Use of the Minimum Basic Data Set as a tool for the epidemiological surveillance of mesothelioma.

BACKGROUND: Mesothelioma is a very aggressive tumor that appears after several decades of asbestos exposure. The Minimum Basic Data Set (MBDS) has been validated for the incidence of mesothelioma in Italy, but not in Spain. The objectives of this investigation are: to estimate the prevalence, incidence and mortality of mesothelioma in the Community of Madrid (CM); to evaluate the distribution of this risk within the territory; and to explore validity of the MBDS in the epidemiological surveillance of mesothelioma. METHODS: Prevalence, incidence and mortality mesothelioma rates were calculated for the CM from data of the MBDS (2016 and 2017), and mortality data of the Spanish National Statistics Institute (INE) for the same period. The geographical distribution of cases and deaths, and its correlation at municipal level was studied. Statistical analysis with R and Excel tools was carried out. RESULTS: The incidence of mesothelioma in the CM was higher than in previous years. Mortality estimated by the MBDS and calculated using INE data for 2016 were similar in the CM. The correlation between the geographical patterns of risk of mesothelioma obtained from the two sources was high (r = 0.86). The aggregation of cases continues in municipalities in the south, detecting the maximum risk in Aranjuez. CONCLUSION: The MBDS and INE are good resources for monitoring the risk of mesothelioma. New studies that investigate the aggregation of cases in Aranjuez are required.

Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.

Oligomers of ß-amyloid protein (Aß1-42) induce the activation of cyclooxygenase-2 in astrocytes via an interaction with interleukin-1ß, tumour necrosis factor-α, and a nuclear factor κ-B mechanism in the rat brain.

Despite growing evidence indicating the effects of cytokines, including interleukin-1beta (IL-1ß) and tumour necrosis factor-α (TNFα), and the enzyme cyclooxygenase-2 (COX-2) in Alzheimer's diseases, little is known about the signalling mechanisms that mediate its activation in response to beta-amyloid protein (Aß). The aim of this study was first to investigate whether Aß1-42 peptide induced the up-regulation of COX-2. We then examined the expression of COX-2 and cytokines, such as IL-1ß and TNFα, in reactive astrocytes. Finally, we analyzed the role of nuclear factor kappa-B (NF-κB) as a signalling pathway in early stages of Aß-toxicity. In Wistar rats anaesthetised with equitesine, a single microinjection of Aß1-42 oligomers was made in the left retrosplenial cortex. Control animals were injected with Aß42-1 peptide into the corresponding region of the cerebral cortex. By COX-2 immunoblotting, we detected two immunopositive protein bands, at 70 and 50 kDa molecular mass. In the Aß1-42-injected animals the 50 kDa fragment showed a significant increase at 3 and 14 days, as compared with that seen in control animals. The 70 kDa fragment showed a maximal increase at 14 days. In the Aß1-42-injected animals immunoblot staining of NF-κB detected an active protein band at 50 kDa molecular mass, showing a maximal increase at the 72 h time point. Confocal analysis revealed that COX-2 protein co-localized with Aß-IR material at the injection site and in endothelial blood vessels, increasing at 72 h. In the Aß oligomer-treated animals, COX-2, IL-1ß, and TNFα proteins were expressed in reactive astrocytes surrounding the injection site and blood vessels at early stages of Aß toxicity. Double-labelling immunofluorescence studies also revealed that GFAP and COX-2 proteins co-localized with NF-κB-positive material at early time-points. In conclusion, our results suggest that in reactive astrocytes and in COX-2 positive cells NF-κB may mediate pro-, and/or inflammatory gene expression and that, develop strategies that target the GFAP/NF-κB and COX-2/NF-κB pathways might contribute to reducing Aß-induced toxicity.

Helicobacter pylori cagA and vacA genotypes as predictors of progression of gastric preneoplastic lesions: a long-term follow-up in a high-risk area in Spain.

OBJECTIVES: There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. METHODS: This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffin-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter- and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. RESULTS: The mean age of patients was 48.5 years (45% males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA, vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR)=2.28, 95% confidence interval (CI) 1.13-4.58; OR=2.90, 95% CI 1.38-6.13; and OR=3.38, 95% CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1/m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95% CI 1.71-13.5) in relation to those infected with cagA-negative/vacA s2/m2 strains. CONCLUSIONS: H. pylori genotyping may be useful for the identification of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.

Aspiration cytology of 147 adnexal cysts with histologic correlation.

OBJECTIVE: To assess the usefulness of cytology in the diagnosis of 147 histologically established adnexal cysts. STUDY DESIGN: Retrospective, macro-microscopic study based on fluid aspirated from 132 ovarian and 15 extraovarian cysts and projected as a cytohistologic correlation. RESULTS: Typical macroscopic features were identified in 76% of endometriotic cysts, in 53% of mucinous neoplasms and in 67% of dermoid cysts. Cytology helped to identify 67% of nonneoplastic and 56% of neoplastic cysts. The lowest diagnostic sensitivities were observed in functional cysts and benign serous neoplasms (50%), while the highest were shown by endometriotic cysts (76%) and malignant epithelial neoplasms (71%). Inadequate samples were obtained from all types of cysts, even malignant ones (two mucinous cystadenocarcinomas). Diagnostic cytology was useless in extraovarian cysts (33% sensitivity). An adult granulosa cell tumor was erroneously diagnosed as a follicular cyst by cytologic examination. CONCLUSION: Examination of the cyst fluids obtained by aspiration demonstrated low sensitivity, with 43% of inadequate samples obtained from all types of cysts. Malignant cystic neoplasms may be overlooked in inadequate samples. Our study also revealed that specificity in this type of analysis is high in inadequate samples, provided that the technique is carried out correctly.

Consumption of wine stored in leather wine bottles and incidence of gastric cancer.

The authors conducted a survey among participants of a large-scale case-control study to evaluate a possible association between consumption of wine in leather bottles and incidence of gastric cancer. There were 59 cases and 53 controls in the study. The results suggest that some of the components of the complex mixture (i.e., tar) used in the proofing of leather wine bottles might dissolve in the wine and participate in the etiology of gastric cancer. Nevertheless, the results should be confirmed in an independent study.

Sex as a prognostic factor in gastric cancer.

The aim of this study was to assess whether survival of gastric cancer patients differed between males and females. Although it is well known that the incidence of gastric cancer is higher for men than for women, the existence of a sex-specific prognosis has seldom been addressed. Studies based on population registries have not assessed the role of stage and histology. Cases of histologically confirmed gastric carcinoma were obtained from three Spanish hospitals in Soria (n = 405), Barcelona (n = 249) and Mataró (n = 197). Differences in possible confounders were tested between men and women and survival analyses were performed separately by hospital. Cox's proportional hazards models were used to account for age, tumour stage, histology and tumour sub-location. Only in Mataró was a significant difference in the stage distribution observed between women and men, with a lower proportion of local stage tumours among women (P = 0.047). No statistically significant differences of histological type between men and women were observed in any of the centres. After adjusting for tumour stage and age, women were observed to have significantly better survival in Barcelona (female to male hazard ratio (HR) = 0.578, P < 0.001); this effect was marginal in Soria (HR = 0.788, P = 0.092) and non-significant in Matar-o (HR = 0.895, P = 0.54). Age-adjusted hazard ratios were calculated within each tumour stage. For Barcelona, the effect of better prognosis among women was most marked at local stage (HR = 0.320, P = 0.013), and in Soria at the regional stage (HR = 0.426, P = 0.002). Although in Mataró all HRs were below unity, none were statistically significant. Little effect was observed at the disseminated stage. The other covariables exerted no influence. Women appear to have a better prognosis than men, and the difference could be tumour stage dependent. Confirmation of these findings would give a valuable insight into gastric cancer growth and ultimately be of use in planning treatment.

[Eosinophilic cholecystitis associated with rupture of hepatic hydatid cyst of the bile ducts]. / Colecistitis eosinofílica asociada a ruptura de un quiste hidatídico hepático en vías biliares.

Eosinophilic cholecystitis is a rare finding characterized by an inflammatory infiltrate composed primarily of eosinophils. We report a case of eosinophilic cholecystitis associated with hepatic hydatic cyst ruptured into the biliary tract. The release of hydatid cyst content into the biliary tract may have induced a hypersensitivity reaction with numerous eosinophils in the gallbladder wall.

[Blue nevus of the prostate]. / Nevus azul de la próstata.

The presence of melanin in the prostatic gland's stroma is a histopathological finding of extreme rarity. It receives the name of blue nevus as a result of its similitude to the skin's blue nevus. The paper describes the finding of melanin stores in the fibromuscular stroma of a patient's prostate and reviews the theories on its source.

[Incidence and mortality of laryngeal neoplasms. Soria, 1950-1989]. / Incidencia y mortalidad neoplásica laríngea. Soria, 1950-1989.

Age-adjusted mortality and incidence rates for larynx cancer were calculated in Soria (urban and rural areas), for the 1950-89 and 1981-89 periods respectively. Both mortality and incidence rates were higher in urban area (p less than 0.01), and in males (p less than 0.01). There has been no increase in the mortality trend for the 1950-89 period. Age-adjusted incidence rates for men in Soria are higher respect to those reported in other countries. Soria and Murcia rates are the lowest in Spain larynx cancer records, being Asturias rates the highest in the world (20.6 per 100,000 population).

[Mortality trends in gynecologic tumors in Soria. 1950-1985]. / Tendencias de mortalidad por tumores ginecológicos en Soria. 1950-1985.

We have carried out in the province of Soria neoplastic mortality tendency curves for tumors in the breast, uterus and ovaries, on the basis of their adjusted rates of mortality during four periods: three decades (1950-59/60-69/70-79) and one six-year period (1980-85). We have observed an increased risk of mortality due to breast tumors in women, which is statistically significant (p less than 0.01) in the global provincial figure, which has gone from an adjusted rate of 6.08 deaths per 10(5) women in 1950-59 to 14.25 in the years 1980-85. We have also detected an increased risk of ovarian tumors in the provincial total, rising from 0.48 to 2.0 deaths per 10(5) women, while those located in the uterus show a virtually stable mortality over the 36 years under study (5.89/1950-59) (5.24/1980-85) x 10(5) women. In relation to other existing figures, our rates are, in the case of breast and ovarian tumors, similar to the global Spanish figures and lower than those for Cataluña and Navarra. In the case of tumors of the uterus, the adjusted mortality rates are lower than the national average and lower than any other Spanish figures available.

[Geographic study of cancer of the stomach in Spain in relation to agricultural activities]. / Estudio geográfico del cáncer gástrico en España en relación con actividades agrarias.

The Spanish provinces with the highest risk of gastric cancer (CG) are in the Castilian meseta, where grain raising predominates. In other countries, high risk areas also correspond to inland, high altitude regions, and in some cases, like Chile, abundant fertilizer consumption. The present study attempts to relate the risk of this tumor in Spain to different types of agricultural activity. Pearson's linear correlation coefficient was calculated between the mortality rate due to gastric cancer in each of the 50 Spanish provinces and the different types of farming and cattle raising activities. The correlation with grain raising on nonirrigated land was positive and significant for mortality in both men (p less than 0.001) and women (p less than 0.01). The correlation between mortality from gastric cancer and cattle raising, particularly sheep, was also positive and significant in both sexes (p less than 0.001). The proportion of the irrigated and nonirrigated fields dedicated to fruit trees correlated negatively with mortality in both sexes, also with a significant difference (p less than 0.01). The authors suggest the need for further epidemiological investigation in Spain, particularly in areas of high risk of gastric cancer, to identify precisely the risk factors that could be related to agricultural activities.

[Mortality trends caused by neoplasms of the digestive system. Soria, 1950-1985]. / Tendencias de mortalidad por neoplasias de aparato digestivo. Soria, 1950-1985.

The deaths caused by tumours of the digestive system (oesophagus, stomach, colon-rectum, gallbladder and pancreas) recorded in the province of Soria between 1950 and 1985 have been analyzed according to risk and mortality rates. Standardized (adjusted) rates in relation to sex and site of residence (urban-rural) of the deceased were calculated for the decades 1950-1959, 1960-1969, 1970-1979 and the period between 1980 and 1985. Standard errors were calculated to establish confidence limits according to Miettinen's method. The data were obtained from the death certificates of the various registries of the Soria province, including name and surnames, sex, age and site of the tumour according to the 9th revision of the International Classification of Diseases. There is a significant decrease in the mortality risk for tumours of the stomach in both sexes (p less than 0.01) and in liver tumours in females (p less than 0.01). On the other hand, there is an increased risk in both sexes for pancreatic cancer (p less than 0.05 M, p less than 0.01 F) and for oesophageal tumours in men (p less than 0.05). Similarly, during 1980-1985 men were at a significantly greater risk of dying from oesophageal, gastric and liver cancer (p less than 0.01) as well as rectum and colon (p less than 0.05). As far as stomach tumours are concerned there are significant differences between rural and urban areas both in males (p less than 0.01) and in females (p less than 0.05).

[Mortality trends in respiratory tract tumors. Soria, 1950-1985]. / Tendencias de mortalidad por tumores de aparato respiratorio. Soria, 1950-1985.

From 1950 to 1985, we have ascertained the causes of deaths caused by respiratory tract tumors of the: mouth, nose, pharynx, larynx, trachea, bronchi, lungs and pleura. They have been grouped by sexes and divided among three decades (1950-1979) and a six-year period (1980-1985), Gross Rates (G.R.) and Standard Rates (S.R.) with relation to said parameters to plot their Death Rate Tendencies. An increasing death rate is observed in men as related to tumors of the bronchi and lungs, with a higher risk statistics which are quite significant from 1950 to 1985. On the other hand, there is a decrease in the deaths of both sexes due to neoplasias of the larynx. With regard to the oral tumors, there has been a minimum increase in the men over the last few years, the female death rate being practically nil. There are differences between men and women which are quite significant statistically with regard to death rates related to tumors of the mouth, larynx, Bronchi and lungs. Nevertheless, given the method for collecting data, it can only be used as a guide, due to the turns affecting the sources of information.

[Histopathologic evaluation of death certificates in Soria in 1985]. / Valoración histopatológica de los boletines de defunción en Soria en 1985.

The aim of this paper is to evaluate the quality of the Death Certificates by means of the Death Statistics Bulletins, in their NEOPLASIC aspect in the year 1985 in the Province of Soria, determining the histopathologic confirmation of the deaths by means of the neoplasic patients' records in the two existing Pathology Services. An overall histologic verification of 80.76% is observed in the cases with an I.C. of +/- 4.79. In the case of BREAST, HEMATOLOGIC, OROPHARYNX, ENDOMETRIUM, ESOPHAGUS, OVARIAN, LARYNX and VULVA tumors, it is 100%. Whereas it is 14.3% in HEPATIC Tumors. Of the total of deaths registered in said year, the percentage of deaths caused by malignant neoplasias is over 26%, more than a fourth of which were Gastric. The preparation of the Death Certificates should be modified so that they can be objectively evaluated epidemiologically without bias or mistakes.