Evaluación del tratamiento de linfoma de Hodgkin con esquema ABVD en Chile / Treatment of Hodgkin lymphoma: analysis of 915 patients

Background: Hodgkin lymphoma has a high rate of curability, even in advanced stages. Aim: To assess the results of Hodgkin lymphoma treatment using the ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy regimen. Material and Methods: Analysis of a database held by the Chilean Ministry of Health, including all patients treated at accredited cancer treatment centers. Results: Data for 915 patients, median age 35 years (range 15-86 years) and followed for a median of 97 months (range 1-347 months) were analyzed. Forty-one percent had localized disease. Overall survival at five years for localized and advanced stages was 92% and 74%, respectively. The figures for progression free survival were 87% and 64%, respectively. Patients with relapse who received autologous stem cell transplantation (ASCT) had a five year overall survival of 92%, compared to 64% among those who did not undergo this procedure (p < 0.01). The Guarantees in Health Program set up by the Ministry of Health, was associated with earlier stage disease at diagnosis. Conclusions: The ABVD regimen achieves high rates of cure in localized stages of the disease but the results in advanced stages are not optimal. ASCT significantly improves survival in patients with relapse. The Guarantees in Health Program is associated with earlier diagnosis of the disease.

Macroglobulinemia de Waldenström: experiencia de 15 años en el Hospital del Salvador, Santiago, Chile / Waldenström macroglobulinemia: experience in 31 patients

Background: Waldenström macroglobulinemia (WM) is an uncommon indolent B-cell lymphoma, due to the proliferation of lymphoplasmacytic cells, and secretion of a monoclonal IgM protein. Aim: To evaluate the clinical characteristics, management and results of treatment of patients with WM at a public hospital in Chile. Patients and Methods: Review of medical records of 31 patients aged 43 to 85 years (16 males) with WM diagnosed between 2002 and 2017. Clinical features and survival were recorded. Results: All patients had bone marrow compromise, and 31%, extranodal involvement. According to the International Prognostic Score System for WM (IPSSWM) 16, 58 and 26% were at low, intermediate and high risk, respectively. Twenty-five patients (81%) were treated, 32% with plasmapheresis and 36% with rituximab. Four cases (16%) achieved complete remission. Median follow up was 35 months (range 6-159). Estimated overall survival (OS) at 5 and 10 years was 74% and 53%, respectively. According to IPSSWM, the estimated five-year OS was 80, 92 and 39%, for low, intermediate and high-risk patients, respectively. Conclusions: OS was similar to that reported abroad, except for low risk patients, probably due to the low number of cases and short follow up. An improved survival should be expected with the routine use of immunochemotherapy.

Perception of women with breast cancer undergoing chemotherapy: a comprehensive analysis / Percepción de mujeres con cáncer de mama en quimioterapia: un análisis exhaustivo / Percepção de mulheres com câncer de mama em quimioterapia: uma análise compreensiva

ABSTRACT Objective: To comprehensively analyze the perception of women with breast cancer on the experience of undergoing chemotherapy. Method: This was a qualitative, descriptive, phenomenological study, supported by the Merleau-Ponty philosophy. It was conducted in a chemotherapy outpatient clinic with 20 participants who completed a phenomenological interview. Results: The phenomenological data analysis demonstrated that the perception of women about the experience of chemotherapy is about change, not only of the physical body, but of their identity, and that it considers existential aspects. Three categories emerged from the experience of alopecia, fatigue, and spirituality, respectively: the body itself, the current and habitual body, and transcendence. Final considerations: Bodily changes, and the existential implications perceived by the women in this study, analyzed from the Merleau-Ponty perspective, makes it possible to consider body concept, and provides support for humanized care based on singularity and the socio-cultural context.

RESUMEN Objetivo: Analizar exhaustivamente la percepción de las mujeres con cáncer de mama sobre la experiencia de la quimioterapia. Método: Este fue un estudio cualitativo, descriptivo, fenomenológico, respaldado por la filosofía Merleau-Ponty realizada en una clínica ambulatoria de quimioterapia con 20 participantes que se sometieron a una entrevista fenomenológica. Resultados: El análisis fenomenológico de los datos demostró que la percepción de las mujeres sobre la experiencia de la quimioterapia tiene que ver con el cambio, no solo del cuerpo físico, sino de la identidad y el alcance de los aspectos existenciales. De la alopecia, fatiga y espiritualidad emergieron tres categorías respectivamente: el cuerpo mismo, el cuerpo actual y habitual y la trascendencia. Consideraciones finales: El cambio del cuerpo y sus implicaciones existenciales percibidas por las mujeres en este estudio, y analizadas bajo la perspectiva de Merleau-Pontyana, permiten cubrir la concepción del cuerpo y proporcionar subsidios para el cuidado humanizado basado en la singularidad y el contexto sociocultural.

RESUMO Objetivo: Analisar compreensivamente a percepção de mulheres com câncer de mama sobre a vivência da quimioterapia. Método: Trata-se de um estudo de natureza qualitativa, descritivo, do tipo fenomenológico, respaldado na filosofia de Merleau-Ponty. Foi realizado em um ambulatório de quimioterapia e contou com 20 participantes que foram submetidas a entrevista fenomenológica. Resultados: A partir da análise fenomenológica dos dados, compreendeu-se que a percepção das mulheres sobre a vivência da quimioterapia é de mudança, não só de corpo físico, mas de identidade e alcança aspectos existenciais. A partir da vivência da alopecia, fadiga e espiritualidade emergiram três categorias respectivamente: o corpo próprio, o corpo atual e habitual e a transcendência. Considerações finais: A mudança de corpo e suas implicações existenciais percebidas pelas mulheres no estudo, analisadas sob a ótica Merleau-Pontyana, possibilitam abranger a concepção de corpo, fornecendo subsídios para o cuidado humanizado a partir da singularidade e do contexto sociocultural.

Efecto de la metformina en la etapa de inducción en pacientes con leucemia aguda linfoblástica y su impacto clínico en la supervivencia / Effect of metformin added to chemotherapy on the survival of patients with acute lymphoblastic leukemia

Background: Metformin has antineoplastic and cancer protective effects in vitro, sensitizing leukemia cells to chemotherapeutic agents, inducing apoptosis and cell cycle arrest. Aim: To assess the effect of metformin on the induction stage in patients with ALL and its impact on overall survival and relapse. Material and Methods. We included 123 patients treated with metformin and without metformin. The dose used was 850 mg PO at 8 h intervals. The survival analysis was used by Kaplan-Meier method, the difference between the distinct groups was performed using the log Rank test. Results. The overall survival at a median follow up of 700 days of follow-up was 43%, with a disease-free survival of 47%. Regarding the treatment groups, patients with metformin had a lower rate of relapse compared to the group receiving only chemotherapy (6.5% vs 17.1%, p = 0.006). Conclusions. The addition of metformin to the conventional treatment of ALL was associated with an improvement in survival, this association being independent of the type of biological risk at diagnosis.

The clinical efficacy and safety of paclitaxel combined with avastin for NSCLC patients diagnosed with malignant pleural effusion

Summary Objective: The current study aimed to investigate the clinical efficacy of paclitaxel combined with avastin for non-small cell lung cancer (NSCLC) patients diagnosed with malignant pleural effusion (MPE). Method: Total of 33 patients diagnosed with NSCLC as well as malignant pleural effusion were included. All of them received paclitaxel (175 mg/m2) and avastin (5 mg/kg). Clinical efficacy was evaluated using the total response rate, overall survival, progression-free survival and changes in MPE volume. Adverse events and rates of toxicities were examined as well. Results: The total response rate reached 77% while the overall survival and the median progression-free survival were respectively 22.2 months and 8.4 months. Toxicities of grade 3-4 consisted of neutropenia in 57% of patients, anemia in 17% of them, febrile neutropenia in 11%, as well as anorexia in 7%. No treatment-correlated deaths were found. Conclusion: Paclitaxel combined with avastin decreased MPE volume and increased survival rate of NSCLC patients via inhibiting vascular endothelial growth factor expression.

Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases / Tratamento bem-sucedido de leucemia mieloide aguda recorrente após transplante com duplicação interna em tandem FLT3 usando combinação de indução por quimioterapia, infusão de linfócitos de doador, soferanib e azacitidina. Relato de três casos

ABSTRACT Acute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.

RESUMO A leucemia mieloide aguda é uma doença neoplásica de células-tronco hematopoiéticas com alta morbimortalidade. A presença de mutações de duplicação em tandem de FLT3 leva a altas taxas de recorrência e a menor sobrevida global. Os pacientes com duplicação em tandem de FLT3 são normalmente tratados com transplante de células-tronco hematopoiéticas na primeira remissão completa. No entanto, a incidência de recidiva pós-transplante é considerável neste grupo de pacientes, e a conduta, nestes casos, é um desafio. O relato descreve os resultados do tratamento de pacientes com leucemia mieloide aguda positiva e duplicação em tandem de FLT3 que recidivaram depois do transplante alogênico de células-tronco hematopoiéticas e que foram tratados com combinação de quimioterapia de reindução, infusão de linfócitos de doador, sorafenib e azacitidina. São descritos três casos, e todos os pacientes apresentaram remissão completa prolongada com a terapia combinada. A combinação de quimioterapia de indução, seguida de infusão de linfócitos do doador, e a manutenção com azacitidina e sorafenib podem ser abordagens eficazes no tratamento da recorrência pós-transplante em pacientes com leucemia mieloide aguda e duplicação em tandem de FLT3. Essa estratégia deve ser mais explorada no contexto de ensaios clínicos.

Plasmocitoma extramedular: una rara causa de masa mediastínica / Extramedullary mediastinal plasmacytoma: report of one case

Solitary extramedullary plasmacytomas represent 3% of plasma cell neoplasms. Their most common locations are the upper gastrointestinal and respiratory tract. We report a 70-year-old male presenting with progressive dyspnea and cough. A chest radiography showed widened mediastinum. Chest computed tomography showed a mediastinal mass. A bronchoscopy showed an extrinsic compression and complete occlusion of the primary bronchus. A self-expandable prosthesis was installed in left bronchus. A population of plasmacytoid cells was evidenced in the mass biopsy. Immunohistochemistry revealed CD20+ and CD138+. These tumor cells stained positively for lambda light chains, but negatively for kappa chains. Therefore an extramedullary plasmacytoma was diagnosed. A multiple myeloma was discarded with a normal blood count, serum calcium and creatinine levels. Serum protein electrophoresis had a monoclonal spike, serum IgG was 1963 mg/dl. Bone marrow aspiration had 1% of plasma cells. Bone x-rays were normal. Computed tomographies of the neck, thorax, abdomen and pelvis ruled out other plasmacytomas. Eight cycles of chemotherapy with thalidomide, melphalan and prednisone were indicated, obtaining complete remission of the tumor. The review of the literature shows that mediastinal extramedullary plasmacytomas are extremely rare. They generally appear in men aged between 50 and 60 years. The treatment of choice is radiotherapy, but given the location in the present case, chemotherapy was considered the best option. Recurrence is approximately 10 to 30% and 10% of patients progress to myeloma, thus requiring close monitoring.

Tres casos de mieloma múltiple de novo después de trasplante renal / Three cases of de novo multiple myeloma after kidney transplantation

RESUMEN La enfermedad renal asociada a cadenas ligeras es frecuente en el contexto de las gammapatías monoclonales, afecta los glomérulos o los túbulos renales, y su causa más común es el mieloma múltiple. Puede desarrollarse después de un trasplante renal por recurrencia de un mieloma múltiple ya existente, o puede ser de diagnóstico nuevo y presentarse con deterioro de la función renal y proteinuria. Siempre se requiere una biopsia renal para confirmar el diagnóstico.

ABSTRACT Light chain-associated kidney compromise is frequent in patients with monoclonal gammopathies; it affects the glomeruli or the tubules, and its most common cause is multiple myeloma. It may develop after a kidney transplant due to recurrence of a preexisting multiple myeloma or it can be a de novo disease manifesting as graft dysfunction and proteinuria. A kidney biopsy is always necessary to confirm the diagnosis.

Chemotherapy for advanced non-small cell lung cancer in the elderly population

ABSTRACT BACKGROUND: Approximately 50% of patients with newly diagnosed non-small cell lung cancer (NSCLC) are over 70 years of age at diagnosis. Despite this fact, these patients are underrepresented in randomized controlled trials (RCTs). As a consequence, the most appropriate regimens for these patients are controversial, and the role of single-agent or combination therapy is unclear. In this setting, a critical systematic review of RCTs in this group of patients is warranted. OBJECTIVES: To assess the effectiveness and safety of different cytotoxic chemotherapy regimens for previously untreated elderly patients with advanced (stage IIIB and IV) NSCLC. To also assess the impact of cytotoxic chemotherapy on quality of life. METHODS: Search methods: We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10), MEDLINE (1966 to 31 October 2014), EMBASE (1974 to 31 October 2014), and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to 31 October 2014). In addition, we handsearched the proceedings of major conferences, reference lists from relevant resources, and the ClinicalTrial.gov database. Selection criteria: We included only RCTs that compared non-platinum single-agent therapy versus non-platinum combination therapy, or non-platinum therapy versus platinum combination therapy in patients over 70 years of age with advanced NSCLC. We allowed inclusion of RCTs specifically designed for the elderly population and those designed for elderly subgroup analyses. Data collection and analysis: Two review authors independently assessed search results, and a third review author resolved disagreements. We analyzed the following endpoints: overall survival (OS), one-year survival rate (1yOS), progression-free survival (PFS), objective response rate (ORR), major adverse events, and quality of life (QoL). MAIN RESULTS: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. AUTHORS' CONCLUSIONS: In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making

Her2 expression as a prognostic factor in metastatic gastric cancer

ABSTRACT Background - Human epidermal growth factor receptor 2 (EGFR2/HER2/ErbB2) is a transmembrane receptor that stimulates cell proliferation when activated. The correlation of HER2 expression with prognosis has been studied in many cancer types. However, its relationship with survival of patients with metastatic gastric cancer remains unknown. Moreover, there is a lack of information on this issue in a Brazilian population. Objective - To assess the proportion of patients whose tumor cells express HER2 and correlate this with clinical characteristics as well as treatment outcomes. Methods - This was a retrospective study. We included adult patients with metastatic gastric cancer treated at an University Hospital between 2011 and 2015. Patients did not receive anti-HER2 therapy. Receptor expression was evaluated by immunohistochemistry. Survival risk factors were assessed individually with univariate Cox regression, and a P value <0.05 was considered statistically significant. Results - Forty-nine patients were included in this study. However, only 32 had samples assessed for HER2 expression. Five (16%) patients were positive. Among HER2-negative patients, the average age was 54 years, 44% received a treatment protocol with three drugs, 70% had a performance status score 0-1, and 41% had well or moderately differentiated histology. Among HER2-positive patients, the average age was 58 years, 40% received three drugs, 100% had a performance status score 0-1, and 67% had well or moderately differentiated histology. Response rate was evaluated in 28 cases, and there was no difference between the groups (HER2-negative 52% vs. HER2-positive 40%; P=0.62). Survival outcomes were numerically worse among HER2-positive patients. Median progression-free survival was 8.3 months for HER2-positive patients and 10.6 months for HER2-negative patients (HR 1.61, 95% CI: 0.59-4.38); median overall survival was 14.8 months and 16.9 months for HER2-positive and HER2-negative patients, respectively (HR 1.52, 95% CI: 0.50-4.66). Conclusion - HER2 overexpression in metastatic gastric cancer patients may be a predictor of poor prognosis and further validation is warranted.

RESUMO Contexto - O receptor 2 do fator de crescimento epidermal humano (EGFR2/HER2/ErbB2) é um receptor transmembrana que estimula a proliferação celular quando ativado. A expressão de HER2 foi estudada em diversas neoplasias, como câncer gástrico. No entanto, sua relação com a sobrevida dos pacientes com câncer gástrico metastático permanece desconhecida. Além disso, há falta de informação sobre este assunto na população brasileira. Objetivo - Avaliar a proporção de pacientes cujas células tumorais expressam HER2 e correlacionar essa característica com aspectos clínicos e também com os desfechos do tratamento. Métodos - Este é um estudo retrospectivo. Foram incluídos pacientes adultos com câncer gástrico metastático tratados em um Hospital Geral Universitário entre 2011 e 2015. Nenhum paciente recebeu terapia anti-HER2. A expressão do receptor foi avaliada por imuno-histoquímica. Fatores de risco para a sobrevida foram avaliados com regressão de Cox univariada e valor P<0,05 foi considerado estatisticamente significativo. Resultados - Quarenta e nove pacientes foram incluídos neste estudo. No entanto, 32 tiveram amostras avaliadas para expressão de HER2. Cinco (16%) pacientes foram positivos. Entre os pacientes HER2 negativos: a idade média foi de 54 anos, 44% receberam um protocolo com três drogas, 70% apresentavam um score de status performance 0-1, 41% tinham histologia bem ou moderada diferenciada. Entre os pacientes HER2 positivos: a média de idade foi de 58 anos, 40% receberam três drogas, 100% apresentavam um score de status performance de 0-1, 67% tinham histologia bem ou moderada diferenciada. A taxa de resposta foi avaliada em 28 casos e não houve diferença entre os grupos (HER2 negativo 52% e HER2 positivo de 40%; P=0,62). A sobrevida foi menor entre pacientes HER2 positivos. As medianas de Sobrevida Livre de Progressão foram 8,3 meses e 10,6 meses, respectivamente (HR 1,61; IC 95%: 0,59-4,38). As medianas de Sobrevida Global foram 14,8 meses e 16,9 meses, respectivamente (HR 1,52; IC 95%: 0,50-4,66). Conclusão - A expressão tumoral de HER2 pode ser um fator de pior prognóstico para pacientes portadores de câncer gástrico metastático e uma validação futura desses achados se faz necessária.

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range.

Chemotherapy and prognosis in advanced thymic carcinoma patients

OBJECTIVE: The role of chemotherapy in treating advanced thymic carcinoma is unclear. The purpose of the current study was to investigate the efficacy of chemotherapy and the prognostic factors for patients with advanced thymic carcinoma. METHODS: A retrospective review of the medical records of 86 patients treated with chemotherapy for advanced thymic carcinoma was conducted between 2000 and 2012 at our institution. The clinical characteristics, chemotherapy regimens and prognostic factors were analyzed. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazard model was used for multivariate analysis. RESULTS: Of the 86 patients, 56 were male and 30 were female. The median survival time was 24.5 months. For the first-line chemotherapy treatment, the objective response rate was 47.7% and the disease control rate was 80.2%. The median progression-free survival for all patients was 6.5 months for first-line chemotherapy. No significant differences in progression-free survival were observed among the different chemotherapy regimens. Multivariate analyses revealed that the prognostic factors for overall survival included performance status (p=0.043), histology grade (p=0.048), and liver metastasis (p=0.047). CONCLUSION: Our results suggest that there is no difference in efficacy between multiagent and doublet regimens. The prognosis of patients with advanced thymic carcinoma can be predicted based on histological grade, liver metastasis and performance status.

Changes in circulating endothelial progenitor cells predict responses of multiple myeloma patients to treatment with bortezomib and dexamethasone

Four cycles of chemotherapy are required to assess responses of multiple myeloma (MM) patients. We investigated whether circulating endothelial progenitor cells (cEPCs) could be a biomarker for predicting patient response in the first cycle of chemotherapy with bortezomib and dexamethasone, so patients might avoid ineffective and costly treatments and reduce exposure to unwanted side effects. We measured cEPCs and stromal cell-derived factor-1α (SDF-1α) in 46 MM patients in the first cycle of treatment with bortezomib and dexamethasone, and investigated clinical relevance based on patient response after four 21-day cycles. The mononuclear cell fraction was analyzed for cEPC by FACS analysis, and SDF-1α was analyzed by ELISA. The study population was divided into 3 groups according to the response to chemotherapy: good responders (n=16), common responders (n=12), and non-responders (n=18). There were no significant differences among these groups at baseline day 1 (P>0.05). cEPC levels decreased slightly at day 21 (8.2±3.3 cEPCs/μL) vs day 1 (8.4±2.9 cEPCs/μL) in good responders (P>0.05). In contrast, cEPC levels increased significantly in the other two groups (P<0.05). SDF-1α changes were closely related to changes in cEPCs. These findings indicate that change in cEPCs at day 21 in the first cycle might be considered a noninvasive biomarker for predicting a later response, and extent of change could help decide whether to continue this costly chemotherapy. cEPCs and the SDF-1α/CXCR4 axis are potential therapeutic targets for improved response and outcomes in MM patients.

Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

Agregação familiar da doença renal crônica secundária à hipertensão arterial ou diabetes mellitus: estudo caso-controle / Family clustering of secondary chronic kidney disease with hypertension or diabetes mellitus. A case-control study

No Brasil, a hipertensão e o diabetes mellitus tipo 2 são responsáveis por 60% dos casos de doença renal crônica terminal em terapia renal substitutiva. Estudos americanos identificaram agregação familiar da doença renal crônica, predominante em afrodescendentes. Um único estudo brasileiro observou agregação familiar entre portadores de doença renal crônica quando comparados a indivíduos internados com função renal normal. O objetivo deste artigo é avaliar se existe agregação familiar da doença renal crônica em familiares de indivíduos em terapia renal substitutiva causada por hipertensão e/ou diabetes mellitus. Estudo caso-controle tendo como casos 336 pacientes em terapia renal substitutiva portadores de diabetes mellitus ou hipertensão há pelo menos 5 anos e controles amostra pareada de indivíduos com hipertensão ou diabetes mellitus e função renal normal (n = 389). Os indivíduos em terapia renal substitutiva (casos) apresentaram razão de chance de 2,35 (IC95% 1,42-3,89; p < 0,001) versus controles de terem familiares com doença renal crônica terminal, independente da raça ou doença de base. Existe agregação familiar da doença renal crônica na amostra estudada e esta predisposição independe da raça e da doença de base (hipertensão ou diabetes mellitus).

In Brazil hypertension and type 2 diabetes mellitus are responsible for 60% of cases of end-stage renal disease in renal replacement therapy. In the United States studies have identified family clustering of chronic kidney disease, predominantly in African-Americans. A single Brazilian study observed family clustering among patients with chronic kidney disease when compared with hospitalized patients with normal renal function. This article aims to assess whether there is family clustering of chronic kidney disease in relatives of individuals in renal replacement therapy caused by hypertension and/or diabetes mellitus. A case-control study with 336 patients in renal replacement therapy with diabetes mellitus or hypertension for at least 5 years (cases) and a control matched sample group of individuals with hypertension or diabetes mellitus and normal renal function (n = 389). Individuals in renal replacement therapy (cases) had a ratio of 2.35 (95% CI 1.42-3.89, p < 0.001) versus the control group in having relatives with chronic renal disease, irrespective of race or causative illness. There is family clustering of chronic kidney disease in the sample studied, and this predisposition is irrespective of race and underlying disease (hypertension or diabetes mellitus).

Efeito da revascularização renal sobre a evolução da disfunção renal na nefropatia isquêmica aterosclerótica / Effect of renal revascularization on the development of renal dysfunction in atherosclerotic ischemic nephropathy

A doença renal crônica (DRC) é caracterizada por uma perda progressiva da função renal e suas principais causas são hipertensão arterial (HA) e diabete melito. Entre as causas de HA, podemos destacar a doença renal aterosclerótica (DRA). O desenvolvimento de DRC nos pacientes com DRA parece ser decorrente não apenas do acometimento das artérias renais principais, mas também da microcirculação renal, o que pode justificar o fato de o sucesso do procedimento não garantir uma melhora da evolução da DRC. Até o presente momento, não existe evidência de benefício da angioplastia em relação ao tratamento clínico exclusivo nos pacientes com DRA. O presente trabalho analisa os estudos mais significantes sobre os desfechos renais em pacientes portadores de DRA submetidos à revascularização ou ao tratamento clínico exclusivo.

Chronic kidney disease (CKD) is characterized by a progressive loss of renal function and its main causes are hypertension and diabetes mellitus. Among the causes of hypertension is atherosclerotic renal disease (ARD). The development of CKD in patients with ARD appears to be due not only to the involvement of the main renal arteries, but also of the renal microcirculation, which may explain the fact that the success of the procedure does not guarantee an improvement in the progression of CKD. To date there is no evidence of benefit of angioplasty compared to medical treatment alone in patients with ARD. The present paper analyzes the most significant studies on renal outcomes in patients with ARD undergoing revascularization or medical treatment alone.

Quality of life, clinical characteristics and treatment adherence of people living with HIV/AIDS / Qualidade de vida, características clínicas e adesão ao tratamento de pessoas vivendo com HIV/AIDS / Calidad de vida, características clínicas y adhesión al tratamiento de personas viviendo con VIH/Sida

OBJECTIVES: to assess the quality of life of people living with HIV/AIDS and verify its association with clinical characteristics and treatment adherence. METHOD: cross-sectional study conducted in a hospital in the state of Paraíba, Brazil. A questionnaire was used to collect socio-demographic and clinical data. The quality of life scale proposed by the World Health Organization and a questionnaire to measure treatment adherence were used. RESULTS: of the 314 interviewees, 190 (60.5%) were male, aged 43 years on average, 121 (38.5%) had attended up to five years of schooling, 108 (34.4%) received up to two times the minimum wage, and 112 (35.7%) were on sick leave. In regard to clinical variables, individuals with an undetectable viral load scored higher in all the domains concerning quality of life, with statistically significant differences in three domains. Regarding treatment adherence, 235 (73.8%) presented poor adherence and those who strictly adhered to treatment obtained better scores in quality of life. The results show that quality of life is better among individuals adherent to ART. Supporting people to adhere to the antiretroviral treatment should be a persistent task of healthcare workers and other people participating in the treatment, such as family members and friends. .

OBJETIVOS: avaliar a qualidade de vida das pessoas vivendo com o vírus da imunodeficiência humana/síndrome da imunodeficiência adquirida e suas associações com características clínicas e adesão ao tratamento. MÉTODO: estudo transversal, realizado em um hospital do Estado da Paraíba. Utilizou-se questionário para caracterização sociodemográfica e clínica, escala de qualidade de vida (proposta pela Organização Mundial da Saúde) e escala de adesão ao tratamento (Questionário para Avaliação da Adesão ao Tratamento Antirretroviral). RESULTADOS: dos 314 entrevistados, 190 (60,5%) eram do sexo masculino, idade média de 43 anos, 121(38,5%) contavam com até cinco anos de estudo, 108 (34,4%) recebiam até dois salários-mínimos e 112 (35,7%) estavam afastados das atividades laborais. Quanto às variáveis clínicas, identificou-se que os indivíduos com carga viral indetectável apresentaram maiores escores em todos os domínios de qualidade de vida, com diferença estatisticamente significante em três domínios. Sobre a adesão ao tratamento, 235 (73,8%) apresentaram adesão insuficiente, os que apresentaram adesão estrita obtiveram melhores escores de qualidade de vida. Os resultados mostraram que a qualidade de vida é melhor para os aderentes ao tratamento antirretroviral. Apoiar as pessoas em tratamento para melhorar a adesão aos antirretrovirais deve ser tarefa constante dos profissionais de saúde e de outras pessoas que participam do tratamento, como familiares e amigos. .

OBJETIVOS: evaluar la calidad de vida de las personas viviendo con VIH/Sida y sus asociaciones con características clínicas y adhesión al tratamiento. MÉTODO: estudio transversal, realizado en un hospital del estado de Paraíba. Se utilizó un cuestionario para caracterización sociodemográfica y clínica, la Escala de Calidad de Vida (propuesta por la Organización Mundial de la Salud) y la Escala de Adhesión al Tratamiento (Cuestionario para Evaluación de la Adhesión al Tratamiento Antirretroviral). RESULTADOS: de los 314 entrevistados, 190 (60,5%) eran del sexo masculino, edad promedio de 43 años, 121(38,5%) contaban con hasta cinco años de estudio, 108 (34,4%) recibían hasta dos salarios mínimos y 112 (35,7%) no realizaban actividades laborales. En cuanto a las variables clínicas, se identificó que los individuos con carga viral indetectable presentaron mayores puntajes en todos los dominios de calidad de vida, con diferencia estadísticamente significativa en tres dominios. Sobre la adhesión al tratamiento, 235 (73,8%) presentaron adhesión insuficiente, los que presentaron adhesión estricta obtuvieron mejores puntajes de calidad de vida. Los resultados mostraron que la calidad de vida es mejor para los adherentes a la TARV. Apoyar a personas en tratamiento para mejorar la adhesión a los antirretrovirales debe ser una tarea constante de los profesionales de la salud y de otras personas que participan del tratamiento, como familiares y amigos. .

Qualidade de vida em mulheres no climatério atendidas na Atenção Primária / Quality of life of postmenopausal women attended at Primary Health Care / Calidad de vida de las mujeres en climaterio tratadas en la Atención Primaria

A vivência do climatério está cada vez mais presente, e demanda estratégias que melhorem a qualidade de vida das mulheres nesse período. A pesquisa objetivou avaliar a qualidade de vida de mulheres na fase do climatério, com ou sem uso da terapia de reposição hormonal (TRH). Estudo epidemiológico longitudinal, com amostra de 99 mulheres para cada grupo. Avaliaram-se as características sociodemográficas, clínicas e comportamentais. Foram aplicados à amostra a Menopause Rating Scale (MRS) e o Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Utilizaram-se os testes t de student, Qui-quadrado e Tukey. As usuárias de TRH apresentaram média etária de 50,76 ± 3,63 anos, e as não usuárias de 48,95 ± 6,27anos (p=0,01). Relataram maior frequência de sintomas climatéricos de intensidade leve a moderada. Os aspectos sociais apresentaram escore abaixo de 50 para os dois grupos. Houve diferenças entre os grupos em relação aos componentes do SF-36 e MRS para estado geral de saúde, capacidade funcional, menor capacidade, depressão, insônia e fenômenos vasomotores.

The experience of menopause is increasingly present, and demand strategies to improve the quality of life of women during this period. This research aimed to evaluate the quality of life for women in the climacteric phase, with or without the use of hormone replacement therapy (HRT). This is a longitudinal epidemiological study of a sample of 99 women per group. It was evaluated the sociodemographic, clinical and behavioral characteristics. It was used the Menopause Rating Scale (MRS) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). For data analysis, it was used the Student t test, chi-square and Tukey. HRT users had an average age of 50.76 ± 3.63 years, and nonusers of 48.95 ± 6,27anos (p = 0.01). It was identified a higher frequency of moderate climacteric symptoms of mild intensity. The social aspects evidenced scores below 50 for the two groups. There were differences between groups with respect to the components of the SF-36 and MRS to general health, functional capacity, lower capacity, depression, insomnia and vasomotor phenomena.

La experiencia de la menopausia es cada vez más presente, demandando estrategias para mejorar la calidad de vida de las mujeres durante este periodo. Esa investigación tuvo como objetivo evaluar la calidad de vida de las mujeres en la fase climatérica, con o sin el uso de la terapia de reemplazo hormonal (TRH). Trata-se dé un estudio epidemiológico longitudinal, con una muestra de 99 mujeres por grupo. Fueran evaluadas las características sociodemográficas, clínicas y de comportamiento. Fueran aplicados a la muestra el Menopause Rating Scale (MRS) e el Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Utilizaran-se los testes t de Student, Qui-quadrado e Tukey. Las usuarias de TRH tenían una edad media de 50,76 ± 3,63 años, y las no usuarias de 48,95 ± 6,27anos (p = 0,01). Fue reportada una mayor frecuencia de síntomas climatéricos intensidad leve o moderada. Los aspectos sociales tuvieran puntuaciones por debajo de 50 para los dos grupos. Hubo diferencias entre los grupos con respecto a los componentes del SF-36 y el MRS para la salud en general, la capacidad funcional, la capacidad más baja, la depresión, el insomnio y los fenómenos vasomotores.

ErbB2+ metastatic breast cancer treatment after progression on trastuzumab: a cost-effectiveness analysis for a developing country / Tratamientos para cáncer de seno metastásico ErbB2+ en progresión Post-Trastuzumab: Análisis de costo-efectividad para un país en vía de desarrollo

Objective Breast cancer (BC) and metastatic breast cancer (MBC) are significant causes of deaths amongst women worldwide, including developing countries. The cost of treatment in the latter is even more of an issue than in higher income countries. ErbB2 overexpression is a marker of poor prognosis and the goal for targeted therapy. This study was aimed at evaluating the cost-effectiveness in Colombia of ErbB2+ MBC treatment after progression on trastuzumab. Methods A decision analytic model was constructed for evaluating such treatment in a hypothetical cohort of ErbB2+MBC patients who progressed after a first scheme involving trastuzumab. The alternatives compared were lapatinib+capecitabine (L+C), and trastuzumab+a chemotherapy agent (capecitabine, vinorelbine or a taxane). Markov models were used for calculating progression-free time and the associated costs. Effectiveness estimators for such therapy were identified from primary studies; all direct medical costs based on national fees-guidelines were included. Sensitivity was analyzed and acceptability curves estimated. A 3 % discount rate and third-payer perspective were used within a 5-year horizon. Results L+C dominated its comparators. Its cost-effectiveness ratio was COP $49,725,045 per progression-free year. The factors most influencing the results were the alternatives' hazard ratios and the cost of trastuzumab. Conclusion Lapatinib was cost-effective compared to its alternatives for treating MBC after progression on trastuzumab using a Colombian decision analytic model.

Objetivo El cáncer de seno (CS) y cáncer de seno metastásico (CSM) son importantes causas de muerte entre las mujeres a nivel mundial y en países en vía de desarrollo. En estos últimos los costos de los tratamientos son aún más preocupantes que en países de alto ingreso. La sobreexpresión de ErbB2 es marcador de pobre pronóstico y objetivo de terapias dirigidas. Se evaluó la costo-efectividad de los tratamientos de CSM ErbB2+ en progresión post-trastuzumab en Colombia. Métodos Se desarrolló un modelo analístico de decisiones para evaluar los tratamientos en una cohorte hipotética de CSM ErbB2+ que progresaron después de un primer esquema con trastuzumab. Las alternativas comparadas fueron: lapatinib+capecitabina (L+C), y trastuzumab más un agente quimioterápico (capecitabina, vinorelbinao un taxano). Se usaron modelos de Markov para calcular el tiempo libre de progresión y los costos asociados. Estimaciones de efectividad fueron identificadas de estudios primarios. Se incluyeron todos los costos médicos directos basados en los manuales tarifarios nacionales. Se realizaron análisis de sensibilidad y curvas de aceptabilidad. Se descontaron costos y resultados a una tasa anual de 3 %, la perspectiva de análisis fue del tercer pagador y el horizonte de 5 años. Resultados L+C domina a sus comparadores con un razón de costo-efectividad de COP $49 725 045 por año libre de progresión. Los factores que más influencian los resultados son los hazard ratios de las alternativas y el costo de trastuzumab. Conclusión Lapatinib es costo-efectivo comparado con sus alternativas para el tratamiento del CSM después de la progresión con trastuzumab en el escenario colombiano.

Náuseas, vômitos e qualidade de vida de mulheres com câncer de mama em tratamento quimioterápico / Náuseas, vómitos y calidad de vida en mujeres con cáncer de mama en la quimioterapia / Nausea, vomiting and quality of life in women with breast cancer receiving chemotherapy

Objetivou-se avaliar a qualidade de vida (QV) de mulheres com câncer de mama em tratamento quimioterápico e identificar a ocorrência de náuseas e vômitos durante o tratamento. Os dados foram coletados com a aplicação do instrumento da Organização Europeia de Pesquisa e Tratamento de Câncer, EORTC-QLQ-C30, na versão em português, bem como do módulo para câncer de mama BR-23, aplicados antes, no meio e ao final do tratamento. Das 79 mulheres incluídas, 93% apresentaram náuseas e 87% vômitos pelo menos uma vez durante o tratamento. A QV apresentou pequena diminuição durante o tratamento. O coeficiente alfa de Cronbach para cada aplicação dos questionários foi de 0,890492, 0,936392 e de 0,937639. A disponibilidade de informações sobre o tratamento e de orientações quanto ao manejo da náusea e do vômito é crucial para o gerenciamento adequado das toxicidades da quimioterapia.

Evaluar la calidad de vida (QOL) de las mujeres con cáncer de mama durante la quimioterapia e identificar el acontecimiento de náuseas y vómitos durante el tratamiento. Se recogieron datos con la aplicación del instrumento de la Organización Europea para la Investigación y Tratamiento del Cáncer, EORTC-QLQ-C30 versión en portugués y módulo para el cáncer de mama BR-23 aplicado antes, en la mitad y al final del tratamiento. Se incluyeron 79 mujeres, el 93% tuvo náuseas, el 87% vómitos al menos una vez durante el tratamiento. La QOL presentó una ligera disminución durante el tratamiento. El coeficiente alfa de Cronbach para cada aplicación de los cuestionarios fue 0.890492, 0.936392 y 0.937639. La disponibilidad de informaciones sobre el tratamiento y directrices sobre el manejo de la náusea y vómito es fundamental para la correcta gestión de las toxicidades de la quimioterapia.

The aim of this study was to assess the quality of life (QoL) of women with breast cancer during chemotherapy and to identify the incidence of nausea and vomiting during the treatment. Data were assessed with the application of the instrument of the European Organization for Research and Treatment of Cancer, EORTC-QLQ-C30 Portuguese version and breast cancer module BR-23, which was applied before, in the middle and in the end of the treatment. The participants were 79 women, of which 93% had nausea and 87% had vomited at least once during the treatment. QoL showed a slight decrease during treatment. Cronbach's alpha for each application of the questionnaires was 0.890492, 0.936392 and 0.937639. The availability of treatment information and guidelines on the management of nausea and vomiting is crucial for the proper management of the toxicities of chemotherapy.