Evolution of Diagnoses, Survival, and Costs of Oncological Medical Treatment for Non-Small-Cell Lung Cancer over 20 Years in Osona, Catalonia.

Non-small-cell lung cancer (NSCLC) has experienced several diagnostic and therapeutic changes over the past two decades. However, there are few studies conducted with real-world data regarding the evolution of the cost of these new drugs and the corresponding changes in the survival of these patients. We collected data on patients diagnosed with NSCLC from the tumor registry of the University Hospital of Vic from 2002 to 2021. We analyzed the epidemiological and pathological characteristics of these patients, the diverse oncological treatments administered, and the survival outcomes extending at least 18 months post-diagnosis. We also collected data on pharmacological costs, aligning them with the treatments received by each patient to determine the cost associated with individualized treatments. Our study included 905 patients diagnosed with NSCLC. We observed a dynamic shift in histopathological subtypes from squamous carcinoma in the initial years to adenocarcinoma. Regarding the treatment approach, the use of chemotherapy declined over time, replaced by immunotherapy, while molecular therapy showed relative stability. An increase in survival at 18 months after diagnosis was observed in patients with advanced stages over the most recent years of this study, along with the advent of immunotherapy. Mean treatment costs per patient ranged from EUR 1413.16 to EUR 22,029.87 and reached a peak of EUR 48,283.80 in 2017 after the advent of immunotherapy. This retrospective study, based on real-world data, documents the evolution of pathological characteristics, survival rates, and medical treatment costs for NSCLC over the last two decades. After the introduction of immunotherapy, patients in advanced stages showed an improvement in survival at 18 months, coupled with an increase in treatment costs.

Yolk sac tumor differentiation in urothelial carcinoma of the urinary bladder: a case report and differential diagnosis.

BACKGROUND: Yolk sac tumor (YST) is a germ cell neoplasm that arises predominantly in the gonads, but can also derive from somatic neoplasms in extragonadal locations. These latter cases have been documented in several organs, although reports from the urinary tract are limited. To our knowledge, this is the first report of a bladder urothelial carcinoma with a predominant component of YST differentiation. CASE PRESENTATION: We present a unique case of a 76-year-old man with a recurrent urinary bladder tumor, initially interpreted as a high grade urothelial carcinoma with glandular differentiation. In the recurrent tumor, diverse histological patterns were identified, including glandular, hepatoid and sarcomatoid. This tumor showed positivity for AFP, GLP3 and SALL4, and negativity for CK7 and EMA. Fluorescent in situ hybridization study showed a polysomic pattern of chromosome 12. All these findings led to the final diagnosis of a YST derived from urothelial carcinoma. CONCLUSIONS: YST differentiation should be considered in the differential diagnosis of a high grade urothelial carcinoma, particularly when glandular and other unusual patterns are observed.

Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) µg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

BACKGROUND: Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited. OBJECTIVE: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase-control study. METHODS: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis. RESULTS: Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate. CONCLUSIONS: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status. CITATION: Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.

Colorectal cancer risk and nitrate exposure through drinking water and diet.

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. A case-control study in Spain and Italy during 2008-2013 was conducted. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects' residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

Nitrate in drinking water and bladder cancer risk in Spain.

BACKGROUND: Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables. METHODS: We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview. RESULTS: Average residential levels ranged from 2.1mg/L to 12.0mg/L among regions. Adjusted OR (95%CI) for average residential levels relative to ≤ 5 mg/L were 1.2 (0.7-2.0) for >5-10mg/L and 1.1 (0.6-1.9) for >10mg/L. The OR for subjects with longest exposure duration (>20 years) to highest levels (>9.5mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for >8 vs. ≤ 4 mg/day. Adjustment for several covariables showed similar results to crude analyses. CONCLUSION: Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed.

Factores de riesgo para enfermedad diarreica aguda con deshidratación grave en pacientes de 2 meses a 5 años / Risk factors associated with diarrheal and severe dehydration in children between 2 months and 5 years old

Con el Objetivo de identificar los factores de riesgo asociados a enfermedad diarreica aguda (EDA) con deshidratación grave en los pacientes atendidos en el Hospital del Niño "Dr. Ovidio Aliaga Uria", se realizó un estudio de casos y controles incidentes. En niños de 2 meses a 5 años con enfermedad diarreica aguda: 60 casos (EDA con deshidratación grave) y 120 controles (EDA sin deshidratación o deshidratación leve), evaluándose los siguientes factores: edad, prematurez, estado nutricional, características clínicas del episodio diarreico actual, uso de sales de rehidratación oral y antibióticos, atención médica previa, edad y nivel educativo de la madre, duración de la lactancia materna, hacinamiento, eliminación de excretas e inmunizaciones. En el análisis multivariado se identificaron los siguientes factores de riesgo: Edad menor a 18 meses, desnutrición, duración de la enfermedad mayor a tres días, frecuencia de deposiciones mayor a 5/día, más de 3 vómitos/ día, uso de medicina natural, falta de alcantarillado y hacinamiento. La vacunación completa contra rotavirus resulto factor protector frente a la diarrea con deshidratación. El estudio concuerda con estudios similares, poniendo en relevancia los factores de riesgo frecuentes en nuestra población que deben tomarse en cuenta al momento de atender a pacientes con cuadros enterales con riesgo de deshidratación grave.

To identify risk factors associated with diarrheal and severe dehydration in children between 2 and 5 years old, was performed a study of incident cases and controls. In multivariate analysis the following risk factors were identified: age less than 18 months, malnutrition, more than 3 days sickness, increased stool frequency, frequent vomiting, use of natural medicine, lack of sewerage and overcrowding. The full rotavirus vaccination resulted protective factor against diarrhea with dehydration. The study is consistent with similar studies, identify common risk factors in our population should be considered in children with diarrhea.

Nitrate and trace elements in municipal and bottled water in Spain / Nitrato y elementos traza en agua embotellada y municipal en España

Objectives: To describe levels of nitrate and trace elements in drinking water from the study areas of a multicase-control study of cancer in Spain (MCC-Spain). Methods: A total of 227 tap water samples were randomly collected from 67 municipalities in 11 provinces and the nine most frequently consumed bottled water brands were sampled to measure levels of nitrate, arsenic, nickel, chromium, cadmium, lead, selenium and zinc. Results: The median nitrate level was 4.2mg/l (range<1-29.0), with similar levels in rural and urban municipalities (p=0.86). Trace elements were unquantifiable in 94% of tap water samples. Differences between areas were significant for nitrate (p<0.001) and arsenic (p=0.03). Only nitrate was quantifiable in bottled water (range 2.3-15.6mg/l). Conclusions: Nitrate levels in municipal water differed between regions and were below the regulatory limit in all samples, including bottled water. Trace element levels were low and mainly unquantifiable in tap and bottled water (AU)

Objetivos: Determinar las concentraciones de nitrato y de elementos traza en el agua de consumo de las áreas del estudio Multicaso-Control de Cáncer en España (MCC-Spain). Métodos: Se tomaron al azar 227 muestras de agua municipal en 67 municipios de 11 provincias, y 9 muestras de las aguas embotelladas más consumidas, para cuantificar la cantidad presente de nitrato, arsénico, níquel, cromo, cadmio, plomo y zinc. Resultados: La mediana de las cifras de nitrato fue 4,2mg/l (rango<1-29,0), con similares resultados en municipios urbanos y rurales (p=0,86). Los elementos traza fueron incuantificables en el 94% de las muestras de agua municipal. Se observaron diferencias entre áreas para nitrato (p<0,001) y arsénico (p=0,03). Solo el nitrato fue cuantificable en el agua embotellada (rango 2,3-15,6mg/l). Conclusiones: La cantidad de nitrato en el agua municipal difiere entre regiones y es menor que el límite regulatorio en todas las muestras. Los elementos traza son mayormente incuantificables tanto en el agua municipal como en la embotellada (AU)

Swimming pool attendance, respiratory symptoms and infections in the first year of life.

UNLABELLED: We evaluated the relationship between indoor and outdoor swimming pool attendance and respiratory symptoms and infections during the first year of life. A population-based mother-child cohort study was conducted in four Spanish areas (INMA project). Study subjects were recruited at pregnancy, followed to delivery and 14 months after birth. Information on swimming pool attendance and health manifestations during the first year of life was collected at 14 months: low respiratory tract infection (LRTI), persistent cough, wheezing, atopic eczema and otitis. Odds ratios and 95 % confidence interval (OR 95 %CI) were calculated by logistic regression adjusting for confounders. Among the 2,205 babies included, 37 % reported having LRTI, 37 % wheezing, 16 % persistent cough, 22 % atopic eczema, 33 % otitis and 50 % attended swimming pools during the first year of life. Around 40 % went to outdoor pools in summer with a median cumulative duration of 7.5 h/year, and 20 % attended indoor pools with a median cumulative duration of 18 h/year. Pool attendance differed by area, season of birth and sociodemographic characteristics, and was not associated with LRTI, wheezing, persistent cough, atopic eczema or otitis. Adjusted OR of wheezing and LRTI were, respectively, 1.06 (95 %CI, 0.88-1.28) and 1.09 (0.90-1.31) for babies attending vs. babies not attending pools. Stratification by type of swimming pool, cumulative duration or parental atopy did not modify the results. CONCLUSION: No association was detected between pool attendance and LRTI, wheezing, persistent cough, atopic eczema or otitis during the first year of life in Spain.

Nitrate and trace elements in municipal and bottled water in Spain.

OBJECTIVES: To describe levels of nitrate and trace elements in drinking water from the study areas of a multicase-control study of cancer in Spain (MCC-Spain). METHODS: A total of 227 tap water samples were randomly collected from 67 municipalities in 11 provinces and the nine most frequently consumed bottled water brands were sampled to measure levels of nitrate, arsenic, nickel, chromium, cadmium, lead, selenium and zinc. RESULTS: The median nitrate level was 4.2mg/l (range<1-29.0), with similar levels in rural and urban municipalities (p=0.86). Trace elements were unquantifiable in 94% of tap water samples. Differences between areas were significant for nitrate (p<0.001) and arsenic (p=0.03). Only nitrate was quantifiable in bottled water (range 2.3-15.6mg/l). CONCLUSIONS: Nitrate levels in municipal water differed between regions and were below the regulatory limit in all samples, including bottled water. Trace element levels were low and mainly unquantifiable in tap and bottled water.