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1.
Artigo em Inglês | MEDLINE | ID: mdl-32736865

RESUMO

OBJECTIVE: The prognostic significance of tumor size in thymic epithelial tumors (TETs) has not been fully evaluated. We aimed to clarify the prognostic value of tumor size in limited-stage and advanced-stage TETs. METHODS: Clinical records of patients with completely resected TETs were retrospectively collected from 4 tertiary centers between January 2000 and February 2013. Information on the Masaoka-Koga stage was available for 1215 patients (M-K group), and 433 patients were classified according to the eighth edition of the Tumor-Node-Metastasis staging system (TNM group). Limited-stage and advanced-stage TETs were defined according to whether they were confined within the surrounding fatty tissues without invasion. The optimal cutoff value was selected using a maximally selected log-rank statistic. RESULTS: The median tumor size was 6.0 ± 2.8 cm in the M-K group and 6.5 ± 3.0 cm in the TNM group. In the multivariable analysis, tumor size had a significant effect on both overall survival (P = .003) and recurrence-free survival (P < .001) for limited-stage tumors (M-K stage I or II or TNM stage I), but not for advanced-stage tumors (M-K stage III or IV or TNM stage II-IV; P = .349 for overall survival and P = .439 for recurrence-free survival). The optimal cutoff value for tumor size was >5.5 cm for both overall survival and recurrence-free survival in limited-stage TETs. CONCLUSIONS: Tumor size is an independent prognostic factor in patients with completely resected limited-stage TETs and a cutoff value >5.5 cm might help clinicians enact proper treatment strategies and surveillance.

2.
Cancer Res Treat ; 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32599990

RESUMO

Purpose: The aim of this study was to evaluate the ability of sequential 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) after one cycle of neoadjuvant chemotherapy (NAC) to predict chemotherapy response before interval debulking surgery (IDS) in advanced-stage ovarian cancer patients. Material and Methods: Forty consecutive patients underwent 18F-FDG-PET/CT at baseline and after one cycle of NAC. Metabolic responses were assessed by quantitative decrease in the maximum standardized uptake value (SUVmax) with PET/CT. Decreases in SUVmax were compared with cancer antigen 125 (CA-125) level before IDS, response rate by Response Evaluation Criteria in Solid Tumors criteria before IDS, residual tumor at IDS, and chemotherapy response score (CRS) at IDS. Results: A 40% cut-off for the decrease in SUVmax provided the best performance to predict CRS 3 (compete or near-complete pathologic response), with sensitivity, specificity, and accuracy of 81.8%, 72.4%, and 72.4%, respectively. According to this 40% cut-off, there were 17 (42.5%) metabolic responders (≥ 40%) and 23 (57.5%) metabolic non-responders (< 40%). Metabolic responders had higher rate of CRS 3 (52.9% vs. 8.7%, p=0.003), CA-125 normalization (< 35 U/mL) before IDS (76.5% vs. 39.1%, p=0.019), and no residual tumor at IDS (70.6% vs. 31.8%, p=0.025) compared with metabolic non-responders. There were significant associations with progression-free survival (p=0.021) between metabolic responders and non-responders, but not overall survival (p=0.335). Conclusion: Early assessment with 18F-FDG-PET/CT after one cycle of NAC can be useful to predict response to chemotherapy before IDS in patients with advanced-stage ovarian cancer.

3.
J Korean Med Sci ; 35(28): e261, 2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32686374

RESUMO

BACKGROUND: Indeterminate pulmonary nodules (IPN) suspected for early stage lung cancer mandate accurate diagnosis. Both percutaneous needle biopsy (PCNB) and surgical biopsy (SB) are valuable options. The present study aimed to compare the efficacy and cost-effectiveness between PCNB and SB for IPN suspected for early stage lung cancer. METHODS: During January-November 2018, patients who underwent operation for IPN suspected for early stage lung cancer (SB group, n = 245) or operation after PCNB (PCNB group, n = 113) were included. Patient-level cost data were extracted from medical bills from the institution. Propensity score matching was performed between the two groups from a retrospectively-collected database. RESULTS: Fifteen patients (11.5%) had complications after PCNB; thirteen (11.5%) were not confirmed to have lung cancer through PCNB but underwent operation for IPN. In SB group, 172 (70.2%) and 7 (2.9%) patients underwent wedge resection and segmentectomy for SB, respectively; 66 patients (26.9%) underwent direct lobectomy without SB. After propensity score matching, 58 paired samples were produced. Most patients in PCNB group were admitted twice (n = 55, 94.8%). The average hospital stay was longer in PCNB group (12.9 ± 5.3 vs. 7.3 ± 3.0, P < 0.001). Though the cost of the operation was comparable (USD 12,509 ± 2,909 vs. 12,669 ± 3,334; P = 0.782), the total cost was higher for PCNB group (USD 14,403 ± 3,085 vs. 12,669 ± 3,334; P = 0.006). The average subcategory cost, which increases proportional to hospital stay, was higher in PCNB group, whereas the cost of operation and surgical materials were comparable between the two groups. CONCLUSION: Lung cancer operation following SB for IPN was associated with lesser cost, shorter hospital stays, and lesser admission time than lung cancer operation after PCNB. The increased cost and longer hospital stay appear largely related to the admission for PCNB.

4.
Yonsei Med J ; 61(7): 606-613, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32608204

RESUMO

PURPOSE: Data on the distribution and impact of panel reactive antibodies (PRA) and donor specific antibodies (DSA) before lung transplantation in Asia, especially multi-center-based data, are limited. This study evaluated the prevalence of and effects of PRA and DSA levels before lung transplantations on outcomes in Korean patients using nationwide multicenter registry data. MATERIALS AND METHODS: This study included 103 patients who received a lung transplant at five tertiary hospitals in South Korea between March 2015 and December 2017. Mortality, primary graft dysfunction (PGD), and bronchiolitis obliterans syndrome (BOS) were evaluated. RESULTS: Sixteen patients had class I and/or class II PRAs exceeding 50%. Ten patients (9.7%) had DSAs with a mean fluorescence intensity (MFI) higher than 1000, six of whom had antibodies with a high MFI (≥2000). DSAs with high MFIs were more frequently observed in patients with high-grade PGD (≥2) than in those with no or low-grade (≤1) PGD. In the 47 patients who survived for longer than 9 months and were evaluated for BOS after the transplant, BOS was not related to DSA or PRA levels. One-year mortality was more strongly related to PRA class I exceeding 50% than that under 50% (0% vs. 16.7%, p=0.007). CONCLUSION: Preoperative DSAs and PRAs are related to worse outcomes after lung transplantation. DSAs and PRAs should be considered when selecting lung transplant recipients, and recipients who have preoperative DSAs with high MFI values and high PRA levels should be monitored closely after lung transplantation.

5.
Int J Gynecol Cancer ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32675054

RESUMO

INTRODUCTION: Subcutaneous negative pressure wound drains have been used to reduce wound complication rates in various surgical procedures. However, research on the benefits of subcutaneous drains on wound healing after ovarian cancer surgery is limited. The aim of this study was to assess the effects of subcutaneous negative pressure drains on wound healing after abdominal surgery for ovarian cancer. METHODS: Patients who underwent surgery with a midline incision for ovarian cancer between February 2015 and May 2019 were retrospectively examined. Patients were divided into two groups according to the presence (group 1; n=99) or absence (group 2; n=213) of subcutaneous wound drains. The primary endpoint was the incidence of wound complications within 8 weeks after abdominal surgery. The secondary endpoints were time interval from surgery to adjuvant chemotherapy and survival. RESULTS: Patients in group 1 were older (mean 58.5 vs 55.4 years; p=0.02), and had higher rates of previous abdominal surgery (66.7% vs 47.9%; p=0.002), bowel surgery (47.5% vs 34.3%; p=0.026), and had a high surgical complexity score (53.5% vs 33.8%; p<0.001) compared with patients in group 2. Median body mass index was not different between the two groups: group 1, 22.9 kg/m2 (range 16.0 to 33.3) and group 2, 22.8 kg/m2 (range 16.4 to 37.5) (p=0.858). A higher rate of clear wound healing (82.8% vs 71.8%; p=0.036) and a lower rate of seroma formation (6.1% vs 16.0%; p=0.015) were observed in group 1 compared with group 2. After multivariate analysis, subcutaneous wound drain placement was identified as an independent predictive factor for preventing wound complications (adjusted odds ratio 0.43; 95% confidence interval 0.21 to 0.87). Time interval from surgery to adjuvant treatment was significantly longer in patients with wound complications than in those with clear wound healing (mean 23.6 vs 19.2 days; p=0.003). Kaplan-Meier analysis, however, showed no significant differences in progression free or overall survival between the two groups (p=0.35 and p=0.96, respectively). CONCLUSION: The prophylactic use of subcutaneous negative pressure drains after abdominal surgery for ovarian cancer significantly reduced the incidence of wound complications in this study.

6.
Mod Pathol ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641744

RESUMO

Gastric-type mucinous carcinoma (GAS) is a recently established variant of endocervical mucinous adenocarcinoma that is characterized as being unrelated to HPV and having aggressive behavior and chemoresistance. GAS has a distinct morphology resembling nonneoplastic gastric glands or pancreaticobiliary adenocarcinoma, and their possible genetic similarity has been posed. In this study, next-generation sequencing was performed in 21 GAS cases using a customized panel including 94 cancer-associated genes. A total of 54 nonsynonymous somatic mutations were detected with an average mutation rate of 2.6 per lesion (range: 0-9). The most frequently mutated gene was TP53 (11/21, 52.4%), followed by STK11, HLA-B, PTPRS (4/21, 19.0%), FGFR4 (3/21, 14.3%), GNAS, BRCA2, ELF3, ERBB3, KMT2D, SLX4 (2/21, 9.5%), CDH1, EPCAM, KRAS, MLH1, RNF43, SNAI1, TWIST1, ZEB1, ZEB2, and so on (1/21, 4.8%). The mutated genes were mostly involved in signal transduction, DNA damage repair, and epithelial-mesenchymal transition (EMT). Correlation of TP53 mutation and p53 protein expression demonstrated that 31.3% with abnormal p53 expression harbored wild-type TP53. Compared to genetic features of gastric and pancreaticobiliary adenocarcinoma, TP53 mutations were frequent in both GAS and gastrointestinal adenocarcinoma. While KMT2D, ERBB3, and RNF43 mutations were shared between GAS and gastric adenocarcinoma, highly mutated genes in pancreatic ductal adenocarcinoma such as KRAS, SMAD4, and CDKN2A were rarely mutated in GAS. Of frequently mutated genes in cholangiocarcinoma, BAP1 and HLA-B were identified in GAS. Frequent EMT-related gene mutations suggested a possible role of EMT-related pathways in tumor dissemination and chemoresistance of GAS. In addition, GAS shared some genetic features with gastrointestinal adenocarcinoma. These findings provide a clue in understanding the biological basis of GAS.

7.
Radiology ; 296(1): 216-224, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32396042

RESUMO

Background Deep learning models have the potential for lung cancer prognostication, but model output as an independent prognostic factor must be validated with clinical risk factors. Purpose To develop and validate a preoperative CT-based deep learning model for predicting disease-free survival in patients with lung adenocarcinoma. Materials and Methods In this retrospective study, a deep learning model was trained to extract prognostic information from preoperative CT examinations. Data set 1 for training, tuning, and internal validation consisted of patients with T1-4N0M0 adenocarcinoma resected between 2009 and 2015. Data set 2 for external validation included patients with clinical T1-2aN0M0 (stage I) adenocarcinomas resected in 2014. Discrimination was assessed by using Harrell C index and benchmarked against the clinical T category. The Greenwood-Nam-D'Agostino test was used for model calibration. The multivariable-adjusted hazard ratios (HRs) were analyzed with clinical prognostic factors by using the Cox regression. Results Evaluated were 800 patients (median age, 64 years; interquartile range, 56-70 years; 450 women) in data set 1 and 108 patients (median age, 63 years; interquartile range, 57-71 years; 60 women) in data set 2. The C indexes were 0.74-0.80 in the internal validation and 0.71-0.78 in the external validation, both comparable with the clinical T category (0.78 in the internal validation and 0.74 in the external validation; all P > .05). The model exhibited good calibration in all data sets (P > .05). Multivariable Cox regression revealed that model outputs were independent prognostic factors (hazard ratio [HR] of the categorical output, 2.5 [95% confidence interval {CI}: 1.03, 5.9; P = .04] in the internal validation and 3.6 [95% CI: 1.6, 8.5; P = .003] in the external validation). Other than the deep learning model, only smoking status (HR, 3.4; 95% CI: 1.4, 8.5; P = .007) contributed further to prediction of disease-free survival for patients after resection of clinical stage I adenocarcinomas. Conclusion A deep learning model for chest CT predicted disease-free survival for patients undergoing an operation for clinical stage I lung adenocarcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Shaffer in this issue.

8.
Biofabrication ; 12(3): 035019, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32408287

RESUMO

High-throughput screening (HTS) is a well-established approach for tumor-specific drug development because of its high efficiency and customizable selection of antineoplastic drugs. However, there is still a lack of an appropriate cell-based HTS specific for migratory cancer cells. In the study presented here, we created a novel assay (mHTS): a single-cell-level screening method targeting migratory cancer cells and can be applied in a high-throughput manner. This mHTS platform is based on microchannel devices (providing physical confinement during cell migration and limit migrating cells' proliferation rate) assembled 96-well plate (fitting to HTS manner). To determine the feasibility of this assay, we quantified the anti-migratory and anti-viability effects of several molecules (Cytochalasin D, Doxorubicin and AZD-6244) on migrating (creeping inside microchannel) glioblastoma multiforme (GBM) cells. After analyzing migration screening data that was collected on a single-cell-level, we were able to compare those drug's effects on cancer cells' migration velocity and uncovered the migration inhibiting potential of AZD (500 nM and 1000 nM). Viability data based on single-cell-level screening also allowed us to further understand the same drug's different lethality toward migrating and normal 2D cultured cancer cells. The Pre-classification of subpopulations enables us to study the heterogeneity of cancer and ensures our method's feasibility for a high-throughput manner. All these results proved our mHTS platform is suitable for single-cell-level anti-migration drug screening and has potential feasibility in promoting the development of anti-migratory-cancer-drug in a high-throughput manner.

9.
Genes Genomics ; 42(7): 751-759, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32449066

RESUMO

BACKGROUND: The increase in genetic alterations targeted by specific chemotherapy in lung cancer has led to the need for universal use of more comprehensive genetic testing, which has highlighted the development of a lung cancer diagnostic panel using next-generation sequencing. OBJECTIVE: We developed a hybridization capture-based massively parallel sequencing assay named Friendly, Integrated, Research-based, Smart and Trustworthy (FIRST)-lung cancer panel (LCP), and evaluated its performance. METHODS: FIRST-LCP comprises 64 lung cancer-related genes to test for various kinds of genetic alterations including single nucleotide variations (SNVs), insertions and deletions (indels), copy number variations (CNVs), and structural variations. To assess the performance of FIRST-LCP, we compiled test sets using HapMap samples or tumor cell lines with disclosed genetic information, and also tested our clinical lung cancer samples whose genetic alterations were known by conventional methods. RESULTS: FIRST-LCP accomplished high sensitivity (99.4%) and specificity (100%) of the detection of SNVs. High precision was also achieved, with intra- or inter-run concordance rate of 0.99, respectively. FIRST-LCP detected indels and CNVs close to the expected allele frequency and magnitude, respectively. Tests with samples from lung cancer patients also identified all SNVs, indels and fusions. CONCLUSION: Based on the current state of the art, continuous application of the panel design and analysis pipeline following up-to-date knowledge could ensure precision medicine for lung cancer patients.

10.
J Thorac Oncol ; 15(7): 1119-1136, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32422364

RESUMO

The global coronavirus disease 2019 pandemic continues to escalate at a rapid pace inundating medical facilities and creating substantial challenges globally. The risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer seems to be higher, especially as they are more likely to present with an immunocompromised condition, either from cancer itself or from the treatments they receive. A major consideration in the delivery of cancer care during the pandemic is to balance the risk of patient exposure and infection with the need to provide effective cancer treatment. Many aspects of the SARS-CoV-2 infection currently remain poorly characterized and even less is known about the course of infection in the context of a patient with cancer. As SARS-CoV-2 is highly contagious, the risk of infection directly affects the cancer patient being treated, other cancer patients in close proximity, and health care providers. Infection at any level for patients or providers can cause considerable disruption to even the most effective treatment plans. Lung cancer patients, especially those with reduced lung function and cardiopulmonary comorbidities are more likely to have increased risk and mortality from coronavirus disease 2019 as one of its common manifestations is as an acute respiratory illness. The purpose of this manuscript is to present a practical multidisciplinary and international overview to assist in treatment for lung cancer patients during this pandemic, with the caveat that evidence is lacking in many areas. It is expected that firmer recommendations can be developed as more evidence becomes available.


Assuntos
Infecções por Coronavirus , Controle de Infecções/organização & administração , Neoplasias Pulmonares/terapia , Pandemias , Administração dos Cuidados ao Paciente , Pneumonia Viral , Betacoronavirus/isolamento & purificação , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Comunicação Interdisciplinar , Cooperação Internacional , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Pandemias/prevenção & controle , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Administração dos Cuidados ao Paciente/tendências , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Prognóstico
11.
Psychooncology ; 29(7): 1105-1114, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32307828

RESUMO

OBJECTIVES: To investigate the efficacy of health coaching and a web-based program on survivor physical activity (PA), weight, and distress management among stomach, colon, lung and breast cancer patients. METHODS: This randomised, controlled, 1-year trial conducted in five hospitals recruited cancer survivors within 2 months of completing primary cancer treatment who had not met ≥1 of these behavioural goals: (i) conducting moderate PA for at least 150 minutes/week or strenuous exercise for over 75 minutes per week or, in the case of lung cancer patients, low or moderate intensity exercise for over 12.5 MET per week, (ii) maintaining normal weight, and (iii) attaining a score >72 in the Post Traumatic Growth Inventory (PTGI). Participants were randomly assigned to one of three groups: the control group, a web-only group, or a health coaching + web group. The primary endpoint was based on a composite of PA, weight, and PTGI score at 12 months. RESULTS: Patients in the health coaching + web group (difference = 6.6%, P = .010) and the web-only group (difference = 5.9%, P = .031) had greater overall improvements across the three-outcome composite than the control group. The health coaching + web group had greater overall improvement in PTGI (difference = 12.6%; P < .001) than the control group, but not in PA and weight. CONCLUSION: The web-based program, with or without health coaching, may improve health behaviours including PA, weight, and distress management among cancer survivors within 2 months of completing primary cancer treatment. The web-based program with health coaching was mainly effective for reducing psychological distress.

12.
Yonsei Med J ; 61(4): 284-290, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32233170

RESUMO

PURPOSE: We evaluated whether adding bevacizumab to current platinum-based chemotherapy could improve clinical outcomes without affecting safety. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with pathologically confirmed ovarian cancer who received neoadjuvant chemotherapy (NAC) at Yonsei Cancer Hospital. We divided the patients into groups based on the use of bevacizumab for NAC (CP group: carboplatin+paclitaxel vs. BCP group: bevacizumab+carboplatin+paclitaxel) and compared patient characteristics, responses to NAC, and surgical and survival outcomes between the two groups. Overall, 88 patients in the CP group and 16 patients in the BCP group received NAC. The primary endpoint was survival outcomes. Complete resection rate after interval debulking surgery (IDS), cancer antigen 125 (CA-125) normalization after NAC, and chemotherapy response score were secondary endpoints. RESULTS: After NAC treatment, all patients underwent IDS. There were no significant differences in adverse events during NAC or postoperative complications between the two groups (p=0.293 and p=0.485, respectively). There were also no significant differences in CA-125 normalization after NAC (42.0% vs. 43.8%, p=0.899) or complete resection rate after IDS (47.7% vs. 56.3%, p=0.530). However, although the BCP group did not show longer overall survival (OS) (log-rank p=0.854), they had significantly longer progression-free survival (PFS) than the CP group (log-rank p=0.048). CONCLUSION: Bevacizumab-containing NAC might be safe and provide longer PFS than chemotherapy alone in patients with advanced ovarian cancer. However, further study is necessary to investigate the impact of bevacizumab-containing NAC on OS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Epitelial do Ovário/terapia , Terapia Neoadjuvante , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Antígeno Ca-125 , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos de Citorredução/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Complicações Pós-Operatórias , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
BMC Cancer ; 20(1): 185, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32131779

RESUMO

BACKGROUND: To analyze the effects of BRCA1/2 mutations on chemotherapy response scores (CRS) and survival in a cohort of patients with advanced-stage ovarian cancer who were treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS). METHODS: We retrospectively reviewed the medical records of 169 high-grade serous ovarian cancer patients who underwent a germline BRCA1/2 test and received three cycles of NAC at the Yonsei Cancer Center from 2006 to 2018. Chemotherapy response scores were compared in patients with and without BRCA1/2 mutations. The effects of BRCA1/2 mutations and CRS on survival were evaluated. RESULTS: BRCA1/2 mutations were detected in 47 (28.1%) of the 169 patients. Overall, 16 (34.0%) patients with BRCA1/2 mutations had a CRS 3 to chemotherapy compared to scores of 43 in patients (35.2%) without a mutation. Response scores of 3 in patients with BRCA1/2 mutations were not significantly associated with either improved progression-free survival (PFS) (P = 0.949) or overall survival (OS) (P = 0.168). However, CRS 3 in patients without BRCA mutations was significantly associated with both improved PFS (P = 0.030) and OS (P = 0.039). In patients with CRS1/2, carriers of BRCA1/2 mutations had better PFS (P = 0.0344) and OS (P = 0.043) than wild-type BRCA genotype patients. CONCLUSION: In ovarian cancer patients treated with NAC, CRS did not predict survival for BRCA 1/2 mutation carriers but did for BRCA wild-type patients.

14.
BMC Cancer ; 20(1): 204, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164585

RESUMO

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors targeting BRCA1/2 mutations are available for treating patients with high-grade serous ovarian cancer. These treatments may be more appropriately directed to patients who might respond if the tumor tissue is additionally tested by next-generation sequencing with a multi-gene panel and Sanger sequencing of a blood sample. In this study, we compared the results obtained using the next-generation sequencing multi-gene panel to a known germline BRCA1/2 mutational state determined by conventional Sanger sequencing to evaluate the landscape of somatic mutations in high-grade serous ovarian cancer tumors. METHODS: Cancer tissue from 98 patients with high-grade serous ovarian cancer who underwent Sanger sequencing for germline BRCA1/2 analysis were consecutively analyzed for somatic mutations using a next-generation sequencing 170-gene panel. RESULTS: Twenty-four patients (24.5%) showed overall BRCA1/2 mutations. Seven patients (7.1%) contained only somatic BRCA1/2 mutations with wild-type germline BRCA1/2, indicating acquired mutation of BRCA1/2. Three patients (3.1%) showed reversion of germline BRCA1 mutations. Among the 14 patients (14.3%) with both germline and somatic mutations in BRCA1/2, two patients showed different variations of BRCA1/2 mutations. The next-generation sequencing panel test for somatic mutation detected other pathogenic variations including RAD51D and ARID1A, which are possible targets of poly (ADP-ribose) polymerase inhibitors. Compared to conventional Sanger sequencing alone, next-generation sequencing-based tissue analysis increased the number of candidates for poly (ADP-ribose) polymerase inhibitor treatment from 17.3% (17/98) to 26.5% (26/98). CONCLUSIONS: Somatic mutation analysis by next-generation sequencing, in addition to germline BRCA1/2 mutation analysis, should become the standard of care for managing women with high-grade serous ovarian cancer to widen the indication of poly (ADP-ribose) polymerase inhibitors.

15.
Medicine (Baltimore) ; 99(11): e19533, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176106

RESUMO

We investigated the prognosis of patients with dry pleural dissemination (DPD) of non-small cell lung cancer (NSCLC) and the risk factors of developing to malignant pleural effusion (MPE).We retrospectively reviewed 104 patients with NSCLC and DPD, confirmed surgically from 1996 to 2016. Incidence rate and risk factors of MPE were analyzed statistically. The prognosis of NSCLC patients with MPE was evaluated using the Kaplan-Meier method.The most common histologic type was adenocarcinoma in 95 (91.3%) patients. The median follow-up duration was 65.5 months and the median survival time was 37.7 months. MPE developed in 51 (49%) patients, and the median effusion-free interval was 41.9 months. The median survival time of the patients with and without MPE was not different (41.3 vs 31.7 months, P = .16). No predictive factors for the development of MPE were identified. Fifteen (14.4%) patients underwent invasive procedures for the management of MPE.Almost half of all patients with NSCLC and DPD experienced MPE, and 14.4% patients developed symptomatic MPE requiring invasive procedures. MPE in DPD did not affect the survival in NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Derrame Pleural Maligno/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/mortalidade , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida
16.
Artigo em Inglês | MEDLINE | ID: mdl-32061085

RESUMO

OBJECTIVES: Robotic thymectomy via the subxiphoid approach (RTX) is a recently introduced surgical approach. This study aimed to report on the surgical technique and early outcomes of RTX in our institute. METHODS: RTX was performed using the 3-arm technique in the da Vinci robotic surgical system. The camera was inserted into a subxiphoid port, and 2 robotic arms were inserted in bilateral intercostal ports. A complete dissection of both cervical poles up to the thyroid gland was conducted, and bilateral phrenic nerves were identified in all cases. Radical combined resection of adjacent organs, including the lung, pericardium, phrenic nerve and the innominate vein, was performed if necessary. The resected specimen could be retrieved through the subxiphoid port site. RESULTS: A total of 110 patients underwent RTX in our institute from October 2016 to August 2019. Thymoma was the most common diagnosis (60.9%), and the mean size of the tumours was 4.9 ± 2.4 cm. Combined resection was performed in the lung (n = 9, 8.1%), pericardium (n = 6, 5.5%) and innominate vein (n = 5, 4.5%). There were 2 minor postoperative complications (1.8%), and the mean length of hospital stay was 2.2 ± 1.4 days. For the cumulative sum curve analysis of the learning curve using operative time, 50 cases were necessary to gain proficiency. CONCLUSIONS: RTX was a safe and feasible surgical approach, even in advanced thymic epithelial tumours. It should be considered one of the valuable surgical options in minimally invasive thymectomy.

17.
BMC Cancer ; 20(1): 152, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093687

RESUMO

BACKGROUND: Despite recent advances in diagnosis and treatment, cervical cancer continues to be a significant health problem worldwide. Whereas robot-assisted surgery has advantages over the abdominal approach, and minimally invasive techniques are being used increasingly, these may be associated with a higher recurrence rate and lower overall survival than the abdominal approach. The objective of this study was to compare the surgical and survival outcomes between abdominal radical hysterectomy (ARH) and robotic radical hysterectomy (RRH). METHODS: A retrospective cohort of patients undergoing radical hysterectomy for cervical cancer from 2006 to 2018 was identified. Patients with stage IA to IB cervical cancer were included and grouped: ARH vs. RRH. The RRH group was further divided into two groups based on the year of enrollment: RRH1 (2006-2012) and RRH2 (2013-2018). Tumor characteristics, recurrence rate, progression-free survival (PFS), and overall survival (OS) were compared between the groups. P-values < 0.05 (two-sided) were considered statistically significant. RESULTS: A total of 310 patients were identified: 142 and 168 underwent ARH and RRH, respectively. RRH1 and RRH2 had 77 and 91 patients, respectively. Interestingly, RRH2 was more likely to have a larger tumor size (1.7 ± 1.4 vs. 2.0 ± 1.1 vs. 2.4 ± 1.7 cm, P = 0.014) and higher stage (P < 0.001) than RRH1. However, RRH2 showed significantly favorable PFS in contrast to RRH1. There was no difference between ARH and RRH2 in PFS (P = 0.629), whereas overall, the RRH group showed significantly shorter PFS than the ARH group. In the multivariate analysis, the institutional learning curve represented by the operation year was one of the significant predictors for PFS (hazard ratio [HR] 0.065, P = 0.0162), along with tumor size (HR 5.651, P = 0.0241). CONCLUSIONS: The institutional learning curve, represented by the operation year, is one of the most significant factors associated with outcomes of RRH for early-stage cervical cancer.

18.
Int J Gynecol Cancer ; 30(3): 318-324, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31992601

RESUMO

INTRODUCTION: Fluorescence image-guided sentinel lymph node (SLN) biopsy using a two-step mapping technique incorporates sequential injection of indocyanine green into the bilateral uterine cornus, followed by cervical injection. Outcomes were compared with the conventional cervical (one-step) method . METHODS: Patients with FIGO stage I-III endometrial cancer who underwent laparoscopic or robotic staging, including SLN biopsy, from May 2014 to December 2018, were retrospectively reviewed. Patient characteristics, pre-operative imaging, SLN detection pattern, pathologic result, adjuvant, and recurrence locations were analyzed. RESULTS: A total of 199 patients received one-step (n=123) and two-step (n=76) SLN biopsy. Para-aortic SLN were more frequently identified in the two-step group. Lower and upper para-aortic SLN were identified in 67.1% and 38.2%, respectively, in the two-step group and in 18.7% and 5.7% in the one-step group (p<0.001). The number of para-aortic SLN harvested was superior in the two-step group (p<0.001). Metastatic para-aortic SLN were found in 7.9% of the two-step group and 2.4% of the one-step group (p=0.070). In detecting nodal metastasis, the sensitivities of the one- and two-step methods were 91.7% and 100.0%, negative predictive values were 99.0% and 100.0%, false-negative rates were 8.3% and 0%, and accuracy rates were 99.1% and 100.0%, respectively. The one-step method identified only three out of eight para-aortic lymph node metastases and missed five para-aortic lymph node metastases. There was no missed para-aortic lymph node metastasis in the two-step group. Recurrence was observed in two patients (2.6%; vaginal vault and adrenal gland) in the two-step group and seven patients (5.7%) including three nodal recurrences in the one-step group (p=0.307). DISCUSSION: Two-step SLN mapping improved the para-aortic SLN detection rate, a known pitfall of conventional cervical injection. Proper evaluation of aortic nodal status will assist in the tailoring of adjuvant and prevent undertreatment of patients with isolated para-aortic metastasis.

19.
Respir Res ; 21(1): 20, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931798

RESUMO

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation has greatly increased. However, data regarding the clinical outcomes of this approach are lacking. The objective of this multicenter prospective observational cohort study was to evaluate lung transplantation outcomes in Korean Organ Transplantation Registry (KOTRY) patients for whom ECMO was used as a bridge to transplantation. METHODS: Between March 2015 and December 2017, a total of 112 patients received lung transplantation and were registered in the KOTRY, which is a prospective, multicenter cohort registry. The entire cohort was divided into two groups: the control group (n = 85, 75.9%) and bridge-ECMO group (n = 27, 24.1%). RESULTS: There were no significant differences in pre-transplant and intraoperative characteristics except for poorer oxygenation, more ventilator use, and longer operation time in the bridge-ECMO group. The prevalence of primary graft dysfunction at 0, 24, 48, and 72 h after transplantation did not differ between the two groups. Although postoperative hospital stays were longer in the bridge-ECMO group than in the control group, hospital mortality did not differ between the two groups (25.9% vs. 13.3%, P = 0.212). The majority of patients (70.4% of the bridge-ECMO group and 77.6% of the control group) were discharged directly to their homes. Finally, the use of ECMO as a bridge to lung transplantation did not significantly affect overall survival and graft function. CONCLUSIONS: Short- and long-term post-transplant outcomes of bridge-ECMO patients were comparable to recipients who did not receive ECMO.

20.
Int J Biol Sci ; 16(2): 320-329, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929759

RESUMO

The transcription factor E2F is an important modulator of the cell cycle, and the unrestricted activation of E2F-dependent transcription is considered to be an important driver of tumor formation and progression. E2F8 is known to play an important role in embryonic development and cell cycle control by inhibiting E2F1. However, it is not yet known whether E2F8 is involved in the progression of cervical cancer. In this study, the functional consequences of E2F8 knockdown in vitro and in vivo were explored. To demonstrate the function of E2F8 in cell proliferation, migration and invasion, we knocked down E2F8 in cervical cancer cell lines; in vitro and in vivo experiments using this knockdown showed that E2F8 potently induced the expression of epithelial-mesenchymal transition (EMT) markers. Finally, clinical data confirmed that E2F8 was a significant predictive factor for progression-free survival, and that patients with cervical cancer who exhibited high expression of E2F8 showed high FIGO stages and frequent recurrence rates compared to patients with low E2F8 expression. In conclusion, our study suggests that E2F8 is highly correlated with the progression-free survival of cervical cancer patients.

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