Cancer in Costa Rica

Artículo científico -- Universidad de Costa Rica. Isntituto de Investigaciones en Salud, 1989Data from the national tumor registry of Costa Rica for the yeas 1979-1983 have been used to calculate incidence rates for the major cancer sites by age, sex, urban-rural residence, and geographic region. Recent trends in mortality rates are also presented. Results are compared Mutilate from elsewhere in Latin America, U. S. A., Europe, and Japan. Stomach cancer is the most frequent neoplasm in Costa Rift; although rates are declining, they are second only to those observed in Japan. There are marked variations in risk by region, suggesting important enviromental influences in etiology. The cervix is the major female site; rates are declining in young women, probably doe to the introduction of saweniog programs, although these do not seem to account for the geogeaphic variations in invasive cancer incidence. Breast and prostate cancer show moderate rates, while those for colon and rectum cancer are low; increases in mortality rates for these sites are small, and involve mainly the older age groups. In contrast, rates of lung cancer are inaeasin ' g dramatically in both sexes. In the childhood age group, very high incidence rates are observed for two neoplasms: Hodgkin's disease and acute lymphocytic leukemia.Universidad de Costa Rica. Instituto de Investigaciones en Salud.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto de Investigaciones en Salud (INISA

Cancer survival: left truncation and comparison of results from hospital-based cancer registry and population-based cancer registry

BackgroundCancer survival is an important indicator for evaluating cancer prognosis and cancer care outcomes. The incidence dates used in calculating survival differ between population-based registries and hospital-based registries. Studies examining the effects of the left truncation of incidence dates and delayed reporting on survival estimates are scarce in real-world applications.MethodsCancer cases hospitalized at Nantong Tumor Hospital during the years 2002–2017 were traced with their records registered in the Qidong Cancer Registry. Survival was calculated using the life table method for cancer patients with the first visit dates recorded in the hospital-based cancer registry (HBR) as the diagnosis date (OSH), those with the registered dates of population-based cancer (PBR) registered as the incidence date (OSP), and those with corrected dates when the delayed report dates were calibrated (OSC).ResultsAmong 2,636 cases, 1,307 had incidence dates registered in PBR prior to the diagnosis dates of the first hospitalization registered in HBR, while 667 cases with incidence dates registered in PBR were later than the diagnosis dates registered in HBR. The 5-year OSH, OSP, and OSC were 36.1%, 37.4%, and 39.0%, respectively. The “lost” proportion of 5-year survival due to the left truncation for HBR data was estimated to be between 3.5% and 7.4%, and the “delayed-report” proportion of 5-year survival for PBR data was found to be 4.1%.ConclusionLeft truncation of survival in HBR cases was demonstrated. The pseudo-left truncation in PBR should be reduced by controlling delayed reporting and maximizing completeness. Our study provides practical references and suggestions for evaluating the survival of cancer patients with HBR and PBR

Adjuvant radiotherapy and chemotherapy in breast cancer: 30 year follow-up of survival

BACKGROUND:The long term outcome (more than 15 years) of adjuvant treatment in patients with primary operable breast cancer has rarely been examined.METHODS:A randomised clinical trial of radiotherapy, chemotherapy (28 day cycles of cyclophosphamide, methotrexate and 5-fluorouracil) or both on women with primary operable breast cancer (n = 322) was followed-up for a median of 27 years.RESULTS:260 (81%) patients died, 204 (78%) from breast cancer. Cancer specific survival (SE) at 10 years, 20 years and 30 years was 41 (3)%, 34 (3)% and 33 (3)% respectively. Presence of more than 3 involved lymph nodes increased cancer-specific mortality (HR 1.88, 95% CI 1.34-2.63) after adjustment for age, socio-economic deprivation and adjuvant treatment. Both age (HR 1.63, 95% CI 1.19-2.22) and involved lymph nodes (HR 1.59, 95% CI 1.17-2.14) were significant predictors of all-cause mortality after adjustment for other factors. There was no significant difference in all-cause or cancer-specific survival between patients in each of the 3 treatment arms.CONCLUSIONS:The present study highlights the long term impact of node positive disease but does not indicate that any regimen was associated with significantly better long-term surviva

Understanding pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug distribution within the CSF space for intrathecal drugs

We introduce how biophysical modeling in pharmaceutical research and development, combining physiological observations at the tissue, organ and system level with selected drug physiochemical properties, may contribute to a greater and non-intuitive understanding of drug pharmacokinetics and therapeutic design. Based on rich first-principle knowledge combined with experimental data at both conception and calibration stages, and leveraging our insights on disease processes and drug pharmacology, biophysical modeling may provide a novel and unique opportunity to interactively characterize detailed drug transport, distribution, and subsequent therapeutic effects. This innovative approach is exemplified through a three-dimensional (3D) computational fluid dynamics model of the spinal canal motivated by questions arising during pharmaceutical development of one molecular therapy for spinal cord injury. The model was based on actual geometry reconstructed from magnetic resonance imaging data subsequently transformed in a parametric 3D geometry and a corresponding finite-volume representation. With dynamics controlled by transient Navier–Stokes equations, the model was implemented in a commercial multi-physics software environment established in the automotive and aerospace industries. While predictions were performed in silico, the underlying biophysical models relied on multiple sources of experimental data and knowledge from scientific literature. The results have provided insights into the primary factors that can influence the intrathecal distribution of drug after lumbar administration. This example illustrates how the approach connects the causal chain underlying drug distribution, starting with the technical aspect of drug delivery systems, through physiology-driven drug transport, then eventually linking to tissue penetration, binding, residence, and ultimately clearance. Currently supporting our drug development projects with an improved understanding of systems physiology, biophysical models are being increasingly used to characterize drug transport and distribution in human tissues where pharmacokinetic measurements are difficult or impossible to perform. Importantly, biophysical models can describe emergent properties of a system, i.e. properties not identifiable through the study of the system’s components taken in isolation

The Odyssey of Dental Anxiety: From Prehistory to the Present. A Narrative Review

Dental anxiety (DA) can be considered as a universal phenomenon with a high prevalence worldwide; DA and pain are also the main causes for medical emergencies in the dental office, so their prevention is an essential part of patient safety and overall quality of care. Being DA and its consequences closely related to the fight-or-flight reaction, it seems reasonable to argue that the odyssey of DA began way back in the distant past, and has since probably evolved in parallel with the development of fight-or-flight reactions, implicit memory and knowledge, and ultimately consciousness. Basic emotions are related to survival functions in an inseparable psychosomatic unity that enable an immediate response to critical situations rather than generating knowledge, which is why many anxious patients are unaware of the cause of their anxiety. Archeological findings suggest that humans have been surprisingly skillful and knowledgeable since prehistory. Neanderthals used medicinal plants; and relics of dental tools bear witness to a kind of Neolithic proto-dentistry. In the two millennia BC, Egyptian and Greek physicians used both plants (such as papaver somniferum) and incubation (a forerunner of modern hypnosis, e.g., in the sleep temples dedicated to Asclepius) in the attempt to provide some form of therapy and painless surgery, whereas modern scientific medicine strongly understated the role of subjectivity and mind-body approaches until recently. DA has a wide range of causes and its management is far from being a matter of identifying the ideal sedative drug. A patient's proper management must include assessing his/her dental anxiety, ensuring good communications, and providing information (iatrosedation), effective local anesthesia, hypnosis, and/or a wise use of sedative drugs where necessary. Any weak link in this chain can cause avoidable suffering, mistrust, and emergencies, as well as having lifelong psychological consequences. Iatrosedation and hypnosis are no less relevant than drugs and should be considered as primary tools for the management of DA. Unlike pharmacological sedation, they allow to help patients cope with the dental procedure and also overcome their anxiety: achieving the latter may enable them to face future dental care autonomously, whereas pharmacological sedation can only afford a transient respite

Effect of educational intervention on medication timing in Parkinson's disease: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Medicine usage in Parkinson's disease patients is often imperfect, in particular irregular timing of medication. The effect of informing Parkinson's disease patients about the continuous dopaminergic hypothesis (to encourage regular medicine intake) on medication adherence and motor control was tested.</p> <p>Methods</p> <p>Patients were randomised either to the active group (receiving the intervention) or control group (no extra information). Antiparkinson medicine usage was monitored for 3 months before and after the intervention using electronic pill bottles which record the date and time of opening (MEMS^®, Aardex, Switzerland) and data used to calculate the percentage of doses taken at correct time intervals.</p> <p>Results</p> <p>43 patients (52%) were randomised to active counselling, and 40 (48%) were controls (standard management). The intervention effect (difference in timing adherence pre- to post-intervention between the 2 groups) was 13.4% (CI 5.1 to 21.7), p = 0.002. Parkinson motor scores did not change significantly (active group 0.1, CI -3.4 to 3.7) versus controls (4.5, CI 1.6 to 7.1), p = 0.06.</p> <p>Conclusion</p> <p>Timing adherence, but not motor scores, improves by providing patients with extra information. Therapy timing is of potential importance in Parkinson's disease management.</p> <p>Trial registration number</p> <p>NCT00361205</p

A Granulin-Like Growth Factor Secreted by the Carcinogenic Liver Fluke, Opisthorchis viverrini, Promotes Proliferation of Host Cells

The human liver fluke, Opisthorchis viverrini, infects millions of people throughout south-east Asia and is a major cause of cholangiocarcinoma, or cancer of the bile ducts. The mechanisms by which chronic infection with O. viverrini results in cholangiocarcinogenesis are multi-factorial, but one such mechanism is the secretion of parasite proteins with mitogenic properties into the bile ducts, driving cell proliferation and creating a tumorigenic environment. Using a proteomic approach, we identified a homologue of human granulin, a potent growth factor involved in cell proliferation and wound healing, in the excretory/secretory (ES) products of the parasite. O. viverrini granulin, termed Ov-GRN-1, was expressed in most parasite tissues, particularly the gut and tegument. Furthermore, Ov-GRN-1 was detected in situ on the surface of biliary epithelial cells of hamsters experimentally infected with O. viverrini. Recombinant Ov-GRN-1 was expressed in E. coli and refolded from inclusion bodies. Refolded protein stimulated proliferation of murine fibroblasts at nanomolar concentrations, and proliferation was inhibited by the MAPK kinase inhibitor, U0126. Antibodies raised to recombinant Ov-GRN-1 inhibited the ability of O. viverrini ES products to induce proliferation of murine fibroblasts and a human cholangiocarcinoma cell line in vitro, indicating that Ov-GRN-1 is the major growth factor present in O. viverrini ES products. This is the first report of a secreted growth factor from a parasitic worm that induces proliferation of host cells, and supports a role for this fluke protein in establishment of a tumorigenic environment that may ultimately manifest as cholangiocarcinoma

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

<p>Abstract</p> <p>Background</p> <p>A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC.</p> <p>Methods</p> <p>PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome.</p> <p>Results</p> <p>When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk.</p> <p>Conclusion</p> <p>ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.</p