Effect of consumption of blue maize tortilla on anxiety-like behaviour, learning, memory and hippocampal BDNF expression in a chronic stress model in rats.

BACKGROUND: Pigmented maize consumption is of much interest because of its high anthocyanin content and multiple health benefits. OBJETIVES: This study was aimed to assess the effect of consuming blue maize tortillas on the anxiolytic capacity, preserve emotional memory, and the expression of brain-derived neurotrophic factor (BDNF) in rats subjected to chronic stress. METHODS: Sixty-four 3-month-old male Wistar rats were used, divided into eight groups (n = 8). Four groups were subjected to chronic stress by movement restriction (7 h/daily/7 consecutive days) and the remaining four groups were subjected to standard management. The treatments were commercial food, blue tortilla, anthocyanin extract, or white tortilla, administered for nine weeks to stressed or unstressed animals. In the eighth week, the animals were subjected to the restraint stress model. Subsequently, anxiety-like behaviour was assessed using the elevated plus-maze, and memory and emotional learning were evaluated by the step-down passive avoidance test. The animals were then sacrificed to quantify the relative expression of hippocampal BDNF by RT-qPCR. RESULTS: The consumption of anthocyanin extract or tortilla made with blue corn decreased anxiety-like behaviours, additionally, it improved the ability to retain emotionally relevant information, and it upregulated BDNF mRNA expression. PERSPECTIVE: Thus, the analyse of the impact of blue tortilla consumption on the nervous system is now necessary to guarantee the nutraceutical value of this food.

Patterns of care among patients receiving sequential targeted therapies for advanced renal cell carcinoma: A retrospective chart review in the USA.

OBJECTIVES: To assess real-world treatment patterns of targeted therapies after failure of first-line tyrosine kinase inhibitors in patients with advanced renal cell carcinoma. METHODS: A large, retrospective review of medical charts of patients with advanced renal cell carcinoma in the USA was carried out. Descriptive statistics were used to summarize physicians' and patients' characteristics, treatment sequences, and reasons for treatment choices. P-values were calculated using χ2 -tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. A descriptive comparison was carried out between current results and those of a previous treatment pattern study conducted in 2012 to identify changes in treatment patterns over time. RESULTS: Sunitinib and everolimus remained the most commonly-used first and second targeted therapies, respectively. Among patients who continued to a third targeted therapy, everolimus and axitinib were the most commonly-used treatments after second targeted therapy with a tyrosine kinase inhibitor and a mammalian target of rapamycin inhibitor, respectively. The use of pazopanib as first targeted therapy, and of axitinib and sorafenib as second targeted therapies, increased over time. Efficacy, treatment guidelines and a different mechanism of action were the main reasons given by physicians for choosing among second targeted therapies after failure of a first tyrosine kinase inhibitor. CONCLUSIONS: The results of the present study document patterns of care during a period of rapid and ongoing therapeutic advancement in advanced renal cell carcinoma. Sequencing of therapies warrants ongoing analysis in light of new agents entering the advanced renal cell carcinoma treatment landscape.

Persistency with zoledronic acid is associated with clinical benefit in patients with multiple myeloma.

Zoledronic acid (ZOL), an intravenous bisphosphonate, has been shown to reduce and delay the incidence of skeletal-related events (SREs) in multiple myeloma (MM) patients with bone disease. A retrospective claims-based analysis was conducted that used two distinct US managed care databases to examine the relationship between persistency with ZOL and clinical benefit. Patients >18 years, diagnosed with MM, and with at least one claim for ZOL (or a claim for malignant bone disease and ZOL initiation within 30 days) between 1/1/2001 and 12/31/2006 were included. Patients were evaluated for incidence of SREs and for mortality. Treatment persistency was defined as the absence of a >45 day gap between ZOL administrations. Of 1,655 patients in this analysis, 1,060 received ZOL and 595 received no intravenous bisphosphonate therapy. Compared with patients not receiving bisphosphonate therapy, ZOL-treated patients had lower incidences of SREs (P < 0.0001) and death (P = 0.0001). Longer persistency with ZOL was associated with lower risks of SREs (P = 0.001), fracture (P = 0.003), and death (P = 0.002) versus shorter persistency. Patients who were persistent with ZOL for ≥1.5 years had an incidence of 15.0 SREs and 6.2 fractures per 100 person-years. Patients who were persistent for 31-90 days had an incidence of 24.6 SREs and 14.0 fractures per 100 person-years, and patients not receiving intravenous bisphosphonates had an incidence of 32.2 SREs and 16.9 fractures per 100 person-years. These data from a real-world setting indicate that among MM patients, longer persistency with ZOL was associated with a lower risk of SREs and fracture.

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

BACKGROUND: When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. OBJECTIVE: To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. METHODS: The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. RESULTS: Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1 year were $34,141, $19,371, and $17,506 higher, respectively. Everolimus had similar OS and lower costs compared with axitinib. The additional cost per month of OS was $48,773 for cabozantinib and $24,214 for nivolumab versus everolimus. The additional treatment cost with cabozantinib, nivolumab, or axitinib versus everolimus for each additional month of PFS was estimated at $21,338, $64,570, and $35,012, respectively. Over 2 years, the additional costs per additional month of OS for nivolumab and axitinib versus everolimus were similar to the 1-year analysis; for cabozantinib, the cost was lower. Results were sensitive to changes in mean OS, mean PFS, therapy duration, and drug costs estimates. CONCLUSIONS: Everolimus for second-line mRCC was associated with similar OS and lower costs compared with axitinib over 1- and 2-year horizons. The additional cost per additional month of OS and PFS associated with cabozantinib or nivolumab versus everolimus creates a metric for evaluating the cost of second-line therapies in relation to their respective treatment effects. DISCLOSURES: Funding for this research was provided by Novartis, which was involved in all stages of study research and manuscript preparation. Ghate and Perez are employees of Novartis and own stock/stock options. Swallow, Messali, McDonald, and Duchesneau are employees of Analysis Group, which has received consultancy fees from Novartis. Study concept and design were contributed by Swallow, Messali, Ghate, and Perez, along with McDonald and Duchesneau. Swallow, Messali, McDonald, and Duchesneau collected the data, and all authors participated in data interpretation. The manuscript was written by Swallow, Messali, and Ghate, along with the other authors, and revised by Swallow, Messali, Ghate, and Perez. A synopsis of the current research was presented in poster format at the 15th International Kidney Cancer Symposium on November 4-5, 2016, in Miami, Florida.

Real-World Economic Outcomes During Time on Treatment Among Patients Who Initiated Sunitinib or Pazopanib as First Targeted Therapy for Advanced Renal Cell Carcinoma: A Retrospective Analysis of Medicare Claims Data.

BACKGROUND: The median age at renal cell carcinoma (RCC) diagnosis is 64 years. However, few studies have assessed the real-world time on treatment (TOT), health resource utilization (HRU), costs, or treatment compliance associated with targeted therapy use among patients in this age group with RCC. OBJECTIVE: To assess the HRU, costs, and compliance during TOT among Medicare patients aged ≥ 65 years with advanced RCC (aRCC) who initiated first targeted therapy with pazopanib or sunitinib. METHODS: Patients with aRCC were identified in the 100% Medicare + Part D databases administered by the Centers for Medicare & Medicaid Services. Eligible patients initiated first targeted therapy with sunitinib or pazopanib (index drug) on or after their first diagnosis of secondary neoplasm between October 19, 2009, and January 1, 2014, and were aged ≥ 65 years as of 1 year before first targeted therapy initiation (index date). Included patients were stratified into pazopanib and sunitinib cohorts based on first targeted therapy and matched 1:1 on baseline characteristics using propensity scores. TOT was defined as the time from the index date to treatment discontinuation (prescription gap > 90 days) or death. Compliance was defined as the ratio of drug supply days to TOT. Monthly all-cause costs and costs associated with RCC diagnosis (medical and pharmacy in 2015 U.S. dollars) and HRU (inpatient [admissions, readmissions, and days], outpatient, and emergency room visits) were assessed in the 1-year post-index period during TOT. Matched cohorts' TOT was compared using Kaplan-Meier analyses and univariable Cox models, and compliance, HRU, and costs were compared using Wilcoxon signed-rank tests. RESULTS: Of 1,711 included patients, 526 initiated pazopanib and 1,185 initiated sunitinib. Before matching, more patients in the pazopanib cohort were white, diagnosed in 2010-2014 versus 2006-2009, and had lung metastases compared with the sunitinib cohort (all P < 0.05). The pazopanib cohort also had higher mean outpatient visits and costs but lower mean total all-cause pharmacy costs, than the sunitinib cohort (all P < 0.05). After matching, the pazopanib and sunitinib cohorts had similar characteristics (mean age 75 years, 58% male, and Charlson Comorbidity Index score of 9.2 in both cohorts) and median TOT (4.8 and 4.1 months, respectively). Among the 522 matched pairs, pazopanib was associated with significantly lower total all-cause health care costs ($8,527 vs. $10,924, respectively [mean difference = $2,397]); total medical costs ($3,991 vs. $5,881, respectively, [$1,890]); and inpatient costs ($2,040 vs. $3,731, respectively, [$1,692]; all P < 0.01) compared with sunitinib. Patients receiving pazopanib had significantly fewer inpatient admissions (0.179 vs. 0.289, respectively) and days (1.063 vs. 1.904, respectively; both P < 0.01) than patients receiving sunitinib. Mean treatment compliance was lower for the pazopanib versus sunitinib cohort (0.91 vs. 0.94, respectively; P < 0.01). CONCLUSIONS: In this retrospective analysis of Medicare patients with aRCC from a TOT perspective, first targeted therapy with pazopanib was associated with significantly lower all-cause health care costs and HRU, but lower compliance, compared with sunitinib. DISCLOSURES: Funding for this research was provided by Novartis Pharmaceuticals. The sponsor was involved in all stages of the study's conduct and reporting. Vogelzang has been a consultant for Novartis, Amgen, Celgene, Medivation, Eisai, Exelixis, and Roche; has spoken at Novartis, Astellas, Johnson and Johnson, Pfizer, Dendreon, Bayer/Algeta, GSK, and Veridex/Janssen; and has received research support from Novartis, Bayer, Exelixis, Progenics, Bavarian Nordic, and Viamet. Pal has been a consultant for Novartis, Pfizer, Aveo, Dendreon, and Myriad and has spoken at Novartis, Pfizer and Medivation. Agarwal has been a consultant or advisor for Novartis, Pfizer, Exelixis, Cerulean Pharma, Medivation, Eisai, and Argos Therapeutics. Swallow, Peeples, Zichlin, and Meiselbach are employees of Analysis Group, which received consultancy fees from Novartis for this project. Li was an employee of Analysis Group during the conduct of this study. Ghate is an employee of Novartis and owns stock/stock options. Perez was an employee of Novartis during the conduct of this study. A synopsis of the economic outcomes was presented at the Academy of Managed Care Pharmacy Nexus 2017 in Denver, Colorado, during March 27-30, 2017. A synopsis of the clinical outcomes was presented at the 22nd ISPOR Annual International Meeting in Boston, Massachusetts, during May 20-24, 2017.

Results of a Qualitative Study to Develop a Patient Reported Outcome Measure for Patients with 4 Subtypes of Soft Tissue Sarcoma.

OBJECTIVE: The objective of this research was to develop a disease-specific symptom inventory for soft tissue sarcoma. METHODS: Literature review and clinical expert and patient interviews were conducted to determine disease-specific symptoms important to patients with one of the four STS subtypes. Clinical experts identified the most relevant STS symptom items from the item pool developed from literature review. Concept elicitation interviews were conducted with patients to elicit their STS symptom experiences followed by a completion of the draft symptom list via web survey. A cognitive interview was conducted on the comprehension and importance of the symptom items. RESULTS: Eighty-three symptom items were compiled and discussed with three clinical experts who identified 26 symptoms specific to the four STS subtypes. A total sample of 27 STS participants with self-reported leiomyosarcoma (74%), undifferentiated sarcoma (15%), synovial sarcoma (7%), or liposarcoma (4%) diagnosis completed the web survey and 10 were interviewed. The draft 12-item STS-specific symptom inventory includes abdominal pain, pressure in abdomen, early satiety, bloating, gastrointestinal pain, muscle pain, bone pain, heavy menstrual flow, shortness of breath, chest pain, cough, and painful menstruation. CONCLUSION: A number of symptoms are common across STS subtypes and may form a single STS symptom inventory.

Clinical and Economic Outcomes in Elderly Advanced Renal Cell Carcinoma Patients Starting Pazopanib or Sunitinib Treatment: A Retrospective Medicare Claims Analysis.

INTRODUCTION: Studies indicate similar survival and toxicity between pazopanib and sunitinib, but few have examined real-world outcomes among elderly patients with advanced renal cell carcinoma (RCC). The purpose of this retrospective claims analysis was to assess real-world overall survival (OS), healthcare resource utilization (HRU), and healthcare costs (both all-cause and associated with RCC diagnosis) among elderly advanced RCC patients starting pazopanib or sunitinib treatment. METHODS: Advanced RCC patients aged 65 years or older who started first-line treatment with pazopanib or sunitinib (index drug; the initiation date was the index date) were identified from the 100% Medicare database plus Part D linkage (January 1, 2006 to December 31, 2014). Patients were stratified by index drug and matched 1:1 with use of propensity scores based on baseline characteristics. OS was assessed from the index date to death and compared by Kaplan-Meier analyses and univariable Cox models; patients were censored at the end of eligibility/data. Monthly HRU and costs from an intent-to-treat perspective were compared by Wilcoxon signed-rank tests. RESULTS: Baseline characteristics were balanced after matching (both N = 522). Treatment with pazopanib was associated with significantly longer median OS compared with treatment with sunitinib (18.2 months vs 14.6 months, respectively; log-rank p = 0.015). Pazopanib was associated with significantly lower monthly all-cause costs compared with sunitinib ($8845 vs $10,416, respectively), as well as lower inpatient costs associated with RCC diagnosis ($1542 vs $2522), fewer monthly inpatient admissions (0.179 vs 0.262), and shorter length of inpatient stay (1.375 days vs 1.883 days; all p ≤ 0.004). CONCLUSIONS: Among elderly Medicare patients with advanced RCC, first-line pazopanib tretament was associated with significantly longer OS, as well as lower healthcare costs and HRU, compared with first-line sunitinib treatment.

Real-World Survival Outcomes and Prognostic Factors Among Patients Receiving First Targeted Therapy for Advanced Renal Cell Carcinoma: A SEER-Medicare Database Analysis.

BACKGROUND: The real-world survival outcomes and prognostic factors among patients receiving first-line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. PATIENTS AND METHODS: Adult patients diagnosed with RCC and treated with first-line targeted therapy were identified from the Surveillance, Epidemiology, and End Results-Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006-2009) or late (2010-2012) targeted therapy era cohorts by the year of the first-line targeted therapy initiation. Overall survival (OS) was measured from first-line targeted therapy initiation and compared between the 2 cohorts using Kaplan-Meier analyses. The prognostic factors for OS were assessed using a multivariable-adjusted Cox model. RESULTS: A total of 604 and 641 aRCC patients (mean age, 68 years; ∼60% male in both cohorts) initiated first-line targeted therapy during the early and late targeted therapy eras, respectively. OS was significantly longer in the late than in the early targeted therapy era. Higher tumor grades (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.31-2.00) and lung (HR, 1.27; 95% CI, 1.06-1.53), bone (HR, 1.37; 95% CI, 1.13-1.66), and liver (HR, 1.42; 95% CI, 1.10-1.84) metastases were associated with significantly shorter OS. Previous nephrectomy (HR, 0.55; 95% CI, 0.42-0.72) and pazopanib as first-line targeted therapy relative to sorafenib (HR, 0.56; 95% CI, 0.37-0.85) or sunitinib (HR, 0.65; 95% CI, 0.44-0.95) were associated with significantly longer OS. CONCLUSION: The results of these real-world analyses suggest progress in aRCC management and identified positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bone, or liver metastasis) prognostic factors among patients receiving first-line targeted therapy.

Comparative effectiveness of everolimus and axitinib as second targeted therapies for metastatic renal cell carcinoma in the US: a retrospective chart review.

Background Second targeted therapies for metastatic renal cell carcinoma (mRCC) include mammalian target of rapamycin inhibitors (mTORis) and tyrosine kinase inhibitors (TKIs). This observational study compares overall survival (OS) and progression-free survival (PFS) of patients treated with everolimus (an mTORi) and axitinib (a TKI) following first TKI, and assesses the impact of type and duration of first TKI on the relative effectiveness of these second targeted therapies. Methods Retrospective reviews of medical records were conducted by medical oncologists or hematologists/oncologists recruited from a nationwide panel. Included patients with mRCC were required to have discontinued a first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons, and to have initiated everolimus or axitinib as second targeted therapy between February 2012 and January 2013. OS and PFS were compared between patients treated with everolimus vs. axitinib using multivariable Cox proportional hazards regression models. Comparative results were also stratified by type and duration of first TKI. Results Included patients (n = 325 for everolimus and n = 127 for axitinib) had a mean age of 61 years and 31% were female. Sunitinib was the most commonly used first TKI (73%). After adjusting for patient characteristics, no statistically significant differences were observed in OS or PFS between everolimus and axitinib. When stratifying by type and duration of first TKI, there was no statistically significant difference in OS between everolimus and axitinib in all subgroups except for patients with <6 months on sunitinib or sorafenib as first TKI. No significant difference in PFS was observed in any subgroup. Limitations Important limitations include potential missing or inaccurate data in medical charts, and confounding due to unobserved factors. Conclusions In this retrospective chart review, no significant differences were detected in OS or PFS between axitinib and everolimus as second targeted therapy. Longer duration of first TKI was not associated with increased effectiveness of subsequent axitinib compared to everolimus.

Real-World Effectiveness of Everolimus Subsequent to Different First Targeted Therapies for the Treatment of Metastatic Renal Cell Carcinoma: Synthesis of Retrospective Chart Reviews.

BACKGROUND: The effect of first targeted therapy on outcomes with second targeted therapy for metastatic renal cell carcinoma is not well known. The purpose of this study was to compare outcomes for patients receiving a second targeted therapy with everolimus by type of first targeted therapy. PATIENTS AND METHODS: Data were drawn from 3 separate retrospective chart reviews conducted in 2011, 2012, and 2014. Inclusion criteria and study design were similar across the 3 studies. To be included in this analysis, patients had to meet the following criteria: aged ≥ 18 years; received first targeted therapy with pazopanib, sunitinib, or sorafenib; and received second targeted therapy with everolimus. Overall survival, time to treatment failure, and time to treatment discontinuation outcomes were measured from second targeted therapy initiation. Outcomes were compared among treatment groups by Cox proportional hazard models adjusting for demographic and clinical characteristics. Hazard ratios for overall survival, time to treatment failure, and time to treatment discontinuation obtained from the 3 chart reviews were synthesized in meta-analyses. RESULTS: Of 696 patients treated with everolimus as second targeted therapy, 605 patients received first targeted therapy with sunitinib/sorafenib and 91 with pazopanib. After synthesizing the hazard ratios from all studies in meta-analyses, there were no significant differences in study outcomes between patients receiving sunitinib/sorafenib versus those receiving pazopanib as first targeted therapy. CONCLUSION: There were no significant differences among outcomes while receiving second targeted therapy with everolimus for patients treated with pazopanib versus sunitinib/sorafenib as first targeted therapy.

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US.

OBJECTIVE: To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI). METHODS: A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012-January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models. RESULTS: A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR) = 1.16; 95% confidence interval [CI] = 0.73-1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p < 0.001). LIMITATIONS: Retrospective observational study design and only drug acquisition costs considered in drug costs estimates. CONCLUSIONS: Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher-by 17% per month of PFS-with axitinib than with everolimus.

Could targeting bone delay cancer progression? Potential mechanisms of action of bisphosphonates.

Although dissemination may occur early in the course of many cancers, the development of overt metastases depends upon a variety of factors inherent to the cancer cells and the tissue(s) they colonize. The time lag between initial dissemination and established metastases could be several years, during which period the bone marrow may provide an unwitting sanctuary for disseminated tumor cells (DTCs). Survival in a dormant state within the bone marrow may help DTCs weather the effects of anticancer therapies and seed posttreatment relapses. The importance of the bone marrow for facilitating DTC survival may vary depending on the type of cancer and mechanisms of tumor cell dissemination. By altering the bone microenvironment, bisphosphonates may reduce DTC viability. Moreover, some bisphosphonates have demonstrated multiple anticancer activities. These multiple mechanisms may help explain the improvement in disease outcomes with the use of zoledronic acid in malignancies like breast cancer and multiple myeloma.

Melanoma cutáneo: estudio retrospectivo de 10 años (1981-1991) / Cutaneous melanoma: 10 years (1981-1991) of retrospective study

El Melanoma cutáneo ha aumentado dramáticamente en su incidencia y pronto será uno de los tumores cutáneos más comunes en los individuos de piel blanca quienes se han expuesto al sol. Afortunadamente debido a su pigmentación característica y su localización en zonas visibles, la enfermedad usualmente puede ser diagnosticada precozmente cuando puede ser curable mediante cirugía. El conocer el estadio del tumor primario es un medio útil para pronosticar su evolución y así permitir la elaboración de un plan razonable en la estrategia de su tratamiento

Cáncer asociado a infección por el virus de inmunodeficiencia humana / Associate neoplasm to human immunodeficiency virus

En el presente estudio se trararon 30 pacientes con Sarcoma de Kaposi Epidémico (SKE), 12 con Linfomas no Hodgkin (LNH) y uno con Enfermedad de Hodgkin (EH); todos con una prueba de ELISA (+) para VIH. El tratamiento recibido fue: dosis altas de Interferon Alfa (IFN alfa) (5), dosis bajas de IFN alfa junto a AZT (8), doxorubicina (3), bleomicina (6), y poliquimioterapia (Doxorubicina, Bleomicina, vincristina) (8). Los resultados obtenidos fueron los siguientes: a) Altas dosis de IFN alfa: 3 pacientes estabilizaron su enfermedad y 2 progresaron; b) Bajas dosis de IFN alfa junto a AZT: 1 respuesta completa, 4 respuestas parciales y 3 enfermedad estable; c) Monoquimioterapia: 2 enfermedad esstable y 1 progresión (Doxorubicina), 3 enfermedad estable y 3 progresión (Bleomicina); d) Poliquimioterapia: 2 respuestas parciales y 6 enfermedades estables. Veinte pacientes ha fallecido (sobrevida 10 meses). Los 12 pacientes con LNH fueron divididos en 9 difusos y 3 primarios del SNC. El tratamiento administrado fue CHOP, m-BACOD y/o radioterapia. En los 9 pacientes con LNH difuso hubo 2 respuestas completas, 5 respuestas parciales y una enfermedad estable. El promedio de sobrevida en 7 pacientes que han fallecido fue 5 meses, los 2 pacientes que alcanzaron respuesta completa han vivido mas de 43 meses y 6 meses respectivamente. El paciente con EH recubió quimioterapia con MOPP-ABV y alcanzó una respuesta parcial la cual se mantuvo durante 20 meses. De los resultados presentados se puede concluir: 1. En pacientes sin infección por oportunista previa o coexistente y sin síntomas sistémicos, las lesiones cutáneas diseminadas se pueden tratar con dosis bajas del IFN alfa y AZT. 2. La tolerancia a dosis bajas de IFN alfa y AZT fue excelente, sin toxicidad limitante. 3. Las lesiones viscerales y lesiones cutáneas extensas se pueden tratar con poliquimioterapia (Vincristina, doxorubicina, Bleomicina). 4. No hay correlación entre los cambios en el número de células CD4, CD8 ni la razón CD4/CD8 y la respuesta del SKE al tratamiento. 5. A pesar de las respuestas obtenidas, ninguno de los tratamientos actuales modifica en forma sustancial la sobrevida global, en los pacientes con SKE. 6. En pacientes con infección por VIH los LNH tienen presentaciones clínicas agresivas y poco usuales. 7. El esquema CHOP es bien tolerado por los pacientes con LNH asociado a SIDA. 8. No hay correlación entre la respuesta clínica del LNH difuso y los niveles de células CD4, CD8 ni la razón CD4/CD8

Linfoma primario del sistema nervioso central: presentación de un caso y revisión de la literatura / Primary lymphoma of the central nervous system: report of a case and review of the literature

El Linfoma Primario del Sistema Nervioso Central (SNC) es una enfermedad rara. Constituye el 0,5% de las neoplasias cerebrales y el 1,6% de los linfomas extranodales. Ocurre con mayor frecuencia en pacientes inmunosuprimidos, particularmente aquellos sometidos a transplantes de órganos o con el síndrome de inmunodeficiencia adquirida. Se presenta con una variedad de síntomas y signos del SNC. Tiene una apariencia característica, aunque no diagnostica en la Tomografía Axial Computarizada (TAC) de cerebro. La mayoria de los casos corresponden al linfoma histiocítico difuso (LHD). La Radioterapia (Rx) ha sido la primera modalidad terapéutica, aunque no se han obtenido remisiones duraderas, la sobrevida es de 47% en el primer año y 16% en el segundo. Recientemente se han popuesto esquemas de tratamiento con quimioterapia y modificación de la barrera hematoencefálica con aparente mejor respuesta. Se presenta una paciente femenina de 56 años sin antecedentes de inmunosupresión, con episodios convulsivos de dos meses de evolución. La TAC cerebral mostraba una lesión isodensa temporoparietal izquierda que se intensificaba con el contraste endovenoso. Fue intervenida practicándose exceresis de la lesión, siendo el diagnóstico histológico LHD. No existía evidencia clínica ni paraclínica de enfermedad fuera del SNC. Recibió Rx en todo el cerebro con 4000 rad, siendo hasta el momento la evolución satisfactoria

Naproxeno y fiebre neoplásica: un estudio doble ciego / Naproxen and neoplasic fever: a double blind study

La fiebre neoplásica es una situación común en pacientes con cáncer. Se llevó a cabo un estudio prospectivo, controlado con placebo, randomizado y doble ciego con el propósito de evaluar la respuesta de la fiebre neoplásica a una dosis adecuada de Naproxeno. Fueron evaluados 14 pacientes con diagnóstico de Cáncer, siendo más frecuentes las hemopatías malignas (6 Linfomas No-Hosgkin, 3 Enfermedad de Hodgkin y 1 Leucemia Mieloide Crónica). Ningún paciente presentó neutropenia severa, ni modificó su curva térmica con el uso de antibióticos. La totalidad de los pacientes presentó una lisis total de la fiebre al recibir al Naproxeno, ocurriendo esto es un tiempo menor a 6 horas en el 64 por ciento de los pacientes. El promedio de la temperatura de los pacientes con el Naproxeno fue estadísticamente inferior al promedio con el Placebo. En conclusión el Naproxeno puede ser una droga útil en el tratamiento sintomático de la fiebre neoplásica

Cáncer de mama: fatiga como indicador de calidad de vida / Neoplasm of breast: fatigue like life quality indicator

El tratamiento sistémico indicado para el cáncer de mama está asociado con varios síntomas. La fatiga relacionada con cáncer es uno de los más frecuentes. Evaluar la relación de fatiga relacionada con cáncer con distintas variables, evaluar su variación durante el ciclo de quimioterapia y formular una encuesta válida para el estudio de la fatiga relacionada con cáncer. Se formuló una encuesta para evaluar la intensidad de la fatiga relacionada con cáncer, durante los 21 días del ciclo de la quimioterapia. Se encuestaron 51 pacientes, en tratamiento con diferentes esquemas de quimioterapia. El mayor número de eventos de fatiga importante fue entre el día 3 y el día 8 del ciclo. La aparición de fatiga se asoció de una manera significativa, con el esquema de tratamiento y el número de ciclos cumplidos. El esquema que produjo mayor índice de fatiga severa fue: Ciclofostamida-Metotrexate-5-Fluoracilo. La encuesta para fatiga relacionada con cáncer resultó fiable. Conclusión: se identificaron variaciones de intensidad de la fatiga a lo largo del ciclo y diferencias entre los distintos esquemas de quimioterapia

Cáncer de mama y embarazo en el Instituto Oncológico "Luis Razetti" / Breast neoplasm and pregnancy in the Instituto Oncologico \"Luis Razetti\"

Se revisaron retrospectivamente 16 historias de pacientes con cáncer (Ca) de mama asociado al embarazo tratadas en el Instituto Oncológico "Luis Razetti" (IOLR) entre 1985 y 1994. La edad promedio de las pacientes fue de 36 años, con una edad gestacional promedio de 11 semanas y 5 días. Los estadios más frecuentes fueron IIIb (37,5 por ciento) y IIb (31,1 por ciento). Desde el punto de vista quirúrgico 11 pacientes (68,8 por ciento) fueron tratadas con mastectomía radical modificada y 1 paciente con cirugía preservadora. El 75 por ciento de las pacientes recibió quimioterapia, siendo los esquemas más utilizados CAF (50 por ciento) y CMF (33,4 por ciento). Los receptores de estrógeno fueron negativos en 8 pacientes (50 por ciento) y positivos en 2 (12,5 por ciento). La conducta obstétrica fue parto espontáneo en 9 pacientes, aborto terapéutico en 6 pacientes y cesárea en 1 paciente. Con relación al seguimiento 9 pacientes (56,3 por ciento) precentaron recaídas, siendo las ubicaciones más frecuentes hueso y pulmón, el 25 por ciento de las pacientes se encuentran vivas sin enfermedad, 31,3 por ciento muertas y 12,5 por ciento perdidas de control. En conclusión el pronóstico de las pacientes de Ca. de mama durante el embaraza semejante al de pacientes no embarazadas de la misma edad y estadio de la enfermedad, y en los casos revisados no se encontró evidencia de anomalías en los productos de gestación que recibieron quimioterapia in útero

Miositis osificante asociada a lupus eritematoso sistemico: presentación de un caso / Myositis ossificans associated with sistemic lupus erythematosus: a case report

Se define Miositis Osificante a la formación de tejido óseo y cartilaginoso, no neoplásico, en los tejidos adyacentes a los músculos y en proximidad, cuya manifestación clínica más evidente es dolor, inflamacion y formación de tumor relacionado principalmente con traumatismo y asociado raramente con enfermedad del tejido conectivo. Se presenta un caso clínico de Miositis Osificante asociado a Lupus Eritematoso Sistémico en una paciente de 20 años de edad tratada en el Servicio de Medicina 2 del Hospital Vargas de Caracas