Osimertinibe comparado a Erlotinibe Gefitinibe ou quimioterapia para tratamento de carcinoma pulmonar de células não pequenas com mutação do gene do receptor do fator de crescimento epidérmico (EFGR): revisão rápida / Osimertinib compared to erlotinib, gefitinib or chemotherapy for the treatment of non-small cell pumonary carcinoma with epidermal growth factor receptor (EFGR) gene mutation: rapid review

Mesilato de osimertinibe, gefitinibe, erlotinibe, quimioterapia padrão. Indicação: Câncer de pulmão de células não pequenas com mutação do receptor do fator de crescimento epidérmico (EGFR). Pergunta: Mesilato de osimertinibe é mais eficaz e seguro que gefitinibe, erlotinibe ou quimioterapia para os desfechos de sobrevida global, sobrevida livre de progressão e de segurança no tratamento de carcinoma pulmonar de células não pequenas com mutação do EGFR? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e EPISTEMONIKOS, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionadas duas revisões sistemáticas que atenderam aos critérios de elegibilidade. Conclusão: Mesilato de osimertinibe é mais eficaz do que gefitinibe ou erlotinibe na melhora da sobrevida global e da sobrevida livre de progressão em pacientes virgens de tratamento. Em pacientes previamente tratados, o mesilato de osimertinibe não é superior à quimioterapia padrão à base de platina no prolongamento da sobrevida global, mas é mais eficaz no aumento da sobrevida livre de progressão. Para câncer avançado, mesilato de osimertinibe não é mais eficaz do que a quimioterapia com ou sem pemetrexede para prolongar a sobrevida global, mas é mais eficaz em melhorar a sobrevida livre de progressão. Gefitinibe combinado com quimioterapia à base de pemetrexede foi superior à quimioterapia com ou sem pemetrexede na melhora da sobrevida global e da sobrevida livre de progressão

Osimertinib mesylate, gefitinib, erlotinib, standard chemotherapy. Indication: Non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutation. Question: Is osimertinib mesylate more effective and safer than gefitinib, erlotinib or chemotherapy for overall survival, progression-free survival and safety outcomes in the treatment of non-small cell lung cancer with EGFR mutation? Methods: A bibliographic search was done in the PUBMED and EPISTEMONIKOS database, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the Assessing the Methodological Quality of Systematic Reviews Version 2 tool. Results: Two systematic reviews were selected because they met the eligibility criteria. Conclusion: Osimertinib mesylate is more effective than gefitinib or erlotinib in improving overall survival and progression-free survival in treatment-naive patients. In previously treated patients, osimertinib mesylate is not superior to standard platinum-based chemotherapy in prolonging overall survival, but it is more effective in increasing progression-free survival. For advanced cancer, osimertinib mesylate is not more effective than chemotherapy with or without pemetrexed in prolonging overall survival, but it is more effective in improving progression-free survival. Gefitinib combined with pemetrexed-based chemotherapy was superior to chemotherapy with or without pemetrexed in improving overall survival and progression-free survival

A case of malignant peritoneal mesothelioma / 中华劳动卫生职业病杂志

Malignant mesothelioma is a highly malignant disease that most often occurs in the pleural cavity, followed by the peritoneum and pericardium. Malignant peritoneal mesothelioma (MPM) accounts for 10%-15% of all mesothelioma. The most important risk factor for MPM is exposure to asbestos. MPM has no specific clinical symptoms, imaging and histopathology are critical for the diagnosis. There are currently no generally accepted guidelines for curative treatment of MPM. The patient mainly presented with abdominal pain, abdominal distension and discomfort. Due to extensive omentum metastasis, no further surgical treatment was performed. Pemetrexed combined with cisplatin chemotherapy was given for 2 cycles, and the patient is still alive.

Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors / 中华肿瘤杂志

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

Analysis of the Efficacy of Pemetrexed Maintenance Therapy in Patients with Malignant Pleural Mesothelioma / 中国肺癌杂志

BACKGROUND@#Malignant pleural mesothelioma (MPM) is a highly aggressive disease arising from pleural mesothelial cells. Advanced pleural mesothelioma has a poor prognosis, with a median survival of no more than 15 months. First line standard chemotherapy regimen recommended is Pemetrexed based chemotherapy regimen, with or without bevacizumab. There is no consensus on whether patients who have received first-line standard chemotherapy can benefit from pemetrexed maintenance chemotherapy. The study aimed to investigate the efficacy and safety of pemetrexed maintenance therapy (PMT) after treatment with a pemetrexed and platinum regimen for patients with MPM.@*METHODS@#A total of 40 MPM patients were collected from Cancer Hospital Chinese Academy of Medical Sciences from January 2013 to January 2018, eligible patients were unresectable MPM, without disease progression following 4 to 6 cycles of pemetrexed and platinum, including pemetrexed maintenance therapy group (22 cases) and observation group (18 cases). The last follow-up was conducted in January 2020. The primary endpoint were progression free survival (PFS), and the secondary end points were overall survival (OS), the efficacy, adverse reactions of PMT.@*RESULTS@#The median PFS in the PMT arm was longer than that in the observation arm (8.5 mon vs 3 mon, P=0.008), but there was no significant difference in median OS (26.4 mon vs 15.7 mon, P=0.177). Objective response rate (ORR) of two group were 22.7% and 0%, respectively. The grade 3-4 toxicity in PMT group included grade 4 neutropenia in 1 patient (4.5%), grade 3 neutropenia in 1 patient (4.5%), grade 4 anemia in 1 patient (4.5%) and grade 3 nausea and anorexia in 1 patient (4.5%).@*CONCLUSIONS@#Pemetrexed maintenance therapy following initial pemetrexed and platinum chemotherapy improve PFS in patients with MPM, and is well tolerated.

Efeito do momento de imersão na alteração volumétrica do agregado trióxido mineral HP / Effect of the immersion moment at the volumetric alteration of the mineral trioxide aggregate HP

Introdução: A solubilidade é uma propriedade relaciona- da à dissociação dos constituintes do material, pela ação do contato com o líquido circundante. Introdução: O objetivo do presente estudo foi avaliar o efeito da hidratação durante a varredura com microtomografia (micro-TC) sobre a alteração volumétrica do MTA HP. Métodos: foram utilizados 20 dentes incisivos superiores de acrílico com cavidade retrógrada. O cimento MTA HP foi inserido na cavidade com um condensador Paiva. As amostras foram inspecionadas visualmente com uma lupa de 5x, para garantir que não permanecessem espaços vazios ou lacunas. Os espécimes foram divididos em dois grupos (n=10). Os dentes foram escaneados logo após o manuseio do MTA. Para o grupo com imersão em água, Eppendorf hidratado foi mantido com 1mL de água durante a varredura; no outro grupo, os dentes foram escaneados sem água. Nos dois grupos, os dentes foram imersos em água durante sete dias. Em seguida, os dentes foram escaneados novamente em micro-TC usando os mesmos parâmetros e condições de cada grupo. Foi realizada a reconstrução das imagens pelo software Nrecon e o volume de solubilidade, determinado pelo software CTan, analisando-se a variação volumétrica. Resultados: O grupo de corpos de prova escaneados imersos na água apresentou maior variação volumétrica, com diferenças estatisticamente significativas em relação ao grupo escaneado sem imersão. O escaneamento do corpo de prova imerso em água favorece uma maior perda volumétrica do material. Conclusão: Os estudos para avaliar a variação volumétrica de cimentos de silicato de cálcio devem ser feitos com imersão em água.

Introduction: Solubility is a property related to the dissocia- tion of the constituents of the material by the action of contact with the surrounding liquid, for this reason, the aim of this study was to evaluate the effect of the hydration during the scanning in the microtomography on the volumetric alteration of the MTA HP. Methods: Twenty acrylic teeth upper incisor with retrograde cavity were utilized. The MTA HP cement was inserted into the cavity using a Paiva condensor. The specimens were visually inspected with a 5x magnifying glass to ensure they did not remain void or gaps. The specimens were divided into 2 groups (n=10). The teeth were scanned shortly after handling the MTA. For the group with water immersion, hydrated Eppendorf was kept with 1mL the water during the scanning and the other group, the teeth were scanning without water. In the two groups the teeth were immersed into water during 7 days. Next the teeth were newly scanned in the Micro-CT using the same parameters and conditions of each group. Reconstruction of images by the Nrecon software and the solubility volume determined by the CTan, analyzing the volumetric change. Results: The group of specimens scanned immersed into the water presented higher volumetric change with statistically significant differences in relation the group scanned without immersion. The scanning of the specimen immersed in water favors the greater volumetric loss of the material. Conclusion: Studies to evaluate volumetric change of calcium silicate cements should be made immersed in wate

Different techniques for the treatment of teeth with an incomplete root development and pulp necrosis: a systematic review / Diferentes técnicas para o tratamento de dentes com rizogênese incompleta e necrose pulpar: uma revisão sistemática

Introduction: The objective of this systematic review was to compare the apexification techniques of calcium hydroxide (Ca(OH)2), or mineral trioxide aggregate (MTA), with the pulp regeneration technique, using cohort studies, and non-randomized and randomized clinical trials. Methods: The methodology was based on electronic research in the following databases: PubMed, MEDLINE, Google Scholar, SciELO, and LILACS. In addition, a manual search was carried out using the references that were listed in the articles found. Results: A total of 403 potentially eligible studies were found, with seven being included in the inclusion criteria of this systematic review. The seven studies involved a total of 312 teeth. The minimum time of a follow-up period was 12 months. The irrigation solution most used was sodium hypochlorite, for both of the apexification and revascularization techniques. The medication commonly chosen in the apexification groups was Ca(OH)2, with antibiotic triple paste in the revascularization groups. The clinical rate of success in the groups treated with revascularization varied from 76% to 100%, while in the groups treated with apexification, it ranged from 68% to 100%. Only two studies reached a success rate equal to 100%. Conclusions: Variable levels of evidence were observed in relation to the treatments. However, it was confirmed that revascularization is an excellent option since its outcomes produced a greater gain of thickness and root length, besides developing a decrease in the apical foramen.

Introdução: O objetivo desta revisão sistemática foi comparar as técnicas de apexificação, com hidróxido de cálcio (Ca(OH)2) ou agregado trióxido mineral (MTA), com a técnica de regeneração pulpar, utilizando estudos coorte, ensaio clínico não randomizado e randomizado. Métodos: A metodologia foi baseada em pesquisa eletrônica nas seguintes bases de dados: PubMed, MEDLINE, Google Acadêmico, SciELO e LILACS. Além disso, foi realizada uma pesquisa manual utilizando as referências listadas nos artigos encontrados. Resultados: Foram encontrados 403 estudos potencialmente elegíveis, sendo sete incluídos nos critérios de inclusão desta revisão sistemática. Os sete estudos envolveram um total de 312 dentes. O tempo mínimo de um período de acompanhamento foi de 12 meses. A solução de irrigação mais utilizada foi o hipoclorito de sódio, para as técnicas de apexificação e revascularização. O medicamento comumente escolhido nos grupos de apexificação foi o Ca(OH)2, com pasta tripla antibiótica nos grupos de revascularização. A taxa clínica de sucesso nos grupos tratados com revascularização variou de 76% a 100%, enquanto nos grupos tratados com apexificação variou de 68% a 100%. Apenas dois estudos atingiram uma taxa de sucesso igual a 100%. Conclusões: Níveis variáveis de evidência foram observados em relação aos tratamentos. No entanto, confirmou-se que a revascularização é uma excelente opção, pois seus desfechos produzem maior ganho de espessura e comprimento radicular, além de diminuir o forame apical.

Mesotelioma en paciente colombiano con sobrevida mayor a tres años: presentación de caso / Mesothelioma in a Colombian Patient over three years: Case Presentation / Mesotelioma em paciente colombiano com sobrevivência superior a três anos: apresentação de caso

Resumen Introducción: el mesotelioma epitelioide es un tumor que se desarrolla en las capas embrionarias mesoteliales; es de etiología desconocida, pero se relaciona con la exposición al asbesto, con una presentación clínica inespecífica y con un pronóstico de sobrevida corto después del diagnóstico. Presentación del caso: hombre de profesión mecánico automotor, con tos sin expectoración, disnea, hipertermia y emaciación posterior a la extracción quirúrgica de lipomas que afectaban el tórax, quien posteriormente fue diagnosticado con mesotelioma epitelioide maligno con ubicación en la pleura del hemitórax derecho y fue tratado con toracotomía, quimioterapia con los medicamentos pemetrexed y cisplatino y sesiones de radioterapia, que mostraron un aumento en la sobrevida 3 tres años. Conclusión: este caso permitió identificar que el uso de la pleurodesis química con quimioterapia como tratamiento podría ser responsable del aumento de la esperanza de vida y la calidad de esta en los pacientes que padecen este tipo de tumor.

Abstract Introduction: Epithelioid mesothelioma is a tumor that develops in the mesothelial embryonic layers; it is of an unknown etiology, but it is related to asbestos exposure with a nonspecific clinical presentation and a short survival prognosis after diagnosis. Case presentation: An automotive mechanic patient presents with cough without expectoration, dyspnea, hyperthermia, and emaciation following surgical removal of lipomas. This affected the chest and the patient was subsequently diagnosed with malignant epithelioid mesothelioma located in the pleura of the right hemithorax. The patient was treated with thoracotomy, chemotherapy with the drugs pemetrexed and cisplatin, and radiation therapy sessions which resulted in an increased survival rate at 4 years. Conclusion: This case report identifies the use of chemical pleurodesis in combination with chemotherapy as an effective treatment for increasing the life expectancy and quality of life in patients suffering from this type of tumor.

Resumo Introdução: o mesotelioma epitelióide é um tumor que se desenvolve nas camadas embrionárias mesote-liais; é de causa desconhecida, mas está relacionado com a exposição ao amianto e possui uma manifestação clínica inespecífica e com prognóstico de sobrevivência curto após o diagnóstico. Apresentação do caso: o paciente é um mecânico automotivo, que apresentou tosse seca, dispneia, hipertermia e emagrecimento posterior a extração cirúrgica de lipomas que afetavam o tórax sendo posteriormente diagnosticado com mesotelioma epitelióide maligno localizado na pleura do hemitórax direito e foi tratado com toracotomia, quimioterapia com os medicamentos pemetrexed e cisplatino além de sessões de radioterapia, mostrando um aumento de expectativa de vida para 4 anos. Conclusão: este estudo de caso permite identificar que o uso da pleurodese química com quimioterapia como tratamento poderia ser a responsável pelo aumento da expectativa e qualidade de vida em pacientes acometidos por este tipo de tumor.

Cytocompatibility and cell proliferation evaluation of calcium phosphate-based root canal sealers

OBJECTIVES: This study aimed to evaluate the cell viability and migration of Endosequence Bioceramic Root Canal Sealer (BC Sealer) compared to MTA Fillapex and AH Plus.MATERIALS AND METHODS: BC Sealer, MTA Fillapex, and AH Plus were placed in contact with culture medium to obtain sealers extracts in dilution 1:1, 1:2 and 1:4. 3T3 cells were plated and exposed to the extracts. Cell viability and migration were assessed by 3-(4,5-dimethyl-thiazoyl)-2,5-diphenyl-tetrazolium bromide (MTT) and Scratch assay, respectively. Data were analyzed by Kruskal-Wallis and Dunn's test (p < 0.05).RESULTS: The MTT assay revealed greater cytotoxicity for AH Plus and MTA Fillapex at 1:1 dilution when compared to control (p < 0.05). At 1:2 and 1:4 dilutions, all sealers were similar to control (p > 0.05) and MTA Fillapex was more cytotoxic than BC Sealer (p < 0.05). Scratch assay demonstrated the continuous closure of the wound according to time. At 30 hours, the control group presented closure of the wound (p < 0.05). At 36 hours, only BC Sealer presented the closure when compared to AH Plus and MTA Fillapex (p < 0.05). At 42 hours, AH Plus and MTA Fillapex showed a wound healing (p > 0.05).CONCLUSIONS: All tested sealers demonstrated cell viability highlighting BC Sealer, which showed increased cell migration capacity suggesting that this sealer may achieve better tissue repair when compared to other tested sealers.

Bioactivity of endodontic biomaterials on dental pulp stem cells through dentin

OBJECTIVES: This study investigated the indirect effect of calcium-enriched mixture (CEM) cement and mineral trioxide aggregate (MTA), as 2 calcium silicate-based hydraulic cements, on human dental pulp stem cells (hDPSCs) through different dentin thicknesses.MATERIALS AND METHODS: Two-chamber setups were designed to simulate indirect pulp capping (IPC). Human molars were sectioned to obtain 0.1-, 0.3-, and 0.5-mm-thick dentin discs, which were placed between the 2 chambers to simulate an IPC procedure. Then, MTA and CEM were applied on one side of the discs, while hDPSCs were cultured on the other side. After 2 weeks of incubation, the cells were removed, and cell proliferation, morphology, and attachment to the discs were evaluated under scanning electron microscopy (SEM). Energy-dispersive X-ray (EDXA) spectroscopy was performed for elemental analysis. Alkaline phosphatase (ALP) activity was assessed quantitatively. The data were analyzed using the Kruskal-Wallis and Mann-Whitney tests.RESULTS: SEM micrographs revealed elongated cells, collagen fibers, and calcified nucleations in all samples. EDXA verified that the calcified nucleations consisted of calcium phosphate. The largest calcifications were seen in the 0.1-mm-thick dentin subgroups. There was no significant difference in ALP activity across the CEM subgroups; however, ALP activity was significantly lower in the 0.1-mm-thick dentin subgroup than in the other MTA subgroups (p < 0.05).CONCLUSIONS: The employed capping biomaterials exerted biological activity on hDPSCs, as shown by cell proliferation, morphology, and attachment and calcific precipitations, through 0.1- to 0.5-mm-thick layers of dentin. In IPC, the bioactivity of these endodontic biomaterials is probably beneficial.

A micro-computed tomography evaluation of voids using calcium silicate-based materials in teeth with simulated internal root resorption

OBJECTIVES: The obturation quality of MTA, Biodentine, Total Fill BC root canal sealer (RCS), and warm gutta-percha (WGP) in teeth with simulated internal root resorption (IRR) was evaluated by using micro-computed tomography.MATERIALS AND METHODS: Standardized IRR cavities were created using 40 extracted maxillary central incisor teeth and randomly assigned into 4 groups (n = 10). IRR cavities were filled with MTA, Biodentine, Total Fill BC RCS (bulk-fill form) and WGP + Total Fill BC RCS. Percentage of voids between resorptive cavity walls and obturation material (external void), and inside the filling materials (internal voids) were measured.RESULTS: Total Fill BC sealer in the bulk-fill form presented significantly highest values of external and internal void percentages (p < 0.05). Biodentine showed a significantly lowest external void percentage (p < 0.05). WGP + Total Fill BC RCS presented significantly lower values of internal void percentages than all groups (p < 0.05), except Biodentine (p > 0.05).CONCLUSION: None of the filling materials were created void-free obturation in resorption cavities. Biodentine may favor its application in teeth with IRR over Angelus MTA and bulk-fill form of Total Fill BC.

Comparative evaluation of the bond strength of self-adhering and bulk-fill flowable composites to MTA Plus, Dycal, Biodentine, and TheraCal: an in vitro study

OBJECTIVES: This study aimed to compare the shear bond strength (SBS) of a self-adhering flowable composite (Dyad Flow) and a bulk-fill flowable composite (Smart Dentin Replacement [SDR]) to several pulp-capping materials, including MTA Plus, Dycal, Biodentine, and TheraCal.MATERIALS AND METHODS: Eighty acrylic blocks with 2-mm-deep central holes that were 4 mm in diameter were prepared and divided into 2 groups (n = 40 each) according to the composite used (Dyad Flow or SDR). They were further divided into 4 sub-groups (n = 10 each) according to the pulp-capping agent used. SBS was tested using a universal testing machine at a crosshead speed of 1 mm/min. Data were analyzed using 2-way analysis of variance. A p value of < 0.05 was considered to indicate statistical significance.RESULTS: A statistically significant difference (p = 0.040) was found between Dyad Flow and SDR in terms of bond strength to MTA Plus, Dycal, Biodentine, and TheraCal.CONCLUSIONS: Among the 8 sub-groups, the combination of TheraCal and SDR exhibited the highest SBS.

Efectos adversos inmunomediados por inhibidores de PD-1 / PD-1 inhibitors immune-mediated side effects

Los anticuerpos monoclonales que inhiben los puntos de control PD-1 y CTLA-4 se usan actualmente en el tratamiento del melanoma y cáncer metastásico de pulmón de células no pequeñas, entre otros. Se refiere el caso de una paciente con cáncer de pulmón en tratamiento con pembrolizumab. La paciente se presentó con edema facial y parálisis facial periférica. En el laboratorio se observó la hormona tirotrofina (TSH) elevada y se llegó al diagnóstico de hipotiroidismo por pembrolizumab. Inició tratamiento con levotiroxina con mejoría clínica. Se presenta este caso por el importante papel del dermatólogo en el manejo multidisciplinario del paciente oncológico. (AU)

Monoclonal antibodies that inhibit PD-1 and CTLA-4 control points are currently used in the treatment of melanoma and metastatic non-small cell lung cancer, among others. The case of a patient, with lung cancer being treated with Pembrolizumab. The patient was presented with facial edema and peripheral facial paralysis and in the laboratory the elevated hormone Tyrotrophin (TSH) was observed, the diagnosis of pembrolizumab hypothyroidism was reached. She started treatment with levothyroxine with clinical improvement. This case is presented by the important role of the dermatologist in the multidisciplinary management of the cancer patient. (AU)

Association between the HER2 Gene Status and the Efficacy of First-line Pemetrexed Combined with Platinum Chemotherapy in Patients with Advanced Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Human epidermal growth factor receptor 2 (HER2) is one of the driver genes of non-small cell lung cancer (NSCLC). Several studies have shown that the efficacy of pemetrexed in HER2-mutant NSCLC is controversial. The aim of this study is to investigate the efficacy of pemetrexed combined with platinum chemotherapy in patients with HER2-mutant and HER2 wild-type lung adenocarcinoma.@*METHODS@#The clinical data of 106 cases of EGFR, ALK, ROS-1, KRAS, BRAF, RET and MET-negative patients with advanced lung adenocarcinoma patients who diagnosed by histopathology in the First Affiliated Hospital of Zhengzhou University were retrospectively reviewed. The relationships between HER2 gene status, clinical characteristics and response and progression-free survival (PFS) were analyzed.@*RESULTS@#All of the 106 patients' HER2 status were determined. HER2 mutations occurred in 32 cases (30.2%), no mutations in 74 cases (69.8%). HER2 mutations were common in young, non-smoking and female patients. All patients received first-line pemetrexed and platinum-based chemotherapy. The objective response rate (ORR) and disease control rate (DCR) of patients with HER2-mutant lung adenocarcinoma were significantly higher than those without HER2 mutations (40.6% vs 14.9%, χ²=8.464, P=0.004; 93.8% vs 68.9%, χ²=6.327, P=0.012), and the difference was statistically significant. According to univariate analysis, the PFS was significantly associated with the brain metastases, maintenance chemotherapy and HER2 gene status (P0.05). Cox multivariate analysis indicated that HER2 mutation was an independent positive prognostic factor of PFS (P=0.038).@*CONCLUSIONS@#HER2-mutant lung adenocarcinoma patients with first-line pemetrexed combined with platinum chemotherapy have greater clinical benefit than HER2 wild-type patients.

A Case Report on Successful Third Challenge to the Pemetrexed-based Regimen for Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, with a 5-year survival rate of less than 15%-19%, and more than 80% of the patients with lung cancer have progressed to advanced stage (Stage IIIb-IV) when they are clearly diagnosed. The comprehensive treatment mainly based on chemotherapy as the primary form is now considered as the major therapy method for advanced NSCLC without actionable driver gene mutations. Pemetrexed plus platinum doublet as well as single-agent pemetrexed are respectively the first-line major regimens recommended by guidelines and the second-line optional regimens. Yet the third-line treatment or beyond in advanced NSCLC is not evidence-based but conducted based on patients' previous medications, which is one of the most commonly used clinical methods. As pemetrexed is a multi-target chemotherapy drug with high efficiency but low toxicity, pemetrexed re-challenge strategy in advanced NSCLC is also a reasonable choice. We report one effective individual case that adopted pemetrexed re-challenge strategy in advanced NSCLC for three times, and at the same time conduct the relevant literature review.

Comparison of the Microleakage and Shear Bond Strength to Dentine of Different Tricalcium Silicate-based Pulp Capping Materials / 대한소아치과학회지

This study evaluated the microleakage of three restorative materials and three tricalcium silicate-based pulp capping agents. The restorative materials were composite resin (CR), resin-reinforced glass ionomer cement (RMGI), and traditional glass ionomer cement (GIC) and the pulp capping agents were TheraCal LC® (TLC), Biodentine® (BD), and ProRoot® white MTA (WMTA). Additionally, shear bond strengths between the pulp-capping agents and dentine were compared.Class V cavities were made in bovine incisors and classified into nine groups according to the type of pulp-capping agent and final restoration. After immersion in 0.5% fuchsin solution, each specimen was observed with a stereoscopic microscope to score microleakage level. The crowns of the bovine incisors were implanted into acrylic resin, cut horizontally, and divided into three groups. TLC, BD and WMTA blocks were applied on dentine, and the shear bond strengths were measured using a universal testing machine.The microleakage was lowest in TLC + GIC, TLC + RMGI, TLC + CR, and BD + GIC groups and highest in WMTA + RMGI and WMTA + CR groups. The shear bond strength of BD group was the highest and that of WMTA group was significantly lower than the others.

A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). MATERIALS AND METHODS: We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. RESULTS: A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. CONCLUSION: The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.

Effects of various root canal sealers on tooth discoloration and internal bleaching / 대한치과재료학회지

There are several causes of tooth discoloration following root canal treatment. In this study, we evaluated the effects of sealers on tooth discoloration and internal bleaching. Twenty-four teeth were divided into 4 groups: control group, AH plus, Endosequece BC, and MTA fillapex group. Root canal filling was performed using each sealer conventionally and non-vital bleaching was performed with sodium perborate. The L, a, and b values were measured using Vita easyshade. Tooth discoloration after root canal treatment occurs irrespective of the type of sealers and may cause discoloration with only gutta-percha cone. The effect of non-vital bleaching following the use of calcium silicate-based sealers such as Endosequece BC and MTA fillapex was higher than that of AH plus. Therefore, it needs careful use of sealers in endodontics and calcium silicate-based sealers have advantages of bleaching in case of discolored tooth.

Discoloration and radiopacity of white mineral trioxide aggregate with various radiopacifiers / 대한치과재료학회지

The use of the mineral trioxide aggregate (MTA) has been expanded as the material can be applied on various treatment of endodontic care, which also has many advantages including bioactivity. Still, the discolorations of the materials have been presented as a concern related to esthetic appearances, which is caused by the presence of radiopacifiers. Therefore, the aim of this study was to investigate the color stability and radiopacity of white MTA with various radiopacifiers. Four different radiopacifiers [bismuth oxide (BM), calcium tungstate (CT), barium oxide (BO), and zirconium oxide (ZO)] were used. The radiopacity was tested according to ISO 6876, and the color change before and after immersing in a 5% hypochlorite solution was tested using a spectrophotometer. The group with no radiopacifier (NR) was used as a negative control and ProRoot MTA (PR) was used as the commercial control. The immersion of the PR and BM in sodium hypochlorite resulted in a dark brown discoloration, in which the values were higher than the rest of the group (p0.05). In terms of the radiopacity, the NR showed the lowest value as expected (p<0.05). Meanwhile, the BM showed the highest value (p<0.05), followed by PR and BO (p<0.05). The NR showed the lowest radiopacity values. The result of this study will be useful for future development of MTA that would have clinically adequate radiopacity with minimum discoloration.

Coronal tooth discoloration induced by regenerative endodontic treatment using different scaffolds and intracanal coronal barriers: a 6-month ex vivo study

OBJECTIVE: The aim of this study was to evaluate discoloration of teeth undergoing regenerative endodontic procedures (REPs) using blood clot or platelet-rich fibrin (PRF) as the scaffolds and different calcium silicate-based materials as the intracanal coronal barriers in an ex vivo model. MATERIALS AND METHODS: Forty-eight bovine incisors were prepared and disinfected using 1 mg/mL double antibiotic paste (DAP). The specimens were then randomly divided into 2 groups (n = 24) according to the scaffolds (blood or PRF). After placement of scaffolds each group was divided into 2 subgroups (n = 12) according to the intracanal coronal barriers (ProRoot MTA or Biodentine). The pulp chamber walls were sealed with dentin bonding agent before placement of DAP and before placement of scaffolds. The color changes (∆E) were measured at different steps. The data were analyzed using 2-way analysis of variance. RESULTS: Coronal discoloration induced by DAP was not clinically perceptible (ΔE ≤ 3.3). Regarding the type of the scaffold, coronal discoloration was significantly higher in blood groups compared with PRF groups at the end of REP and after 1 month (p 0.05). Considering the type of intracanal coronal barrier, no significant difference existed between ProRoot MTA and Biodentine (p > 0.05). CONCLUSIONS: With sealing the dentinal tubules of pulp chamber with a dentin bonding agent and application of DAP as an intracanal medicament, coronal color change of the teeth following the use of PRF and blood sealed with either ProRoot MTA or Biodentine was not different at 6-month follow-up.

Effect of calcium hydroxide on inflammatory root resorption and ankylosis in replanted teeth compared with other intracanal materials: a review

Calcium hydroxide (CH) is the gold-standard intracanal dressing for teeth subjected to traumatic avulsion. A common complication after the replantation of avulsed teeth is root resorption (RR). The current review was conducted to compare the effect of CH with that of other intracanal medications and filling materials on inflammatory RR and replacement RR (ankylosis) in replanted teeth. The PubMed and Scopus databases were searched through June 2018 using specific keywords related to the title of the present article. The materials that were compared to CH were in 2 categories: 1) mineral trioxide aggregate (MTA) and endodontic sealers as permanent filling materials for single-visit treatment, and 2) Ledermix, bisphosphonates, acetazolamide, indomethacin, gallium nitrate, and enamel matrix-derived protein (Emdogain) as intracanal medicaments for multiple-visit management of avulsed teeth prior to the final obturation. MTA can be used as a single-visit root filling material; however, there are limited data on its efficacy due to a lack of clinical trials. Ledermix and acetazolamide were comparable to CH in reducing RR. Emdogain seems to be an interesting material, but the data supporting its use as an intracanal medication remain very limited. The conclusions drawn in this study were limited by the insufficiency of clinical trials.