Summary Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean ...countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population. This burgeoning cancer problem threatens to cause widespread suffering and economic peril to the countries of Latin America. Prompt and deliberate actions must be taken to avoid this scenario. Increasing efforts towards prevention of cancer and avoidance of advanced, stage IV disease will reduce suffering and mortality and will make overall cancer care more affordable. We hope the findings of our Commission and our recommendations will inspire Latin American stakeholders to redouble their efforts to address this increasing cancer burden and to prevent it from worsening and threatening their societies.
The purpose of this review was to describe cost-effectiveness and cost analysis studies across treatment modalities for squamous cell carcinoma of the head and neck (SCCHN), while placing their ...results in context of the current clinical practice. We performed a literature search in PubMed for English-language studies addressing economic analyses of treatment modalities for SCCHN published from January 2000 to March 2013. We also performed an additional search for related studies published by the National Institute for Health and Clinical Excellence in the United Kingdom. Identified articles were classified into 3 clinical approaches (organ preservation, radiation therapy modalities, and chemotherapy regimens) and into 2 types of economic studies (cost analysis and cost-effectiveness/cost-utility studies). All cost estimates were normalized to US dollars, year 2013 values. Our search yielded 23 articles: 13 related to organ preservation approaches, 5 to radiation therapy modalities, and 5 to chemotherapy regimens. In general, studies analyzed different questions and modalities, making it difficult to reach a conclusion. Even when restricted to comparisons of modalities within the same clinical approach, studies often yielded conflicting findings. The heterogeneity across economic studies of SCCHN should be carefully understood in light of the modeling assumptions and limitations of each study and placed in context with relevant settings of clinical practices and study perspectives. Furthermore, the scarcity of comparative effectiveness and quality-of-life data poses unique challenges for conducting economic analyses for a resource-intensive disease, such as SCCHN, that requires a multimodal care. Future research is needed to better understand how to compare the costs and cost-effectiveness of different modalities for SCCHN.
Summary Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology ...showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.
Summary Breast and cervical cancer are major threats to the health of women globally, particularly in low-income and middle-income countries. Radical progress to close the global cancer divide for ...women requires not only evidence-based policy making, but also broad multisectoral collaboration that capitalises on recent progress in the associated domains of women’s health and innovative public health approaches to cancer care and control. Such multisectoral collaboration can serve to build health systems for cancer, and more broadly for primary care, surgery, and pathology. This Series paper explores the global health and public policy landscapes that intersect with women’s health and global cancer control, with new approaches to bringing policy to action. Cancer is a major global social and political priority, and women’s cancers are not only a tractable socioeconomic policy target in themselves, but also an important Trojan horse to drive improved cancer control and care.
Abstract Introduction First-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment of advanced non–small-cell lung cancer (NSCLC) with EGFR -activating mutations ...improves outcomes compared with chemotherapy, but resistance develops in most patients. Compensatory signaling through type 1 insulin-like growth factor 1 receptor (IGF-1R) may contribute to resistance; dual blockade of IGF-1R and EGFR may improve outcomes. Patients and Methods We performed a randomized, double-blind, placebo-controlled phase 2 study of linsitinib, a dual IGF-1R and insulin receptor TKI, plus erlotinib versus placebo plus erlotinib in chemotherapy-naive patients with EGFR -mutation positive, advanced NSCLC. Patients received linsitinib 150 mg twice daily or placebo plus erlotinib 150 mg once daily on continuous 21-day cycles. The primary end point was progression-free survival (PFS). Results After randomization of 88 patients (44 each arm), the trial was unblinded early due to inferiority in the linsitinib arm. Median PFS for linsitinib versus placebo group was 8.4 versus 12.4 months (HR 1.37, P = .29). Overall response rate (47.7% vs. 75.0%, P = .02) and disease control rate (77.3% vs. 95.5%, P = .03) were also inferior. While most adverse events (AEs) were ≤ grade 2, linsitinib plus erlotinib was associated with increased AEs that led to decreased erlotinib exposure (median days, 228 vs. 305). No drug-drug interaction was suggested by pharmacokinetic and pharmacodynamic results. Conclusion Adding linsitinib to erlotinib resulted in inferior outcomes compared with erlotinib alone. Further understanding of the signaling pathways and a biomarker that can predict efficacy is needed prior to further clinical development of IGF-1R inhibitors in lung cancer.
Abstract Introduction Teeth are often included in the radiation field during head and neck radiotherapy, and recent clinical evidence suggests that dental pulp is negatively affected by the direct ...effects of radiation, leading to impaired sensitivity of the dental pulp. Therefore, this study aimed to investigate the direct effects of radiation on the microvasculature, innervation, and extracellular matrix of the dental pulp of patients who have undergone head and neck radiotherapy. Methods Twenty-three samples of dental pulp from patients who finished head and neck radiotherapy were analyzed. Samples were histologically processed and stained with hematoxylin-eosin for morphologic evaluation of the microvasculature, innervation, and extracellular matrix. Subsequently, immunohistochemical analysis of proteins related to vascularization (CD34 and smooth muscle actin), innervation (S-100, NCAM/CD56, and neurofilament), and extracellular matrix (vimentin) of the dental pulp was performed. Results The morphologic study identified preservation of the microvasculature, nerve bundles, and components of the extracellular matrix in all studied samples. The immunohistochemical analysis confirmed the morphologic findings and showed a normal pattern of expression for the studied proteins in all samples. Conclusions Direct effects of radiotherapy are not able to generate morphologic changes in the microvasculature, innervation, and extracellular matrix components of the dental pulp in head and neck cancer patients.
Abstract Objectives Recent studies suggested that head and neck radiotherapy increases active forms of matrix metalloproteinases (MMPs) in the dentin-enamel junction (DEJ) leading to enamel ...delamination and radiation-related caries (RRC). This study aimed to assess the expression and activity of the gelatinases MMP-2 and MMP-9 in the DEJ and dentin-pulp complex tissues of teeth irradiated in vivo. Study design Thirty-six teeth were studied including 19 irradiated and 17 non-irradiated controls. In situ zymography was used to investigate the gelatinolytic activity in the micromorphological components of enamel, DEJ, dentin-pulp complex, and caries. Immunohistochemical analysis was conducted on the demineralized samples to assess MMP-2 and MMP-9 expression levels in the DEJ, dentin-pulp complex components, and caries. Results No statistically significant differences were detected in MMP-2 expression levels or in gelatinolytic activity ( p > 0.05) between groups. Odontoblast MMP-9 expression was reduced in the irradiated group ( p = 0.02). Conclusions The study rejected the hypothesis that MMP-2 and MMP-9 would be overexpressed or more activated in the DEJ and dentin-pulp complex of irradiated teeth. Direct effects of radiation shouldn’t be regarded as an independent factor for explaining RRC onset and progression.
We sought to determine the value of dobutamine versus adenosine real-time myocardial perfusion (MP) echocardiography for detecting coronary artery disease and the value of quantitative analysis of MP ...over electrocardiography, wall motion, and qualitative MP. We studied 54 patients by real-time MP echocardiography and coronary angiography. Replenishment velocity (beta) and an index of myocardial blood flow (A(n)xbeta) were derived from quantitative MP. During dobutamine stress, beta (1.7 +/- 0.7 vs 2.7 +/- 1.2; P < .001) and A(n)xbeta (2.2 +/- 1.0 vs 3.5 +/- 1.6; P < .001) reserves were lower in patients with coronary artery disease. The same was observed with adenosine for beta (1.7 +/- 0.8 vs 2.5 +/- 1.1; P < .001) and A(n)xbeta (1.9 +/- 0.7 vs 3.2 +/- 1.4; P < .001) reserves. Accuracy of electrocardiography, wall motion, qualitative MP, and quantitative MP were 61%, 76%, 76%, and 80% for dobutamine and 70%, 70%, 76%, and 80% for adenosine, respectively. Quantitative MP had incremental diagnostic value over other variables during dobutamine (chi(2) 23.7-38.4; P < .001) and adenosine (chi(2) 26.7-59.4; P < .001). In conclusion, dobutamine and adenosine real-time MP echocardiography hold similar accuracy for detecting coronary artery disease. Quantitative MP provides incremental diagnostic information over other variables.
Hydrochlorothiazide has a negative influence on penile erection but little is known about the mechanism(s) involved.
To characterize the effects of this diuretic on mouse corpus cavernosum (CC) ...smooth muscle in vitro and ex vivo.
CC strips of C57BL/6 mice (12–16 weeks old) were mounted in organ baths containing Krebs-Henseleit solution and tissue reactivity was evaluated. Expression of genes encoding diuretic targets and enzymes involved in penile erection were evaluated by polymerase chain reaction.
Stimulation-response curves to phenylephrine (10 nmol/L–100 μmol/L) or to electrical field stimulation (1–32 Hz) were constructed, with or without hydrochlorothiazide. Strips of CC from mice after long-term hydrochlorothiazide treatment (6 mg/kg/day for 4 weeks) with or without amiloride (0.6 mg/kg/day for 4 weeks) in vivo also were studied. Nitric oxide and Rho-kinase pathways were evaluated.
Hydrochlorothiazide (100 μmol/L) increased the maximum response to phenylephrine by 64% in vitro. This effect was unaffected by the addition of indomethacin (5 μmol/L) but was abolished by N(ω)-nitro-L-arginine methyl ester (100 μmol/L). Hydrochlorothiazide (100 μmol/L) potentiated electrical field stimulation-induced contraction in vitro, but not ex vivo. Long-term treatment with hydrochlorothiazide increased the maximum response to phenylephrine by 60% and resulted in a plasma concentration of 500 ± 180 nmol/L. Amiloride (100μmol/L) caused rightward shifts in concentration-response curves to phenylephrine in vitro. Long-term treatment with hydrochlorothiazide plus amiloride did not significantly increase the maximum response to phenylephrine (+13%). Reverse transcriptase polymerase chain reaction did not detect the NaCl cotransporter in mouse CC. Hydrochlorothiazide did not change Rho-kinase activity, whereas amiloride decreased it in vitro and ex vivo (approximately 18% and 24% respectively). A 40% decrease in Rock1 expression also was observed after long-term treatment with hydrochlorothiazide plus amiloride.
Hydrochlorothiazide potentiates contraction of smooth muscle from mouse CC. These findings could explain why diuretics such as hydrochlorothiazide are associated with erectile dysfunction.
Summary Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available ...evidence for optimum management of colon cancer—in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases—and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.
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