflammation is a risk factor for morbidity and mortality in the elderly. The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that integrates the information of the leukocyte differentials into one variable. We aimed to assess whether the NLR is a risk indicator for overall and cause-specific mortality in the general population. We analyzed data (2002-2014) from the Rotterdam Study, a long-standing, population-based, prospective cohort study in a community-dwelling ageing population. The association between the NLR and time to all-cause mortality was assessed with Cox proportional hazard models. We additionally assessed cardiovascular, cancer and other mortality. The multivariable analyses were adjusted for age, gender, socio-economic status (SES), smoking status, body mass index, type 2 diabetes, and history of cancer and cardiovascular disease (CVD). Data of 8715 individuals were included. The mean age was 65.9 years (SD 10.5) and the majority were women (57.1%). The NLR was higher in men, higher age categories, smokers and among individuals with lower SES, prevalent diabetes, or a history of cancer or CVD. During the 11.7 years follow-up period, 1641 individuals died. Survival among individuals in the 3rd, 4th, and 5th quintile of the NLR was significantly poorer than that of those in the 1st quintile (P < 0.001). In the multivariable analysis, NLR levels were independently and significantly associated with an increased risk of all-cause mortality (HR 1.64; 95% CI 1.44-1.86), cardiovascular mortality (HR 1.92; 95% CI 1.49-2.48), and other mortality (HR 1.86; 95% CI 1.54-2.24). No significant association was found for cancer mortality (HR 1.20; 95% CI 0.95-1.51). The NLR is a strong and independent risk indicator for mortality in the elderly population. Its clinical value needs to be established in further studies.

Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study: a population-based prospective cohort study.

Novel prognostic inflammatory markers of cancer survival and cardiovascular disease are; the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammation index (SII). As normal values for these markers are unknown, our objective was to obtain reference values in the general population. We obtained data from a population-based prospective cohort study of individuals aged 45 years and over between 2002 and 2014. Absolute blood counts were used to calculate the NLR, PLR and SII. All inflammatory indices followed a log-normal distribution. We calculated the mean and 95% reference intervals in an unselected population. Furthermore we studied whether the inflammatory markers differed between age categories and gender. In total 8,711 participants (57.1% female; mean age 65.9 years, standard deviation 10.5 years) were included. Mean values and corresponding 95% reference intervals for the NLR were: 1.76 (0.83-3.92), for PLR: 120 (61-239) and for SII: 459 (189-1168). The inflammatory markers increased with age. The PLR and SII were higher in females, whilst the NLR was higher in males. In conclusion, we provided reference values for new inflammatory markers. All increase with age and vary with gender. This provides context that allows for proper interpretation of their potential value in future clinical practice and research.

Consequences of Referral Time and Volume Doubling Time in Inoperable Patients With Early Stage Lung Cancer.

BACKGROUND: Inoperable patients with early stage lung cancer are referred late. The purpose was to calculate the referral time and the volume doubling time (VDT), and to investigate its consequence with regard to staging and survival in 117 inoperable patients with early stage lung cancer treated with stereotactic body radiotherapy. MATERIALS AND METHODS: Tumor VDT was calculated using the modified Schwartz formula of exponential growth model and was on the basis of volumes measured on initial diagnostic computed tomography (CT) scans and the planning CT scan. VDT was defined as fast (<100 days), moderate (100-249 days), slow (250-399 days), and no growth (≥400 days). The referral time is the time between the diagnostic CT scan and the radiotherapy planning CT scan. RESULTS: The median referral time was 86 days. The VDT was fast in 53 patients [45%] of tumors. No significant difference in VDT was found between different tumor or patient characteristics. Patients with T1 tumors that progressed to T2 had a significant worse median survival (P = .01). The overall survival at 5 years according to VDT was 21% for fast-growing tumors, 19% for moderate growth, 31% for slow, and 46% for no growth. CONCLUSION: The median referral time was almost 3 months. VDT was considered as fast in almost half of tumors examined. This resulted in significant growth and upstaging in 35% of the tumors, with a significant worse survival if T1 tumors progressed to T2 tumors. Therefore, medically inoperable patients should also be offered a fast workup and referral.

[Appendectomy followed by a pancreaticoduodenectomy: a solid pseudopapillary neoplasm of the pancreas]. / Een appendectomie gevolgd door een pancreaticoduodenectomie: solide pseudopapillair neoplasma van het pancreas.

BACKGROUND: Increasing usage and improved quality of imaging has increased the probability of incidentalomas which raises the question of how to deal with them. The following case illustrates the incidental finding of a tumour on a CT-scan. CASE DESCRIPTION: A 23-year-old woman presented at our emergency department with acute abdominal pain. During the workup we found that in addition to an acute appendicitis, she had a tumour in the pancreas. Cytology initially indicated pancreatic carcinoma, however, further analysis showed a solid pseudopapillary neoplasm of the pancreas. The patient underwent a pylorus-preserving pancreaticoduodenectomy. CONCLUSION: A solid pseudopapillary neoplasm is a relatively rare disorder of the pancreas which is mostly seen in young females. It is a benign disorder carrying a small risk of malignant transformation. A pylorus-preserving pancreaticoduodenectomy is the treatment of choice for this benign tumour of the head of pancreas.