RESUMO
Aflibercept (AFL) plus FOLFIRI prolongs overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, there is limited evidence on the efficacy and safety of AFL plus FOLFIRI previously treated with anti-epidermal growth factor receptor (EGFR) agents. Therefore, we conducted a prospective open-label phase II trial evaluating the efficacy and safety of AFL plus FOLFIRI in Japanese patients with mCRC failing a prior oxaliplatin-based chemotherapy plus an anti-EGFR agent. AFL (4 mg/kg iv) followed by FOLFIRI (irinotecan 180 mg/m2, leucovorin 200 mg/m2 iv, bolus 5-fluorouracil [5-FU] 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) was given every 2 weeks until progression or unacceptable toxicities. The primary endpoint was progression-free survival (PFS) rate at 6 months. Forty three patients were enrolled between November 2019 and October 2022. The primary endpoint was met: 6-month PFS rate was 58.8% (90% confidence interval [CI], 45.7%-72.0%). Median PFS and OS were 7.3 months (95% CI, 5.5-11.0 months) and 18.8 months (95% CI, 12.9-26.6 months), respectively. The overall response rate was 20.9% (95% CI, 10.0-36.0%) and disease control rate was 88.4% (95% CI, 74.9-96.1%). The main grade ≥3 adverse events included hypertension (62.8%), neutropenia (55.8%), leukopenia (25.6%), febrile neutropenia (11.6%), fatigue (9.3%), anorexia (9.3%), proteinuria (9.3%), and diarrhea (7.0%). No deaths and no new safety signals with a causal relation to the study treatment were observed. This study suggests that AFL plus FOLFIRI shows a high response rate and a manageable safety profile in Japanese patients with mCRC who failed prior oxaliplatin-based chemotherapy plus an anti-EGFR agent.
RESUMO
OBJECTIVE: The incidence of periprosthetic fractures after total hip arthroplasty using a short tapered-wedge stem is high. Callus formation preceding this fracture, which indicates postoperative stress fracture around the stem, has been reported. However, previous studies on postoperative callus are limited. Hence, the current study aimed to evaluate the prevalence and risk factors of postoperative callus after total hip arthroplasty with a short tapered-wedge stem. MATERIALS AND METHODS: This retrospective study included 127 patients who underwent total hip arthroplasty using a cementless short tapered-wedge stem. The depth of stem insertion was measured as the distance from the lateral corner of the stem to the most medial point of the lesser trochanter along the body axis. Postoperative callus was defined as a bridging callus on the lateral femoral cortex at the distal end of the porous coating of the stem. Plain radiography was performed before surgery and immediately and at 1, 3, and 6 months after surgery to assess postoperative callus. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for PC. RESULTS: In total, 60 (47.2%) of 127 patients presented with postoperative callus. Multivariate logistic regression analysis with postoperative callus as the dependent variable revealed that the stem depth at 1 month after total hip arthroplasty (odds ratio, 1.14; 95% confidence interval, 1.04-1.24, p = 0.002) was a significant and independent risk factor of postoperative callus. CONCLUSION: Deep insertion of a short tapered-wedge stem is a risk factor for postoperative callus.
RESUMO
BACKGROUND: Capecitabine plus oxaliplatin (CapeOX) is a standard treatment option for advanced gastric cancer (AGC). We conducted a prospective multicenter phase II study to evaluate the efficacy and safety of CapeOX as a first-line therapy for AGC in older patients. METHODS: Chemotherapy-naive patients aged ≥ 70 years with AGC were eligible. Initial treatment comprised capecitabine (2000 mg/m2 on days 1-14) and oxaliplatin (130 mg/m2 on day 1) every 3 weeks. After the initial feasibility assessment, the dose was reduced considering toxicity (capecitabine, 1500 mg/m2 on days 1-14; and oxaliplatin, 100 mg/m2 on day 1 every 3 weeks). The primary endpoint was overall survival (OS). RESULTS: In total, 108 patients were enrolled, of whom 104 were evaluated. Thirty-nine patients received the original-dose treatment, whereas 65 received the reduced-dose treatment. The median OS, progression-free survival (PFS), and time to treatment failure (TTF) were 12.9 (95% CI 11.6-14.8), 5.7 (95% CI 5.0-7.0), and 4.3 (95% CI 3.9-5.7) months, respectively, for all patients; 13.4 (95% CI 9.5-16.0), 5.8 (95% CI 4.1-7.8), and 5.3 (95% CI 3.5-7.2) months in the original-dose group; and 12.8 (95% CI 11.3-15.3), 5.7 (95% CI 4.4-7.0), and 4.1 (95% CI 3.7-5.7) months in the reduced-dose group. The most common grade 3/4 toxicities were neutropenia (17.9%), anemia (12.8%), and thrombocytopenia (12.8%) in the original-dose group and neutropenia (13.8%) and anorexia (12.3%) in the reduced-dose group. CONCLUSIONS: These findings demonstrate CapeOX's efficacy and safety in older AGC patients.
Assuntos
Neutropenia , Neoplasias Gástricas , Humanos , Idoso , Capecitabina , Oxaliplatina/uso terapêutico , Estudos Prospectivos , Tóquio , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia/induzido quimicamente , Neutropenia/tratamento farmacológico , FluoruracilaRESUMO
BACKGROUND: Accurate identification of the cricothyroid membrane is crucial for successful cricothyrotomy; however, a manoeuvre that helps identify it both accurately and quickly remains unclear. The effectiveness of the so-called 'bottom-up manoeuvre' has never been investigated. This study aimed to examine whether the bottom-up manoeuvre is as rapid and accurate as the conventional 'top-down manoeuvre' at identifying the cricothyroid membrane. METHODS: This study was a prospective randomised cross-over trial conducted at an academic medical centre between 2018 and 2019. Fifth-year medical students participated. The students were trained in the use of either the top-down manoeuvre or the bottom-up manoeuvre first. Each student subsequently performed the technique once on a volunteer. The students were then taught and practiced the other manoeuvre as well. The accuracy of cricothyroid membrane identification and the time taken by successful participants only were measured and compared between the manoeuvres using equivalence tests with two one-sided tests. RESULTS: A total of 102 medical students participated in this study and there was no missing data. The accuracy of identification and time required for success were similar between the top-down manoeuvre and the bottom-up manoeuvre (65.7% vs. 70.6%, taking 13.8 s [interquartile range (IQR): 9.4-17.5] vs. 15.5 s [IQR: 11.5-19.9], respectively). The success rate was statistically equivalent (rate difference, 4.9%; 90% confidence interval [CI], -5.8 to 15.6; equivalence margin, -20.0 to 20.0). The time required for success was also statistically equivalent (median difference, 1.7 s; 90% CI, -0.2 to 3.3; equivalence margin, -4.0 to 4.0). CONCLUSION: Among students first trained in both manoeuvres for identifying the cricothyroid membrane, the speed and accuracy of identification were similar between those using the bottom-up manoeuvre and those using the top-down manoeuvre.
Assuntos
Cartilagem Cricoide , Cartilagem Tireóidea , Humanos , Estudos Cross-Over , Estudos ProspectivosRESUMO
The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.
RESUMO
BACKGROUND: Although initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at high risk of bleeding. METHODS: In this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. RESULTS: Of the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who experienced MB or CRNMB recovered. CONCLUSIONS: The risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.
Assuntos
Neoplasias Gastrointestinais , Trombose , Humanos , Inibidores do Fator Xa/efeitos adversos , Estudos Prospectivos , Estudos de Viabilidade , População do Leste Asiático , Anticoagulantes/efeitos adversos , Hemorragia/tratamento farmacológico , Heparina , Trombose/prevenção & controle , Trombose/induzido quimicamente , Neoplasias Gastrointestinais/complicações , Neoplasias Gastrointestinais/tratamento farmacológicoRESUMO
Background: The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. Methods: FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. Discussion: There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. Clinical trial registration: Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
RESUMO
BACKGROUND: Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. RESULTS: Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%-41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. CONCLUSION: Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.
Assuntos
Neoplasias Gástricas , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Irinotecano/uso terapêutico , Neoplasias Gástricas/patologia , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular , RamucirumabRESUMO
DNA methylation status correlates with clinical outcomes of anti-epidermal growth factor receptor (EGFR) treatment. There is a strong need to develop a simple assay for measuring DNA methylation status for the clinical application of drug selection based on it. In this study, we collected data from 186 patients with metastatic colorectal cancer (mCRC) who had previously received anti-EGFR treatment. We modified MethyLite to develop a novel assay to classify patients as having highly methylated colorectal cancer (HMCC) or low-methylated colorectal cancer (LMCC) based on the methylation status of 16 CpG sites of tumor-derived genomic DNA in the development cohort (n = 30). Clinical outcomes were then compared between the HMCC and LMCC groups in the validation cohort (n = 156). The results showed that HMCC had a significantly worse response rate (4.2% vs 33.3%; P = .004), progression-free survival (median: 2.5 vs 6.6 mo, P < .001, hazard ratio [HR] = 0.22), and overall survival (median: 5.6 vs 15.5 mo, P < .001, HR = 0.23) than did LMCC in patients with RAS wild-type mCRC who were refractory or intolerable to oxaliplatin- and irinotecan-based chemotherapy (n = 101). The DNA methylation status was an independent predictive factor and a more accurate biomarker than was the primary site of anti-EGFR treatment. In conclusion, our novel DNA methylation measurement assay based on MethyLight was simple and useful, suggesting its implementation as a complementary diagnostic tool in a clinical setting.
Assuntos
Neoplasias Colorretais/genética , Metilação de DNA , Receptores ErbB/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Ilhas de CpG/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas p21(ras)/genética , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Angiogenesis inhibitors (AIs) combination with cytotoxic chemotherapy is a promising treatment for patients with colorectal cancer (CRC). Aflibercept (AFL) is an option for second-line treatment of CRC, according to the 'VELOUR' trial. Currently, we can choose from three AIs, including bevacizumab, ramucirumab, and AFL. Different AIs can be used in subsequent treatment because of their distinctive mechanisms of action. We addressed the uncertainty regarding AFL efficacy and safety in heavily-treated patients by comparing outcomes of survival treatment with second-line treatment. AIM: To determine and compare the efficacy and safety profiles of AFL in the second-line and salvage therapy settings. METHODS: Clinical data of 41 patients with advanced CRC who received intravenous AFL combined with the folinic acid-fluorouracil-irinotecan (FOLFIRI) regimen were collected retrospectively from six institutions in Japan, for the period from May 2017 to March 2019. Patient characteristics collected included age, sex, tumor location, RAS and RAF status, metastatic sites, number of previous treatment cycles, therapeutic response, adverse events, duration of previous AI treatment, and survival time. The end points were time to AFL treatment failure (aTTF) and median survival time post-AFL (aMST). Statistical analyses were performed to compare the efficacy and safety in the second-line setting with those of the salvage therapy setting, which was defined as the days since the end of second-line therapy. RESULTS: All 41 patients who received AFL + FOLFIRI for advanced CRC had metastatic or unresectable cancer. Twenty-two patients received AFL in the second-line setting and nineteen in the salvage therapy setting. The patient characteristics were similar in the two groups, except for two factors. The median duration of the previous AI administration was shorter in the second-line patients compared with that in the salvage therapy patients (144 d vs 323 d, P = 0.006). In the second-line and salvage therapy groups, the objective response rates were 11% and 0%, respectively (P = 0.50), and the disease control rates were 53% and 50%, respectively (P = 1.00). In the second-line and salvage therapy groups, the aTTF (123 d vs 71 d, respectively), aMST (673 d vs 396 d, respectively), and incidence of adverse events of grade 3 [8 (36%) vs 9 (47%)] were not significantly different between the two groups. CONCLUSION: AFL can be used to treat advanced CRC patients, with a similar safety and efficacy in the salvage therapy setting as in the second-line setting.
RESUMO
A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.
Assuntos
Úlcera Duodenal/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Úlcera Péptica Hemorrágica/tratamento farmacológico , Inibidores da Bomba de Prótons/uso terapêutico , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/tratamento farmacológico , Adolescente , Adulto , Idoso , Biópsia/métodos , Úlcera Duodenal/diagnóstico , Feminino , Hemostase Endoscópica/métodos , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
Background Adolescent idiopathic scoliosis (AIS) is a potentially progressive deformity, and early detection is crucial for timely intervention. However, the methods and criteria justifying screening for pediatric scoliosis remain controversial. We have, therefore, independently developed a Digital Moiré (DM) as a tool for scoliosis screening. The purpose of this study was to assess the usefulness of DM for scoliosis screening. Methods From March 2016 to March 2017, 126 patients (18 boys, 108 girls, mean age: 13.2 ± 2.2 years) with AIS underwent radiographic imaging of their whole spine. We tested the accuracy and reliability of DM by categorizing the examination results as Class 0 (no abnormality), Class 1 (return visit in one year), and Class 2 (further examination needed) and determined the distribution of the population by Cobb angle. The intra/inter-rater reliability and receiver operating characteristic (ROC) analyses were used to categorize the patients with positive findings into Class 1 or 2. Results Regarding the population distribution per Cobb angle in each of the distributions, 11 patients (8.7%) were Class 0, of which nine and two patients had Cobb angle ≤ 10 ° and > 10 °, respectively. There were 20 (15.9% ) Class 1 cases, of which 17 and three had Cobb angle ≤ 10 ° and > 10 °, respectively. Of the 95 (75.4%) Class 2 cases, five and 90 had a Cobb angle of ≤ 10 ° and > 10 °, respectively. The receiver operating characteristic (ROC) analysis of patients with positive findings showed that the area under the curve (AUC), sensitivity, specificity, and false-positive rate were 0.76, 0.98, 0.53, and 0.47, respectively, when predicting Cobb angle > 10°. Intra-rater and inter-rater reliability were 0.73 and 0.70, respectively. Conclusions This study demonstrated the usefulness of DM for determining whether a child with AIS requires a follow-up observation such as radiograph. Our findings suggest that the novel DM shows high accuracy and reliability for scoliosis screening.
RESUMO
Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignant tumor. It is a refractory tumor and the median overall survival is very short. We report two autopsy cases of DSRCT, both of which were already advanced and metastasized at the first medical examination. Both cases showed typical DSRCT findings in terms of localization of the lesions, histopathology and genetics, but the rate of disease progression was quite different. Survival after initial symptoms in Case 1 was only 12 months. On the other hand, survival after primary hospitalization in Case 2 was 42 months. The Case 2 patient initially received chemotherapy for advanced pancreatic carcinoma, because a nodule of the pancreatic tail was found on computed tomography (CT) scan. After chemotherapy, tumor regression was observed on CT scan. It is thus implied that adoption of the regimen for pancreatic carcinoma might have been one of reasons of the long survival in Case 2.
Assuntos
Tumor Desmoplásico de Pequenas Células Redondas/diagnóstico por imagem , Proteínas de Fusão Oncogênica/genética , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Autopsia , Tumor Desmoplásico de Pequenas Células Redondas/tratamento farmacológico , Tumor Desmoplásico de Pequenas Células Redondas/genética , Tumor Desmoplásico de Pequenas Células Redondas/patologia , Humanos , Hibridização in Situ Fluorescente , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X , Translocação Genética/genética , Neoplasias PancreáticasRESUMO
Immune checkpoint inhibitors may have different clinical effects compared with conventional anticancer drugs. An 85-year-old male received chemotherapy for recurrent gastric cancer. As liver metastasis progressed, nivolumab was introduced as a fourth line treatment. Progression of liver metastasis in size was observed in CT after 3 courses of nivolumab therapy. Nivolumab treatment was discontinued, because the general condition of the patient also worsened. However, his general condition improved as hepatobiliary enzyme levels, inflammatory response, and tumor markers improved. Liver metastasis was shrinking on the image, so we resumed nivolumab therapy. To the authors' knowledge, this is the first case of pseudoprogression undergoing immunotherapy for gastric cancer. In this case, the antitumor effect was exhibited in a delayed manner and the tumor shrinkage was obtained.
Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/diagnóstico por imagem , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasias Gástricas/patologia , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
A 32-year-old woman was found to have a gastric adenocarcinoma with multiple bone metastases. Chemotherapy in the first, second and third-line was not effective. Blood examinations showed disseminated intravascular coagulation(DIC)at the end of the second-line chemotherapy. The fourth-line chemotherapy, infusional 5-fluorouracil and levofolinate calcium was performed. This resulted in a good response for DIC. This palliative therapy was effective and safety.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Coagulação Intravascular Disseminada/etiologia , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Adulto , Feminino , Fluoruracila/administração & dosagem , Gastrectomia , Humanos , Levoleucovorina/administração & dosagem , Neoplasias Gástricas/complicações , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoAssuntos
Descompressão Cirúrgica/efeitos adversos , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Paraplegia/etiologia , Compressão da Medula Espinal/etiologia , Fusão Vertebral/efeitos adversos , Adulto , Descompressão Cirúrgica/métodos , Seguimentos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Ossificação do Ligamento Longitudinal Posterior/etiologia , Paraplegia/diagnóstico por imagem , Doenças Raras , Medição de Risco , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/cirurgia , Fusão Vertebral/métodos , Vértebras Torácicas/fisiopatologia , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Luta Romana/lesõesRESUMO
Glioblastoma (GBM) is the most lethal and aggressive adult brain tumor, requiring the development of efficacious therapeutics. Towards this goal, we screened five genetically distinct patient-derived brain-tumor initiating cell lines (BTIC) with a unique collection of small molecule epigenetic modulators from the Structural Genomics Consortium (SGC). We identified multiple hits that inhibited the growth of BTICs in vitro, and further evaluated the therapeutic potential of EZH2 and HDAC inhibitors due to the high relevance of these targets for GBM. We found that the novel SAM-competitive EZH2 inhibitor UNC1999 exhibited low micromolar cytotoxicity in vitro on a diverse collection of BTIC lines, synergized with dexamethasone (DEX) and suppressed tumor growth in vivo in combination with DEX. In addition, a unique brain-penetrant class I HDAC inhibitor exhibited cytotoxicity in vitro on a panel of BTIC lines and extended survival in combination with TMZ in an orthotopic BTIC model in vivo. Finally, a combination of EZH2 and HDAC inhibitors demonstrated synergy in vitro by augmenting apoptosis and increasing DNA damage. Our findings identify key epigenetic modulators in GBM that regulate BTIC growth and survival and highlight promising combination therapies.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Glioblastoma/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Piridonas/uso terapêutico , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dexametasona/uso terapêutico , Sinergismo Farmacológico , Quimioterapia Combinada , Epigênese Genética , Inibidores de Histona Desacetilases/farmacologia , Humanos , Camundongos , Camundongos SCID , Terapia de Alvo Molecular , Piridonas/farmacologia , Bibliotecas de Moléculas Pequenas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report the case of a patient with advanced colon cancer receiving oxaliplatin-based chemotherapy that was able to continue systemic chemotherapy by performing mild partial splenic embolization (PSE) for thrombocytopenia caused by splenomegaly due to oxaliplatin. Mild PSE may be useful for thrombocytopenia due to splenomegaly in cancer patients because it provides more treatment opportunities.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Embolização Terapêutica/métodos , Compostos Organoplatínicos/efeitos adversos , Baço , Trombocitopenia/induzido quimicamente , Trombocitopenia/terapia , Adulto , Feminino , Humanos , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Esplenomegalia/induzido quimicamente , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the safety and efficacy of a modified administration schedule of docetaxel, cisplatin, and fluorouracil (mDCF)in patients with advanced gastric cancer with gastrointestinal stenosis in clinical practice. METHODS: In the chemotherapy-naïve patients who had metastatic or recurrent histologically confirmed gastric cancer, docetaxel(40mg/m2), levofolinate(200mg/m / / / 2), fluorouracil(400mg/m2)on day 1, fluorouracil 1,000 mg/m2d-2 days intravenous continuous in fusion beginning on day 1, and cisplatin(40mg/m2)on day 3 was administered every 2 weeks. RESULTS: Six patients received mDCF therapy. In 5 patients with measurable disease, the overall response rate was 86%. Median progression-free survival was 310 days and median overall survival was 599 days. Symptom improvement after the first cycle of mDCF was obtained in all patients. Grade 3 or 4 leukopenia and neutropenia were observed in 2(33%)and 6(100%)patients, respectively. There were no treatment-related deaths. CONCLUSION: mDCF seems to be active against metastatic and recurrent gastric cancer with gastrointestinal stenosis. Further study is needed to confirm the efficacy and safety of mDCF regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Obstrução da Saída Gástrica/etiologia , Obstrução Intestinal/etiologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Idoso , Cisplatino/administração & dosagem , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Gastroenteropatias , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Neoplasias Gástricas/complicações , Taxoides/administração & dosagemRESUMO
STUDY DESIGN: A retrospective investigation of the retrodental mass secondary to rheumatoid arthritis (RA). OBJECTIVE: To propose a new classification of the retrodental mass in RA, and to evaluate their resorption processes and surgical procedures. SUMMARY OF BACKGROUND DATA: The retrodental mass secondary to RA has long been recognized as pannus formation. It is also known that pannus will disappear or radically reduce after stabilization of the atlantoaxial segment. The past reports, however, leave unanswered the following question; are there other types of mass with significantly different degeneration processes from the pannus? The need for anterior transoral decompression is still controversial. METHODS: Eleven patients with retrodental masses in RA were retrospectively analyzed. They underwent posterior fusion without decompression for atlantoaxial subluxation and occipitocervical fusion with decompressive laminectomy of the atlas for vertical subluxation. All patients had neurological, radiologic, and magnetic resonance imaging (MRI) evaluations both before and after surgery. MRI study was performed preoperatively and at 1-month interval after surgery until the mass had disappeared or stopped further reduction. RESULTS: This study identified 3 distinctive types in the rheumatoid retrodental mass on MRI. Type 1 displayed high intensity on T2 and low intensity on T1-weighted MRI or the pattern specific to pannus. Type 2 was identified with low intensity on T2-weighted MRI or pattern specific to pseudotumor. Type 3 displayed a combination of high and low intensity on T2-weighted images or indication that the mass was the mixture of pannus and pseudotumor. All the masses of types 1 and 3 disappeared within 1 month of surgery. The process in type 2 was found a few months slower. In all 11 cases, myelopathy improved postoperatively to the status before the emergence of the symptom. CONCLUSIONS: This article recognized 3 distinctive types of the retrodental mass in RA; type 1 (pannus), type 2 (pseudotumor), type 3 (mixed). It further concludes in all types of the retrodental mass associated with atlantoaxial subluxation secondary to RA, posterior fusion without decompression can achieve improvement of the myelopathy. In type 2 associated with vertical subluxation, on balance between calculable benefits and high risks of anterior transoral decompression, the authors prefer to opt for occipitocervical fusion with decompressive laminectomy of the atlas.