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The evaluation and monitoring of sites contaminated with heavy metals are essential for pollution remediation and prevention. In this study, we conducted geophysical and geochemical investigations at a site exhibiting heavy metal contamination downstream from an abandoned mine, with the aim of analyzing the extent of contamination and its temporal variation. We employed geophysical survey methods including electrical resistivity and induced polarization surveys of areas contaminated with heavy metals. Repeated surveys were conducted over time using the electrical resistivity method. Numerical simulations were employed to mitigate and eliminate electrical noise stemming from topography on the site. Additionally, time-lapse inversion was conducted on the resistivity data sets to analyze the changes in resistivity caused by variations in heavy metal contaminants. In the geochemical survey, soil samples were collected from the same locations as the geophysical survey, and chemical properties including pH, water content, electrical conductivity, and cation exchange capacity were analyzed. Our results showed that with the reduction of major sources of As and Zn contamination by 50%, the time-lapse electrical resistivity inversion results indicated that the resistivity of the subsurface materials increased by a factor of two. This paper demonstrated the natural reduction of the heavy metal contaminants at the site due to rainfall, aiming to comprehensively analyze the resultant alteration of both geochemical and geophysical properties.
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Monitoramento Ambiental , Metais Pesados , Poluentes do Solo , Metais Pesados/análise , Poluentes do Solo/análise , República da Coreia , Solo/químicaRESUMO
BACKGROUND: To analyze the effects of socioeconomic status (type of insurance and income level) and cancer stage on the survival of patients with liver cancer in Korea. METHODS: A retrospective cohort study was constructed using data from the Healthcare Big Data Platform project in Korea between January 1, 2007, and December 31, 2017. A total of 143,511 patients in Korea diagnosed with liver cancer (International Classification of Diseases, 10th Revision [ICD-10] codes C22, C220, and C221) were followed for an average of 11 years. Of these, 110,443 died. The patient's insurance type and income level were used as indicators of socioeconomic status. Unadjusted and adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox proportional hazards regression model to analyze the relationship between the effects of sex, age, and cancer stage at first diagnosis (Surveillance, Epidemiology, and the End Results; SEER), type of insurance, and income level on the survival of patients with liver cancer. The interactive effects of the type of insurance, income level, and cancer stage on liver cancer death were also analyzed. RESULTS: The lowest income group (medical aid) showed a higher risk for mortality (HR (95% CI); 1.37 (1.27-1.47) for all patients, 1.44 (1.32-1.57) for men, and 1.16 (1.01-1.34) for women) compared to the highest income group (1-6) among liver cancer (ICD-10 code C22) patients. The risk of liver cancer death was also higher in the lowest income group with a distant cancer stage (SEER = 7) diagnosis than for any other group. CONCLUSION: Liver cancer patients with lower socioeconomic status and more severe cancer stages were at greater risk of death. Reducing social inequalities is needed to improve mortality rates among patients in lower social class groups who present with advanced cancer.
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Neoplasias Hepáticas , Classe Social , Masculino , Humanos , Feminino , Estudos de Coortes , Estudos Retrospectivos , Fatores Socioeconômicos , República da Coreia/epidemiologiaRESUMO
To effectively delineate the spatial distribution of oil contaminant plumes, geophysical methods indirectly measure the physical properties of the subsurface and can provide spatial information and images on a large scale, as opposed to traditional direct methods such as borehole drilling, sampling, and chemical analysis, which are time-consuming and costly. However, interpreting geophysical responses over non-aqueous phase liquid (NAPL)-contaminated sites is not straightforward due to inconsistent responses from biodegraded oil contaminants. In this study, we performed multi-geophysical surveys including seismic refraction, ground-penetrating radar, electrical resistivity tomography (ERT), and induced polarization (IP) surveys, to locate NAPL-contaminated zones in a clay-rich site. To reduce ambiguity in discriminating between oil contaminants and clay layers, we first figure out the geological structure of the site by interpreting geophysical data incorporating with borehole data. The ERT data highlighted the heavily contaminated regions in the unsaturated zone but were less distinctive below groundwater levels. Conversely, IP responses revealed potential hotspots within the clay layers, extending beneath the groundwater. Considering the 3D geological model, NAPL-contaminated zones are properly delineated through interpretation of ERT and IP data together with borehole data, and the contaminant source zone was properly estimated within the site.
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Monitoramento Ambiental , Água Subterrânea , Argila , Monitoramento Ambiental/métodos , Água Subterrânea/química , Eletricidade , Fenômenos FísicosRESUMO
Monitoring the leakage of leachate from a landfill is critical in preventing possible contamination in the surrounding area. Time-lapse (TL) electrical resistivity tomography (ERT) has been performed along eleven survey lines at four different time points in a landfill in Korea. The TL data sets were interpreted using an in-house 4D inversion algorithm. Changes in 4D inversion results were analyzed in order to interpret a leachate-contaminant region. Since the rainy season started during obtaining TL ERT data sets, the effects of precipitation on TL ERT data are also analyzed. Changes in electrical resistivity (ER) showed that precipitation increases ER of contaminant zones. As hydrogeochemical data offer contamination information in some areas where boreholes are located, these are helpful to interpret and compare with ERT inversion results to evaluate the extent of the contaminated plume. We also classified soil textures from particle size analysis on soil samples and analyzed electrical conductivity (EC) and dissolved oxygen (DO) using groundwater samples obtained from observation wells in the survey site. The information on soil structure as well as the results of 4D inversion provided insight into the location of a preferential flow path.
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Água Subterrânea , Poluentes Químicos da Água , Monitoramento Ambiental/métodos , Imagem com Lapso de Tempo , Poluentes Químicos da Água/análise , Instalações de Eliminação de Resíduos , Solo , Água Subterrânea/químicaRESUMO
BACKGROUND: The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established. AIM: To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC. METHODS: Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk. RESULTS: Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001). CONCLUSION: Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.
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BACKGROUND: We evaluated the accuracy of the prehospital Field Triage Decision Scheme, which has recently been applied in the Korean trauma system, and the factors associated with severe injury and prognosis at a regional trauma center in Korea. METHODS: From 2016 to 2018, prehospital data of injured patients were obtained from the emergency medical services of the national fire agency and matched with trauma outcomes at our institution. Severe injury (Injury Severity Score > 15), overtriage/undertriage rate, positive predictive value, negative predictive value, and accuracy were reviewed according to the triage protocol steps. A multivariate logistic regression analysis was performed to identify influencing factors in the field triage. RESULTS: Of the 2438 patients reviewed, 853 (35.0%) were severely injured. The protocol accuracy was as follows: step 1, 72.3%; step 2, 65.0%; step 3, 66.2%; step 1 or 2, 70.2%; and step 1, 2, or 3, 66.4%. Odds ratios (OR) (95% confidence interval [CIfor systolic blood pressure < 90 mmHg (3.535 [1.920-6.509]; p < 0.001), altered mental status (17.924 [8.980-35.777]; p < 0.001), and pedestrian injuries (2.473 [1.339-4.570], p = 0.04) were significantly associated with 24-h mortality. Penetrating torso injuries (7.108 [4.108-12.300]; p < 0.001); two or more proximal long bone fractures (4.134 [2.316-7.377]); p < 0.001); crushed, degloved, and mangled extremities (8.477 [4.068-17.663]; p < 0.001); amputation proximal to the wrist or ankle (42.964 [5.764-320.278]; p < 0.001); and fall from height (2.141 [1.497-3.062]; p < 0.001) were associated with 24-h surgical intervention. CONCLUSION: The Korean field triage protocol is not yet accurate, with only some factors reflecting injury severity, making reevaluation necessary.
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Serviços Médicos de Emergência , Ferimentos e Lesões , Ferimentos Penetrantes , Adulto , Humanos , Escala de Gravidade do Ferimento , Valor Preditivo dos Testes , Estudos Retrospectivos , Centros de Traumatologia , Triagem/métodos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/terapiaRESUMO
BACKGROUND: To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. METHODS: Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. RESULTS: A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). CONCLUSION: Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.
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BACKGROUND: Combination therapy with oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) chemotherapy drastically improves survival of advanced pancreatic cancer patients. However, the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively. We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer. METHODS: A multicenter phase II prospective open-label, single-arm study was conducted at 14 hospitals. Patients with histologically proven invasive ductal pancreatic adenocarcinoma, a measurable or evaluable lesion, Eastern Cooperative Oncology Group performance status 0 or 1, adequate organ function, and aged 19 years or older were eligible. Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2, irinotecan 135 mg/m2, and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2, repeated every 2 weeks. The primary endpoint was progression-free survival from the initiation of FOLFIRINOX. Secondary endpoints were the objective response rate, disease control rate, overall survival, safety, and tolerability. We estimated overall survival and progression-free survival using the Kaplan-Meier methods. RESULTS: We enrolled 39 patients from 14 institutions. The objective response rate was 10.3%, while the disease control rate was 64.1%. The 6-month and 1-year overall survival rates were 59.0% and 15.4%, respectively. Median progression-free survival and overall survival were 3.8 months (95% confidence interval [CI] 1.5-6.0 months) and 8.5 months (95% CI 5.6-11.4 months), respectively. Grade 3 or 4 adverse events were neutropenia (41.0%), nausea (10.3%), anorexia (10.3%), anemia (7.7%), mucositis (7.7%), pneumonia/pleural effusion (5.1%), and fatigue (5.1%). One treatment-related death attributable to septic shock occurred. CONCLUSION: Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancreatic cancer.
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Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Terapia de Salvação/métodos , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Irinotecano/administração & dosagem , Irinotecano/efeitos adversos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Neutropenia/induzido quimicamente , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Estudos Prospectivos , Terapia de Salvação/efeitos adversos , GencitabinaRESUMO
OBJECTIVE: The aim of this study was to assess the feasibility of a modified FOLFOX regimen as first-line treatment in elderly patients with metastatic gastric cancer (GC) or colorectal cancer (CRC). METHODS: We included chemotherapy-naïve patients over 80 years old with metastatic GC or CRC in our study. From September 2008 to November 2014, 28 consecutive patients were enrolled and treated with modified FOLFOX. RESULTS: The study population consisted of an equal number of GC and CRC patients. The median age was 82.2 years in the GC group and 81.1 years in the CRC group. The total number of administered cycles was 89 (with a median of 6 per patient) in the GC group and 112 (with a median of 8 per patient) in the CRC group. Median progression-free survival (PFS) and overall survival (OS) were 5.4 and 6.6 months in the GC group and 7.3 and 8.1 months in the CRC group, respectively. There was no significant difference in PFS (p = 0.941) and OS (p = 0.238) between the GC and the CRC group. The 1-year survival rates were 35.7% with GC and 42.9% with CRC. Common grade 3/4 hematology toxicities were neutropenia (10.7%) and anemia (14.3%). Salvage chemotherapy was administered to 1 patient with GC and 7 patients with CRC. CONCLUSIONS: The modified FOLFOX regimen can be cautiously considered as a first-line treatment option in extremely elderly patients with metastatic GC or CRC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Estudos de Viabilidade , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Metástase Neoplásica/terapia , Compostos Organoplatínicos/uso terapêutico , República da Coreia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Renal cell carcinomas (RCCs) have a strong tendency to metastasize, and the most common sites are the lungs, bones and liver. Late recurrence is another feature of the RCC, with lesions appearing ≥10 years after surgical treatment. However, fibrosis has rarely been associated with the disease. The present study reports a case of recurrent RCC that manifested as a fibrotic mass within the thorax. A 48-year-old man presented with dyspnea that had persisted for 3 days. The patient had undergone a right radical nephrectomy for stage II clear cell carcinoma of the kidney 6 years previously. The patient was a current smoker, with a smoking history of 20 pack-years. Chest radiography showed pleural effusion in the right thorax with an egg-sized mass shadow within the right upper lung (RUL) field. Computed tomography (CT) showed a main mass, 7 cm in diameter, within the RUL, with heterogeneous enhancement and multiple nodules of various sizes in the lungs, suggestive of primary lung cancer or metastatic RCC. A CT-guided percutaneous needle aspiration biopsy was obtained from the main mass, but histology revealed dense fibrous tissue without any malignant cells. Positron emission tomography-CT demonstrated an irregular hypermetabolic RUL mass, with a standardized uptake value (SUV) of 5.0, along the right pleura, and small pulmonary nodules (SUV, 2.0). Ultrasound-guided biopsy was attempted for a smaller hypermetabolic pleural nodule and the result was clear cell adenocarcinoma, consistent with the previous renal histology. The present study describes the case, along with a review of the relevant literature.
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Krukenberg tumor, a rare metastatic ovarian tumor arising from gastrointestinal adenocarcinoma mainly, tends to occur in premenopausal females. Finding the origin of a Krukenberg tumor is crucial for determining prognosis. In Eastern countries, the most common origin of Krukenberg tumor is stomach cancer, which is generally diagnosed via endoscopic biopsy to investigate an abnormal mucosal lesion. Here, we describe a case of huge adnexal mass in a 33-year-old woman who presented with abdominal distension. Two independent endoscopic examinations performed by experts in two tertiary university hospitals revealed no abnormal mucosal lesion. The patient was diagnosed with a Krukenberg tumor according to findings from random endoscopic biopsies taken from normal-looking gastric mucosa in our hospital. It is very rare to be diagnosed via a random biopsy in cases where three well-trained endoscopists had not found any mucosal lesion previously. Thus, in this case, random biopsy was helpful in finding the origin of a Krukenberg tumor.
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Mucosa Gástrica/patologia , Tumor de Krukenberg/secundário , Neoplasias Ovarianas/secundário , Neoplasias Gástricas/patologia , Adulto , Biópsia , Colonoscopia , Progressão da Doença , Evolução Fatal , Feminino , Gastroscopia , Humanos , Tumor de Krukenberg/diagnóstico por imagem , Tumor de Krukenberg/tratamento farmacológico , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento , Imagem Corporal Total/métodosRESUMO
The use of renal replacement therapy (RRT) in patients receiving extracorporeal membrane oxygenation (ECMO) is increasing, but the effect of RRT on ECMO is controversial. We performed a meta-analysis to determine whether RRT is related to higher mortality in patients receiving ECMO. We searched MEDLINE, EMBASE, the Cochrane Library, and KoreaMed and found 43 observational studies with 21,624 patients receiving ECMO and then compared inpatient mortality rates of patients receiving ECMO both with and without RRT. The risk ratio (RR) of mortality between patients receiving RRT and those not receiving RRT tended to decrease as the mortality of the group not receiving RRT increased. Among patients with RRT use rates of 30% and higher, the overall mortality rates for all patients receiving ECMO tended to decrease. We found that the increase in the RR for RRT tended to be greater the longer the initiation of RRT was delayed. We suggest that in patients receiving ECMO who have high RRT use rates, RRT may decrease mortality rates.
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Oxigenação por Membrana Extracorpórea , Terapia de Substituição Renal , HumanosRESUMO
BACKGROUND/AIMS: Little is known about the efficacy of low-dose transdermal fentanyl (TDF) patches in opioid-naïve patients with moderate-to-severe cancer pain. METHODS: This study had an open-label, prospective design, and was conducted between April 2007 and February 2009 in seven tertiary cancer hospitals; 98 patients were enrolled. TDF was started using a low-dose formulation (12.5 µg/hr), and the dose was adjusted according to the clinical situation of individual patients. Pain intensity, the TDF doses used, and adverse events (AEs) were monitored over 4 weeks. Data were analyzed using the intent-to-treat and per-protocol principles. RESULTS: Of the 98 patients enrolled, 64 (65%) completed the study. The median pain intensity decreased from 6.0 to 3.0 (p < 0.001) at the follow-up visit. The efficacy of low-dose TDF on pain relief was consistent across groups separated according to gender (p < 0.001), age (p < 0.001), metastasis (p < 0.001), previous treatment (p < 0.001), and baseline pain intensity (p < 0.001). The decrease in pain intensity was significantly greater in the severe group compared with the moderate group (mean ± SD, 5.10 ± 2.48 vs. 2.48 ± 1.56; p < 0.001). TDF dose (27.8 µg/hr vs. 24.8 µg/hr, p = 0.423) and the mean treatment time (7.5 days vs. 7.9 days, p = 0.740) required for pain control were not different between the two pain-intensity groups. Patients had AEs of only mild or moderate intensity; among these, nausea (38%) was the most common, followed by vomiting (22%) and somnolence (22%). CONCLUSIONS: Low-dose TDF was an effective treatment for patients with cancer pain of moderate-to-severe intensity. Further randomized trials assessing the efficacy of TDF for severe pain and/or optimal starting doses are warranted.
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Analgésicos Opioides/administração & dosagem , Fentanila/administração & dosagem , Neoplasias/complicações , Dor/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/efeitos adversos , Feminino , Fentanila/efeitos adversos , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , Dor/etiologia , Medição da Dor , Estudos Prospectivos , República da Coreia , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fatores de Tempo , Adesivo Transdérmico , Resultado do TratamentoRESUMO
Bleomycin has been used most commonly in the treatment of Hodgkin's lymphoma, certain germ cell tumors (GCT) and for the sclerosis of recurrent pleural effusions. Bleomycin toxicity predominantly affects the skin and lungs. Skin toxicity includes Raynaud's phenomenon, hyperkeratosis, nail-bed changes and palmoplantar desquamation. Flagellate erythema is an unusual rash occurring specifically during bleomycin use. In the present study, we report a case of bleomycin-induced flagellate erythema in a patient with GCT. A 42-year-old male was diagnosed with stage IIIB testicular cancer and treated with bleomycin, etoposide and cisplatin chemotherapy. After 10 days from the initiation of treatment, the patient subsequently developed a generalized pruritus and erythematous linear rash that was most prominent on the trunk, and upper and lower extremities. The patient was commenced on a short course of low-dose oral prednisolone, 20 mg daily, and antihistamine. Consequently, bleomycin was withheld from the patient's treatment regimen. The present study describes the case, along with a review of the associated literature.
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Current practice guidelines recommend the combination of chemotherapy and thoracic radiation for locally advanced non-small cell lung cancer (NSCLC). Previous meta-analyses have shown that concurrent chemoradiation (CCRT) may be superior to sequential chemoradiation (SCRT). However, few previous in vitro studies have analyzed these two treatment schedules. In the current study, four lung cancer cell lines harboring wild-type epidermal growth factor receptor, comprising two squamous and two non-squamous cell lines, were used. The IC10 concentrations of three platinum-based regimens were combined with radiation treatment. Cells were irradiated at 0, 2, 4, 6 and 8 Gy using a 137Cs irradiator concurrently or sequentially. Surviving fractions (SFs) were plotted as a function of the radiation dose. In A549 cells, only the docetaxel (Doc) and carboplatin (Carbo) combination showed a significant radiosensitizing effect with CCRT treatment. For the other three cell lines, no difference was identified in the SFs between CCRT and SCRT. An in vitro method of comparing CCRT with SCRT was established using lung cancer cell lines. Overall, no significant difference was detected in the radiosensitizing effect of the two treatment schedules, with the exception of the A549 cell lines treated with Doc/Carbo.
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BACKGROUND: Statins have potential antineoplastic properties via arrest of cell-cycle progression and induction of apoptosis. A previous study demonstrated in vitro and in vivo antineoplastic synergism between statins and gemcitabine. The present randomized, double-blinded, phase II trial compared the efficacy and safety of gemcitabine plus simvastatin (GS) with those of gemcitabine plus placebo (GP) in patients with locally advanced and metastatic pancreatic cancer. METHODS: Patients were randomly assigned to receive a 3-week regimen with GS (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus simvastatin 40 mg once daily) or GP (gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 plus placebo). The primary end point was time to progression (TTP). RESULTS: Between December 2008 and April 2012, 114 patients were enrolled. The median TTP was not significantly different between the two arms, being 2.4 months (95 % CI 0.7-4.1 months) and 3.6 months (95 % CI 3.1-4.1 months) in the GS and GP arms, respectively (P = 0.903). The overall disease control rate was 39.7 % (95 % CI 12.2-33.8 %) and 57.1 % (95 % CI 19.8-44.2 %) in the GS and GP arms, respectively (P = 0.09). The 1-year expected survival rates were similar (27.7 and 31.7 % in the GS and GP arms, respectively; P = 0.654). Occurrence of grade 3 or 4 adverse events was similar in both arms, and no patients had rhabdomyolysis. CONCLUSIONS: Adding low-dose simvastatin to gemcitabine in advanced pancreatic cancer does not provide clinical benefit, although it also does not result in increased toxicity. Given the emerging role of statins in overcoming resistance to anti-EGFR treatment, further studies are justified to evaluate the efficacy and safety of combined simvastatin and anti-EGFR agents, such as erlotinib or cetuximab, plus gemcitabine for treating advanced pancreatic cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Sinvastatina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Método Duplo-Cego , Receptores ErbB/antagonistas & inibidores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias Pancreáticas/mortalidade , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/genética , GencitabinaRESUMO
BACKGROUND: Although platinum-based chemotherapy is a standard first-line treatment in advanced non-small cell lung cancer (NSCLC), further research for the safety and efficacy of combination chemotherapy in elderly patients has been required. The purpose of this study was to evaluate the efficacy and safety of gemcitabine and carboplatin as first-line treatment in elderly patients with advanced NSCLC and to evaluate the prognostic factors. METHODS: Eligibility included: (1) age of 70 years or more, (2) histologically confirmed NSCLC, (3) chemotherapy-naïve, (4) advanced disease with stage IIIB or IV, (5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, (6) adequate organ function. Patients received intravenous carboplatin (area under curve (AUC) = 5) on day 1 and gemcitabine (1000 mg/m2) on days 1 and 8, every 3 weeks. RESULTS: The medical records of forty patients were reviewed retrospectively. Median age was 73.9 years (range, 70-84.6), and there were 27 men (67.5%). Thirty-seven patients (92.5%) had ECOG PS 0-1. Adenocarcinoma was found in 57.5%. Median cycles were administrated with 4.5 per person (range: 1-6). Best responses were partial response in 22 (55.0%) patients and stable disease (SD) in 13 (32.5%). The median progression free survival (PFS) and overall survival (OS) were 5.9 months (95% CI: 4.5-7.3 months) and 9.6 months (95% CI: 8.2-11.0 months), respectively. Grade 4 hematologic toxicities for neutropenia (7.5%), thrombocytopenia (7.5%) and anemia (5.0%) were observed. Histology was significant prognostic factor for PFS (P = 0.024). CONCLUSION: Gemcitabine and carboplatin combination chemotherapy is an effective and manageable treatment option in elderly advanced NSCLC patients with good performance status.
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Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , GencitabinaRESUMO
Pemetrexed is approved as a first-line treatment for advanced non-squamous non-small cell lung cancer (NSCLC) with cisplatin and as a single agent for second-line treatment or for patients who show no disease progression after four cycles of platinum-based doublet induction chemotherapy as maintenance therapy. Pemetrexed has a modest toxicity profile and has not traditionally been regarded as a cause of interstitial pneumonitis. Here, we report on a rare case of pemetrexed-induced pneumonitis in a patient with NSCLC.
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Smad7, an inhibitory Smad, acts as a key regulator forming autoinhibitory feedback loop in transforming growth factor-beta (TGF-ß) signaling. However, a growing body of evidences suggests that Smad7 is capable of apoptotic function. In the present study, we have demonstrated a proapoptotic function of Smad7 as a negative regulator of survival protein heme oxygenase-1 (HO-1). The HO-1 protein level was elevated in cisplatin-resistant A549 human lung cancer cells and blockade of HO-1 activation sensitized the cells to apoptosis. Interestingly, overexpression of Smad7 decreased HO-1 gene expression and its enzymatic activity. Notably, Smad7 reduced Akt activity and infection with adenovirus expressing a constitutively active form of the Akt reversed the inhibitory effects of Smad7 to HO-1, indicating a negative action mechanism of Smad7 to Akt-HO-1-linked survival pathway. Consistently, Smad7 sensitized A549 cells to cisplatin-induced apoptosis and these effects were dependent on HO-1 and Akt inhibition. Based on these findings, we suggest that targeting Smad7 may be an efficient strategy for overcoming drug-resistance in cancer therapy.
Assuntos
Apoptose/genética , Resistencia a Medicamentos Antineoplásicos/genética , Heme Oxigenase-1/antagonistas & inibidores , Neoplasias Pulmonares/metabolismo , Proteína Smad7/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Heme Oxigenase-1/genética , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Smad7/genéticaRESUMO
Most of the malignant neoplasms of the pancreas demonstrate features that are consistent with adenocarcinoma. According to the WHO classification, primary clear cell carcinoma of the pancreas is rare and it is classified as a "miscellaneous" carcinoma. In addition, there is not an adequate systematic overview that can demonstrate its true existence as a definable entity. We report here on an unusual case of primary pancreatic clear cell carcinoma, which is the first such reported case in Korea. A 66 year old woman presented with abdominal pain and significant weight loss over the previous three weeks. On the abdominal computed tomography (CT), we detected an abdominal mass involving the pancreas tail and liver, and clear cell carcinoma with rhabdoid feature was seen on the histologic evaluation. The tumor cells showed well defined cell membranes, clear cytoplasm and prominent cell boundaries. The immunohistochemical stains showed positive reactions to antibodies against pan-cytokeratin, cytokeratin 7, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). On the other hand, there was a negative reaction for cytokeratin 20, chromogranin, synaptophysin, smooth muscle actin and HMB-45. She was diagnosed with a primary pancreatic clear cell carcinoma with hepatic metastasis and she received palliative gemcitabine chemotherapy. The patient died one month later of pancreatic cancer progression.