The impact of health insurance affiliation and socioeconomic status on cervical cancer survival in Bucaramanga,Colombia

Cervical cancer is still an important cause of death in countries like Colombia. We aimed to determine whether socioeconomic status of residential address (SES) and type of health insurance affiliation (HIA) might be associated with cervical cancer survival among women in Bucaramanga, Colombia. All patients residing in the Bucaramanga Metropolitan Area diagnosed with invasive cervical cancer (ICD-0–3 codes C53.X) between 2008 and 2016 (n = 725) were identified through the population-based cancer registry, with 700 women having follow-up data for >5 years (date of study closure: Dec 31, 2021), yielding an overall 5-year survival estimate (95 % CI) of 56.4 % (52.7 – 60.0 %). KM estimates of 5-year overall survival were obtained to assess differences in cervical cancer survival by SES and HIA. Multivariable Cox-proportional hazards modeling was also conducted, including interaction effects between SES and HIA. Five-year overall survival was lower when comparing low vs. high SES (41.9 % vs 57.9 %, p < 0.0001) and subsidized vs. contributive HIA (45.1 % vs 63.0 %, p < 0.0001). Multivariable Cox modeling showed increased hazard ratios (HR) of death for low vs. high SES (HR = 1.78; 95 % CI = 1.18–2.70) and subsidized vs. contributive HIA (HR = 1.44; 95 % CI = 1.13–1.83). The greatest disparity in HR was among women of low SES affiliated to subsidized HIA (vs. contributive HIA and high SES) (HR=2.53; 95 % CI = 1.62–3.97). Despite Colombia’s universal healthcare system, important disparities in cervical cancer survival by health insurance affiliation and socioeconomic status remain.     

The effect of the Flemish breast cancer screening program on breast cancer-specific mortality: A case-referent study

BackgroundBreast cancer screening programs were introduced in many countries worldwide following randomized controlled trials in the 1980s showing a reduction in breast cancer-specific mortality. However, their effectiveness remains debated and estimates vary. A breast cancer screening program was introduced in 2001 in Flanders, Belgium where high levels of opportunistic screening practices are observed. The effectiveness of this program was estimated by measuring its effect on breast cancer-specific mortality.MethodsWe performed a case-referent study to investigate the effect of participation in the Flemish population-based mammography screening program (PMSP) on breast cancer-specific mortality from 2005 to 2017. A multiple logistic regression model assessed the association between breast cancer-specific death and screening program participation status in the four years prior to (pseudo)diagnosis (yes/no), with adjustment for potential confounders (individual socio-economic position and calendar year of diagnosis) and stratified for age. In addition, we performed different sensitivity analyses.ResultsWe identified 1571 cases and randomly selected 6284 referents. After adjustment, women who participated in PMSP had a 51 % lower risk of breast cancer-specific mortality compared to those who did not (adjusted odds ratio [aOR] =0.49, 95 % CI: 0.44–0.55). Sensitivity analyses did not markedly change the estimated associations. Correction for self-selection bias reduced the effect size, but the estimate remained significant.ConclusionOur results indicate that in a context of high opportunistic screening rates, participation in breast cancer screening program substantially reduces breast cancer-specific mortality. For policy, these results should be balanced against the potential harms of screening, including overdiagnosis and overtreatment.     

Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation

Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to ‘austerity’, a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents. The ethanolic extract of Piper longum was found to have preferential cytotoxicity towards PANC-1 human pancreatic cancer cells in a nutrient-deprived medium (NDM). Further investigation led to the identification of pipernonaline ( 3 ) as the lead compound with the strongest anti-austerity activity, inducing cell death and inhibiting migration in a normal nutrient medium, as well as strongly inhibiting the Akt/mTOR/autophagy pathway. Therefore, pipernonaline ( 3 ) holds promise as a novel antiausterity agent for the treatment of pancreatic cancer.     

Radiation-induced changes in oral carcinoma cells – a multiparametric evaluation

The aim of this study was to see whether serial cytological evaluation of various cellular abnormalities in tumours from patients receiving fractionated radiotherapy can predict radio-response in oral carcinoma. Cytological assessment was carried out in scrape smears collected prior to and during the course of radiotherapy in 68 patients with squamous cell carcinoma of the oral cavity planned for radical radiotherapy with accelerated fraction schedule. Smears were evaluated for a set of 15 radiation-induced cellular abnormalities. The relationship between the cellular alterations and the cumulative radiation dose was analysed by Kruskal-Wallis one-way anova. The results showed that among the various quantifiable changes that occur in irradiated cancer cells, karyolysis, karyorrhexis, pyknosis, cytolysis, multinucleation, micronucleation and nuclear budding show significant increase depending on the dose of radiation. The radio-resistant group of patients exhibited a lesser degree of change compared with the radio-sensitive group. This suggests that radio-resistance may be due to the defective induction of cell damage and that these cytological features may have potential use as predictive markers of radio-sensitivity in oral carcinoma.     

Upregulation of Fas-induced apoptosis by interferon-γ accompanied by increased ICE expression in renal cell cancer cells

The integration of Fas/Apo-1 (CD95) by Fas ligand or anti-Fas antibody induces apoptosis, and this system plays a pivotal role for the lysis of target cells by cytotoxic T lymphocytes. Fas-mediated apoptosis is also increased by a prior incubation of Fas-bearing cells with interferon(IFN)-. Interleukin-1- converting enzyme (ICE) and/or CPP32, or other members of ICE family act as direct cell death executors downstream of this mechanism, and a tetrapeptide inhibitor of these cysteine proteases blocks Fas-mediated apoptosis. In this study, we examined the effect of IFN- on Fas-mediated apoptosis in ACHN cells. IFN- augmented apoptosis in a dose dependent manner and reached a plateau at 400 U/ml when exposed for 48 h before the end of culture. The kinetics revealed a significant increase in apoptosis after 24 h. Exposing ACHN cells to IFN- increased pro-ICE expression accompanied with a decrease of pro-CPP32. These results suggest that direct enhancement of ICE expression and/or upregulation of conversion of pro-CPP32 to active form increases Fas-mediated apoptosis by IFN- in ACHN cells.     

Interlaboratory Reproducibility In Reporting Inadequate Cervical Smears—A Multicentre Multinational Study

A set of 300 vaginal smears was interpreted by 13 cytologists from six European laboratories, who were requested to report inadequate and suboptimal smears. the set had been appropriately seeded to reach approximately 10% inadequate and 20% suboptimal smear frequency. According to the majority report, 230 smears were classified as adequate (76.7%), 43 as inadequate (14.3%), and 27 as suboptimal (9.0%). Agreement with the majority report ranged from 52% to 91% (average 78%). Kappa statistics for reporting inadequate smears showed a high level of agreement for five cytologists, and fair to good agreement for eight. In contrast, K statistics for reporting suboptimal smears showed fair to good agreement with the majority report only in five instances, whereas agreement was poor for eight cytologists. ‘Inadequate smear’rates may be used to compare the quality of smears received in different laboratories, as there is a high level of agreement among cytologists as to what constitutes an inadequate smear. However, this is not true for ‘suboptimal smear’ rates, and more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears: more precise reporting criteria must be defined and tested if an intermediate category is to be retained to report poor quality smears. Une série de 300 frottis cervico-vaginaux a été examinee par 13 cytologistes appartenant à 6 laboratoires européens auxquels il avait été demandé de signaler les frottis inadéquats et sub-optimaux. Cette série de frottis a été constituée de façon à atteindre approximativement une fréquence de 10% de frottis inadéquats et de 20% de frottis sub-optimaux. Si I'on considère les réponses faites par la majorité des cytologistes, 230 frottis ont été classés adéquats (76,7%), 43 classés inadéquats (14,3%), et 27 comme sub-optimaux (9,0%). La concordance avec les réponses de la majorité des cytologistes varie de 52%à 91% (moyenne 78%). Concernant le signalement des frottis inadéquats, le test Kappa est excellent pour 5 cytologistes et moyen à bon pour les 8 autres. Au contraire, pour le signalement des frottis sub-optimaux, le test Kappa montre un accord moyen à bon avec les réponses de la majorité seulement dans 5 cas alors que I'agrément est mauvais pour 8 cytologistes. La fréquence des frottis inadéquats peut être utilisée pour comparer la qualité de prélèvement du frottis dans différents laboratoires, alors que les comparaisons de la fréquence des frottis sub-optimaux sont discutables, du fait d'un biais de diagnostic évident. Des critéres plus précis pour le signalement des frottis sub-optimaux doivent étre définis et testés si cette catégorie doit être retenue pour rapporter les frottis de mauvaise qualité. 300 Abstriche wurden durch 13 Zytologen aus 6 europäischen Laboratorien hinsichtlich der Kriterien ‘unbrauchbar’und ‘suboptimal’beurteilt. Die Sammlung enthielt etwa 10% unbrauchbare und 20% suboptimale Präparate. Mehrheitlich wurden 230 Abstriche als auswertbar (76,7%), 43 als unbrauchbar (14,3%) und 27 als suboptimal (9,0%) bezeichnet. Die Statistik ergab hinsichtlich der unbrauchbaren Abstriche eine ausgezeichnete Ûbereinstimmung für 5 und eine gute Ûbereinstim-mung für 8 Zytologen. Demgegenüber zeigte sich hinsichtlich der Beurteilung suboptimal nur 5mal eine gute und 8mal eine schlechte Ûbereinstimmung. Damit ist die Kategorie suboptimal ungeeignet zum Vergleich und bedarf einer genaueren Definition wenn sie für die Qualitätskontrolle eingesetzt werden soll.     

Correlation of endoscopic cytology and histology in oesophageal cancer: results in Porto Alegre,RS—Brazil

A retrospective study of oesophageal cytopathology at the Hospital de Clínicas de Porto Alegre (HCPA), RS, Brazil, from 1989 to 1992 was made to assess the sensitivity, specificity, predictive values and accuracy of endoscopic cytology and biopsy; and study the correlation between cytopathological and histopathological diagnosis. Specimens from 94 patients were available for review. The final diagnosis was based on surgical pathology and follow up. The 81 patients with cancer of the oesophagus had the following sex distribution: 64 males and 17 females (a 3.7–1 ratio). No tumour was found in 13 patients. The following conclusions were made: (i) there is excellent correlation between cytology and histology in oesophageal lesions sampled by endoscopy; (ii) a correct positive cytologic report was obtained in 77 (95%) of the 81 proven oesophageal cancers; a false-negative or unsatisfactory result was given in four patients. A false-positive diagnosis of cancer was not made. There were 13 true-negative reports. These findings result in a sensitivity of 95% with 95% confidence intervals (CI) of 90.26–99.74%; a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.3–100%); a negative predictive value of 76% (CI of 55.7–96.3%); (iii) a correct positive histological report was obtained in 67 (83%) of the 81 proven oesophageal cancers; a false-negative or unsatisfactory result was given in 14 patients. A false-positive diagnosis of cancer was not made. There were 13 true-negative reports. These findings result in a sensitivity of 83% with 95% CI of 74.82–91.18%; a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.25–100%); a negative predictive value of 48% (CI of 29.16–64.84%); (iv) of 81 patients with proven cancer, in 79 (98%) at least one of the methods was positive. In only two patients with cancer were both methods negative. These findings result in a combined sensitivity of 98% (CI of 94.92–100%); a specificity of 100% (CI of 98.5–100%); a positive predictive value of 100% (CI of 99.31–100%); and a negative predictive value of 87% (CI of 70–100%). Our series confirms the value of the combined use of cytology and biopsy for the investigation of oesophageal lesions. However, it should be remembered that even with the combined use of cytology and biopsy there are some tumours that will be negative by both procedures: we had only two such cases, confirming the rarity of such an event.     

The Nucleotide Sequence of Human Acylamino Acid-Releasing Enzyme

The nucleotide sequence of a cDNA coding for the human acylaminoacid-releasing enzyme (AARE, also known as acylpeptide hydrolase)[EC 3.4.19.1] subunit has been determined. The amino acid sequenceof human AARE subunit deduced from its cDNA nucleotide sequenceshowed a high degree of identity (91.5%) with both the correspondingproteins from the pig and the rat. The AARE cDNA shows 99.2%identity with a 3.3 kb cDNA transcribed from a locus (DNF15S2)on the short arm of human chromosome 3, whose deletion is associatedwith small cell lung cancer, taking into consideration thatthe sequence of the 3.3-kb cDNA previously reported was causedby misreading.     

Mechanisms and pathogenesis of thyroid cancer in animals and man

The transformation of the normal fully differentiated thyroid follicular cell to the rapidly growing undifferentiated anaplastic thyroid carcinoma cell involves a number of stages which have been defined morphologically and are now being related to various growth pathways and to molecular biological defects. The two main factors involved in this transformation are growth stimulation and mutagenesis. Growth stimulation alone, through elevated TSH, can lead to the development of thyroid tumours, usually benign, and retaining TSH dependency in some cases. Mutagens alone, if growth is suppressed, do not produce tumours, the combination of mutagens and increased growth is a potent carcinogenic regime. Non-genotoxic carcinogenesis in the thyroid involves growth, without mutagenesis the agent often causes this through affecting one component of thyroid hormone synthesis or metabolism, leading to a fall in thyroid hormone levels and a rise in TSH. Growth stimulation increases the rate of cell division, and therefore increases the chance of a mutation. Continued growth increases the change of subsequent events, in particular loss of heterozygosity in a tumour suppressor gene. The main oncogenes involved in human thyroid carcinogens are ras in the follicular tumour pathway, and ret in the papillary carcinoma pathway. p53 is involved in the progression of either papillary or follicular adenoma to an undifferentiated carcinoma. In experimental thyroid carcinogenesis, ras is again involved, with a link between the mutagenic agent used and the type of ras gene showing mutation. Analysis of the involvement of different growth factors and oncogenes in thyroid carcinogenesis suggests that genes related to the two receptors concerned with normal TSH stimulated growth, TSH receptor and the IGF1 recpptor may be involved in the progression of thyroid tumours of follicular pathology. Several tyrosine kinase receptors with unknown ligands or of uncertain physiological function are linked to papillary carcinoma. The recent large increase in papillary carcinoma of the thyroid in children exposed to fallout from the Chernobyl nuclear accident underlines the importance of understanding the pathobiology of thyroid neoplasia.