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1.
Anticancer Res ; 39(10): 5631-5637, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570460

RESUMO

BACKGROUND/AIM: Pelvic exenteration is a radical procedure for certain advanced or recurrent gynaecological cancers, performed with curative or palliative intent. Its validity has evolved as operative mortality and morbidity have improved. This surgery was evaluated to determine the validity of these claims. PATIENTS AND METHODS: The details of surgery and outcomes of 13 patients who underwent pelvic exenteration (6 curative intent, 7 palliative intent) for advanced or recurrent gynaecological cancers in our Department were retrospectively evaluated. RESULTS: There were no significant differences in blood loss, surgical time, hospital stay, and complications between curative pelvic exenteration and palliative pelvic exenteration. The curative intent group had a good prognosis; the palliative-intent group showed a trend to a worse prognosis. All patients' symptoms were relieved, but in patients with short survival, symptom relief lasted for up to 3 months. CONCLUSION: Pelvic exenteration is an acceptable and valuable procedure for gynaecological cancers.


Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Feminino , Neoplasias dos Genitais Femininos/mortalidade , Ginecologia/métodos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Duração da Cirurgia , Exenteração Pélvica/métodos , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Adulto Jovem
2.
Bone Joint J ; 101-B(10): 1313-1320, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31564158

RESUMO

AIMS: The aim of this study was to report the outcomes of patients who underwent definitive surgery for secondary chondrosarcomas arising from osteochondromas. PATIENTS AND METHODS: A total of 51 patients with secondary chondrosarcomas occurring from osteochondromas were reviewed. Median age was 36 years (interquartile range (IQR) 15 to 82). Median follow-up was 6.9 years (IQR 2.8 to 10.6). The pelvis was the most commonly affected site (59%). Histological grades were grade I in 35 (69%), grade II in 13 (25%), and grade III in three patients (6%). RESULTS: Preoperative biopsy histology correctly predicted the final histological grade in 27% of patients. The ten-year disease-specific survival (DSS) for all patients was 89.4%. Local recurrence occurred in 15 patients (29%), more commonly in pelvic tumours (37%) compared with limb tumours (19%). Four patients with pelvic tumours died from progression of local recurrence. No patient with limb tumours died of disease. Wide/radical margin was associated with improved local recurrence-free survival (p = 0.032) and local recurrence was associated with worse DSS (p = 0.005). CONCLUSION: We recommend that a secondary chondrosarcoma arising from osteochondroma of the pelvis is resected with wide/radical resection margins. The balance between the morbidity of surgery and risk of local recurrence needs to be considered in patients with limb secondary chondrosarcomas. Cite this article: Bone Joint J 2019;101-B:1313-1320.


Assuntos
Neoplasias Ósseas/patologia , Condrossarcoma/secundário , Recidiva Local de Neoplasia/mortalidade , Osteocondroma/patologia , Adulto , Biópsia por Agulha , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/cirurgia , Condrossarcoma/diagnóstico por imagem , Condrossarcoma/mortalidade , Condrossarcoma/cirurgia , Estudos de Coortes , Intervalo Livre de Doença , Extremidades/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Osteocondroma/diagnóstico por imagem , Osteocondroma/mortalidade , Osteocondroma/cirurgia , Ossos Pélvicos/patologia , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
3.
Anticancer Res ; 39(10): 5747-5753, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570477

RESUMO

BACKGROUND/AIM: Liposarcomas (LS) are one of the most common entities within the heterogenous group of soft tissue sarcomas. The aim of this study was to identify prognostic indicators in patients with LS of the extremities and truncal wall. PATIENTS AND METHODS: We analysed the influence of potential prognostic factors on local recurrence-free survival (LRFS) and overall survival (OS) in 181 patients who were suitable for surgical treatment with curative intent. RESULTS: The median follow-up period was 7.1 years. The 5-year LRFS and OS rates were 79.1 and 93.3%. The 5-year OS rate was 94.7% in patients with R0-resected primary tumors and 72.7% in patients with R1/R2-status (p=0.023). In multivariate analysis, only histologic grade was found to be an independent prognostic factor of OS. CONCLUSION: Negative margins were not an independent prognostic factor in our series. Tumor biology reflected by histologic grade dictated the outcome.


Assuntos
Extremidades/patologia , Lipossarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lipossarcoma/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Adulto Jovem
4.
Medicine (Baltimore) ; 98(33): e16855, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415417

RESUMO

BACKGROUND: Endometrial cancer (EC) is one of the most common gynecologic tumors, with a high incidence in developed countries. Although the overall prognosis is good, some women have invasive tumors, the risk of recurrence, and death is high. The common surgical methods used in EC are total-abdominal hysterectomy (TAH), total-vaginal hysterectomy (TVH), laparoscopic-assisted vaginal hysterectomy (LAVH), and total-laparoscopic hysterectomy (TLH) including both conventional and robotically assisted. METHODS: The literature search was performed in The Cochrane Central Register of Controlled Trials, PubMed, Web of Science, and Embase. The randomized controlled trials (RCTs) will be included. The search date is until June 2019. The risk of bias of included RCTs was assessed by 2 investigators according to the Cochrane Collaboration's tool. Network meta-analysis will be conducted by R software. RESULTS: This study is ongoing and the results will be submitted to a peer-reviewed journal for publication. CONCLUSION: This network meta-analysis will provide clinical staff with current and reliable information on the best surgical approach for EC. Ethical approval is not applicable, since this is a network mate-analysis based on published articles. The protocol has been registered on PROSPERO under the number CRD42019128094.


Assuntos
Neoplasias do Endométrio/cirurgia , Histerectomia Vaginal/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Laparoscopia/métodos , Recidiva Local de Neoplasia/mortalidade , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/métodos
5.
Bone Joint J ; 101-B(8): 1024-1031, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31362545

RESUMO

AIMS: The aim of this study was to determine the risk of local recurrence and survival in patients with osteosarcoma based on the proximity of the tumour to the major vessels. PATIENTS AND METHODS: A total of 226 patients with high-grade non-metastatic osteosarcoma in the limbs were investigated. Median age at diagnosis was 15 years (4 to 67) with the ratio of male to female patients being 1.5:1. The most common site of the tumour was the femur (n = 103) followed by tibia (n = 66). The vascular proximity was categorized based on the preoperative MRI after neoadjuvant chemotherapy into four types: type 1 > 5 mm; type 2 ≤ 5 mm, > 0 mm; type 3 attached; type 4 surrounded. RESULTS: Limb salvage rate based on the proximity type was 92%, 88%, 51%, and 0% for types 1 to 4, respectively, and the overall survival at five years was 82%, 77%, 57%, and 67%, respectively (p < 0.001). Local recurrence rate in patients with limb-salvage surgery was 7%, 8%, and 22% for the types 1 to 3, respectively (p = 0.041), and local recurrence at the perivascular area was observed in 1% and 4% for type 2 and 3, respectively. The mean microscopic margin to the major vessels was 6.9 mm, 3.0 mm, and 1.4 mm for types 1 to 3, respectively. In type 3, local recurrence-free survival with limb salvage was significantly poorer compared with amputation (p = 0.025), while the latter offered no overall survival benefit. In this group of patients, factors such as good response to chemotherapy or limited vascular attachment to less than half circumference or longitudinal 10 mm reduced the risk of local recurrence. CONCLUSION: The proximity of osteosarcoma to major blood vessels is a poor prognostic factor for local control and survival. Amputation offers better local control for tumours attached to the blood vessels but does not improve survival. Limb salvage surgery offers similar local control if the tumour attachment to blood vessels is limited. Cite this article: Bone Joint J 2019;101-B:1024-1031.


Assuntos
Vasos Sanguíneos/diagnóstico por imagem , Neoplasias Femorais/cirurgia , Imagem por Ressonância Magnética , Recidiva Local de Neoplasia/etiologia , Osteossarcoma/cirurgia , Cuidados Pré-Operatórios/métodos , Tíbia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Neoplasias Femorais/diagnóstico por imagem , Neoplasias Femorais/mortalidade , Neoplasias Femorais/patologia , Seguimentos , Humanos , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/mortalidade , Osteossarcoma/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Tíbia/diagnóstico por imagem , Tíbia/patologia , Tíbia/cirurgia , Adulto Jovem
6.
J Surg Oncol ; 120(4): 746-752, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286523

RESUMO

BACKGROUND AND OBJECTIVES: Local recurrence in Ewing sarcoma (ES) is associated with poor prognosis. The purpose of the study is to determine what factors affect overall survival after local recurrence and whether wide excision constitutes appropriate treatment. METHODS: From 1992 to 2017, 26 patients were treated for local recurrence of ES. Sixteen patients presented with local recurrence only while 10 had metastasis. The median follow-up was 23 months (range, 3-255 months). Overall survival was assessed with Kaplan-Meier analysis. RESULTS: At the last follow-up, seven of 26 (27%) patients were alive. Overall survival after local recurrence was 28% at 5 years. Later onset of local recurrence (P = .041), surgical treatment (P < .001), and complete eradication of all recurrent disease (P < .001) predicted better survival. Metastasis was associated with worse survival (P = .014). All three patients who survived more than 10 years were treated with wide local excision. A second local recurrence developed in seven patients (28%) but did not predict worse overall survival. CONCLUSIONS: Overall survival after local recurrence is better for patients with nonmetastatic disease treated surgically. Wide excision can be compatible with long survival. We do not advocate amputation on a routine basis for local recurrence. Complete eradication of all diseases is associated with better survival.


Assuntos
Neoplasias Ósseas/mortalidade , Recidiva Local de Neoplasia/mortalidade , Sarcoma de Ewing/mortalidade , Procedimentos Cirúrgicos Operatórios/mortalidade , Adolescente , Adulto , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Sarcoma de Ewing/patologia , Sarcoma de Ewing/cirurgia , Taxa de Sobrevida , Adulto Jovem
7.
J Surg Oncol ; 120(4): 729-735, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290159

RESUMO

BACKGROUND AND OBJECTIVES: While knowledge has grown extensively regarding the impact of mutations on colorectal cancer prognosis, their role in outcomes after pulmonary metastasectomy (PM) remains minimally understood. We sought to determine the prognostic role of mutant disease on survival and recurrence after metastasectomy. METHODS: Patients with available tumor sequencing profiles who underwent PM for colorectal cancer at a single institution from 2011 to 2017 were reviewed. Various demographic and clinicopathologic factors, as well as mutational status, were tested in the Cox regression analyses to identify predictors of survival and disease-free survival (DFS). RESULTS: A total of 130 patients met inclusion criteria, among whom 78 (60%) were male and the mean age was 57 years. The median survival time and 5-year survival rate were 58.2 months and 47%, respectively. A single pulmonary nodule was present in 54%. Disease recurrence occurred for 87 (67%) patients, including 75 (58%) who had at least one lung recurrence after metastasectomy at a median time to recurrence of 19.4 months. Upon multivariable analysis, RAS and TP53 mutations were associated with shorter survival DFS, while APC is associated with prolonged survival. CONCLUSIONS: After metastasectomy for colorectal cancer, mutations in RAS, TP53, and APC play an important role in survival and recurrence.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Pulmonares/mortalidade , Metastasectomia/mortalidade , Mutação , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia/mortalidade , Adulto , Idoso , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
8.
J Surg Oncol ; 120(4): 768-778, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31297837

RESUMO

BACKGROUND AND OBJECTIVES: Lymphadenectomy during pulmonary metastasectomy (PM) is widely carried out. We assessed the potential benefit on patient survival and tumor recurrence of this practice. METHODS: One hundred eighty-one patients undergoing a first PM were studied. Eighty-six patients (47.5%) underwent lymphadenectomy (L+ group) whereas 95 (52.5%) did not undergo nodal harvesting (L-group). Main outcomes were overall survival (OS) and disease-free survival (DFS). Median follow-up was 25 months (interquartile range [IQR], 13-49). RESULTS: At follow-up 84 patients (46.4%) died, whereas 97 (53.6%) were still alive with recurrence in 78 patients (43%). There was no difference in 5-year survival (L+ 30.0% vs L- 43.2%; P = .87) or in the 5-year cumulative incidence of recurrence (L + 63.2% vs L-80%; P = .07) between the two groups. Multivariable analysis indicated that disease-free interval (DFI) less than 29 months (P < .001) and lung comorbidities (P = .003) were significant predictors of death. Metastases from non-small-cell lung cancer increased the risk of lung comorbidities by a factor of 19.8, whereas the risk of DFI less than 29 months was increased nearly 11-fold. Competing risk regression identified multiple metastases (P = .004), head/neck primary tumor (P = .009), and age less than 67 years (P = .024) as independent risk factors for recurrence. CONCLUSION: Associated lymphadenectomy showed not to give any additional advantage in terms of survival and recurrence after PM.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/mortalidade , Excisão de Linfonodo/mortalidade , Metastasectomia/mortalidade , Recidiva Local de Neoplasia/mortalidade , Pneumonectomia/mortalidade , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Fatores de Risco , Taxa de Sobrevida
9.
J Surg Oncol ; 120(4): 632-638, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31339198

RESUMO

BACKGROUND: Preoperative systemic inflammatory response plays a crucial role in tumorigenesis, progression, and prognosis; and neutrophil, monocyte, and lymphocyte counts serve as important biomarkers. An altered monocyte-to-lymphocyte ratio (MLR) and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with a favorable prognosis for certain hematologic malignancies and breast cancer. The aim of this study was to investigate the prognostic significance of MLR, NLR in patients with resectable PNETs. METHODS: Patients undergoing surgery for PNETs between 2000 and 2016 were identified using a large, multi-center database. NLR and MLR were calculated and Contal and O'Quigley analysis was used to determine the optimal cutoff value. RESULTS: A total of 620 patients were included in the analytic cohort. The prognostic implications of blood count parameters were evaluated in both univariate and multivariate analysis. The univariate analysis revealed that low MLR and NLR is associated with significantly improved overall survival (OS; P < .01) and recurrence-free survival (RFS; P < .01). On multivariate analysis, in addition to tumor size and grade, NLR was an independent predictor of improved OS and RFS. CONCLUSION: In addition to established tumor-specific factors, preoperative NLR levels can serve as a valuable biomarker that can be used as a predictor of OS and RFS after resection of PNETs.


Assuntos
Linfócitos/patologia , Monócitos/patologia , Recidiva Local de Neoplasia/mortalidade , Tumores Neuroendócrinos/mortalidade , Neutrófilos/patologia , Pancreatectomia/mortalidade , Neoplasias Pancreáticas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Cancer Sci ; 110(9): 2924-2932, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31336012

RESUMO

This multicenter, open-label phase 1/2 study evaluated single-agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2 . Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3-39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3-37.5) with 2.5% (n = 1) stringent complete response. Median progression-free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8-13.6) and 22.9 months (95% CI, 14.1-not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long-term carfilzomib monotherapy led to long-term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients.


Assuntos
Antineoplásicos/administração & dosagem , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Oligopeptídeos/administração & dosagem , Idoso , Antineoplásicos/efeitos adversos , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Leucopenia/induzido quimicamente , Leucopenia/epidemiologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Neutropenia/induzido quimicamente , Neutropenia/epidemiologia , Oligopeptídeos/efeitos adversos , Intervalo Livre de Progressão , Análise de Sobrevida
11.
Cancer Sci ; 110(9): 2894-2904, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348579

RESUMO

Nivolumab is a human monoclonal antibody against the immune checkpoint receptor programmed death-1, inhibiting binding to programmed death-ligand 1 or 2 (PD-L1 or PD-L2). This phase 2 study evaluated the efficacy and safety of nivolumab in patients with advanced/recurrent uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma (STS). Patients received nivolumab 240 mg at 2-week intervals. Primary endpoint was objective response rate; secondary endpoints included overall survival, progression-free survival, and safety. PD-L1 expression and microsatellite-instability (MSI) status were analyzed as potential efficacy biomarkers. Objective response rate was 25%, 23%, and 0% in patients with cervical cancer (n = 20), corpus cancer (n = 22), and STS (n = 21), respectively. The lower 80% confidence intervals of objective response rates in patients with cervical or corpus cancer exceeded the threshold rate (5%); the primary endpoint was met in cervical and corpus cancer, but not in STS. Median progression-free survival was 5.6, 3.4, and 1.4 months, and 6-month overall survival was 84%, 73%, and 86% in cervical cancer, corpus cancer, and STS, respectively. The objective response rate was higher in patients with cervical cancer with PD-L1-positive (n = 5/15; 33%) versus PD-L1-negative (n = 0/5; 0%) tumors. The two patients with corpus cancer classified as MSI-high responded; the six patients classified as microsatellite stable did not respond. Overall, nivolumab showed acceptable toxicity in all cohorts, with evidence of clinical activity in uterine cervical or corpus cancer, but not in STS. PD-L1 expression in cervical cancer and MSI-high in corpus cancer may predict clinical activity of nivolumab in these cancers.


Assuntos
Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Nivolumabe/administração & dosagem , Sarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Antígeno B7-H1/metabolismo , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Japão/epidemiologia , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Intervalo Livre de Progressão , Estudos Prospectivos , Sarcoma/genética , Sarcoma/mortalidade , Sarcoma/patologia , Análise de Sobrevida , Neoplasias Uterinas/genética , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Útero/patologia
12.
Anticancer Res ; 39(6): 3033-3038, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31177145

RESUMO

BACKGROUND/AIM: Treatment algorithms for primary and recurrent hepatocellular carcinoma (HCC) are described in the current Japanese Clinical Practice Guidelines; however, primary and recurrent tumors exhibit several differences in oncological characteristics such as clinicopathological features and prognostic factors. This study aimed to investigate the prognostic factors for recurrent HCC including time of recurrence after primary hepatectomy, to elucidate appropriate treatment strategies in these patients. PATIENTS AND METHODS: One hundred and nine patients who had undergone radical resection of primary HCC at our Hospital and had experienced intrahepatic recurrence were included in this study. Patients were categorized into the early-recurrence (ER, <1 year postoperatively) or the late-recurrence (LR, ≥1 year postoperatively) groups. Clinicopathological features were compared between the two groups for prognostic analyses. RESULTS: Comparison of clinicopathological features between the ER and LR groups revealed that, at the time of recurrence, the ER group had a significantly higher frequency of multiple recurrences compared to the LR group. In univariate prognostic analysis, the time of recurrence (ER or LR) and the number of recurrent tumors (≥3) were significant prognostic factors after recurrence. Multivariate analysis revealed that three or more recurrent tumors and ER were independent prognostic factors for poor survival after recurrence. CONCLUSION: HCC is likely to recur, and the characteristics of recurrent HCC are distinct from those of primary HCC. To improve post-recurrence poor prognosis, new and more feasible algorithms, such as aggressive surgical treatment for cases with less than three recurrent tumors, which were revealed in the current study, are needed.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/terapia , Idoso , Algoritmos , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Am Surg ; 85(4): 384-389, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043199

RESUMO

The purpose of this study was to evaluate the clinicopathological features and prognosis of patients who underwent surgery for remnant gastric cancer (RGC) during/after the regular five-year follow-up period after initial distal gastrectomy for gastric cancer that is recommended by the Japanese gastric cancer treatment guidelines. Between January 2007 and December 2017, 40 patients underwent surgery for RGC after distal gastrectomy. Twenty-eight of the 40 patients underwent initial gastrectomy for cancer. We divided the 28 patients into two groups: patients who were diagnosed with RGC during/after the five-year follow-up period after initial gastrectomy, and analyzed their retrospectively collected data. Among the 28 patients, 15 patients were diagnosed with RGC within five years and 13 patients were diagnosed with RGC after five years. There were significant differences in the reconstruction of the initial operation, curative resection, pathological depth of the tumor, and pathological stage of the two groups. Multivariate analyses revealed that the interval between initial gastrectomy and RGC and the pathological TNM stage were significant risk factors for shorter cancer-specific survival. Kaplan-Meier analyses demonstrated that patients with RGC after the five-year follow-up period had a significantly worse prognosis in terms of cancer-specific survival than those who developed RGC within five years. This study suggested surveillance by using the annual endoscopy might be necessary beyond the initial five-year period for patients who underwent gastrectomy for gastric cancer.


Assuntos
Gastrectomia , Coto Gástrico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Gástricas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Análise de Sobrevida
14.
Nat Commun ; 10(1): 2115, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073170

RESUMO

Approximately 30% of ERα breast cancer patients relapse with metastatic disease following adjuvant endocrine therapies. The connection between acquisition of drug resistance and invasive potential is poorly understood. In this study, we demonstrate that the type II keratin topological associating domain undergoes epigenetic reprogramming in aromatase inhibitors (AI)-resistant cells, leading to Keratin-80 (KRT80) upregulation. KRT80 expression is driven by de novo enhancer activation by sterol regulatory element-binding protein 1 (SREBP1). KRT80 upregulation directly promotes cytoskeletal rearrangements at the leading edge, increased focal adhesion and cellular stiffening, collectively promoting cancer cell invasion. Shearwave elasticity imaging performed on prospectively recruited patients confirms KRT80 levels correlate with stiffer tumors. Immunohistochemistry showed increased KRT80-positive cells at relapse and, using several clinical endpoints, KRT80 expression associates with poor survival. Collectively, our data uncover an unpredicted and potentially targetable direct link between epigenetic and cytoskeletal reprogramming promoting cell invasion in response to chronic AI treatment.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/patologia , Citoesqueleto/patologia , Queratinas Tipo II/genética , Recidiva Local de Neoplasia/patologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Citoesqueleto/genética , Resistencia a Medicamentos Antineoplásicos/genética , Elementos Facilitadores Genéticos/genética , Epigênese Genética , Receptor alfa de Estrogênio/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Queratinas Tipo II/metabolismo , Células MCF-7 , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Domínios Proteicos/genética , Regulação para Cima
15.
BMC Cancer ; 19(1): 421, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060539

RESUMO

BACKGROUND: Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR. METHODS: Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-ß, and PI3K). RESULTS: Mutation of genes within the WNT, P53, RTK-RAS, TGF-ß, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-ß pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-ß pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-ß pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-ß pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation. CONCLUSIONS: Mutation in genes within TGF-ß pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.


Assuntos
Adenocarcinoma Mucinoso/genética , Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Transdução de Sinais/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Quimioterapia Adjuvante/métodos , Colo/patologia , Colo/cirurgia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluoruracila/análogos & derivados , Fluoruracila/uso terapêutico , Seguimentos , Humanos , Leucovorina/uso terapêutico , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Compostos Organoplatínicos/uso terapêutico , Cuidados Paliativos/métodos , Prognóstico , Reto/patologia , Reto/cirurgia , Análise de Sobrevida , Fator de Crescimento Transformador beta/metabolismo
16.
BMC Cancer ; 19(1): 423, 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31060542

RESUMO

BACKGROUND: The clinical behavior of prostate cancer (PCa) is variable, and while the majority of cases remain indolent, 10% of patients progress to deadly forms of the disease. Current clinical predictors used at the time of diagnosis have limitations to accurately establish progression risk. Here we describe the development of a tumor suppressor regulated, cell-cycle gene expression based prognostic signature for PCa, and validate its independent contribution to risk stratification in several radical prostatectomy (RP) patient cohorts. METHODS: We used RNA interference experiments in PCa cell lines to identify a gene expression based gene signature associated with Tmeff2, an androgen regulated, tumor suppressor gene whose expression shows remarkable heterogeneity in PCa. Gene expression was confirmed by qRT-PCR. Correlation of the signature with disease outcome (time to recurrence) was retrospectively evaluated in four geographically different cohorts of patients that underwent RP (834 samples), using multivariate logistical regression analysis. Multivariate analyses were adjusted for standard clinicopathological variables. Performance of the signature was compared to previously described gene expression based signatures using the SigCheck software. RESULTS: Low levels of TMEFF2 mRNA significantly (p < 0.0001) correlated with reduced disease-free survival (DFS) in patients from the Memorial Sloan Kettering Cancer Center (MSKCC) dataset. We identified a panel of 11 TMEFF2 regulated cell cycle related genes (TMCC11), with strong prognostic value. TMCC11 expression was significantly associated with time to recurrence after prostatectomy in four geographically different patient cohorts (2.9 ≤ HR ≥ 4.1; p ≤ 0.002), served as an independent indicator of poor prognosis in the four RP cohorts (1.96 ≤ HR ≥ 4.28; p ≤ 0.032) and improved the prognostic value of standard clinicopathological markers. The prognostic ability of TMCC11 panel exceeded previously published oncogenic gene signatures (p = 0.00017). CONCLUSIONS: This study provides evidence that the TMCC11 gene signature is a robust independent prognostic marker for PCa, reveals the value of using highly heterogeneously expressed genes, like Tmeff2, as guides to discover prognostic indicators, and suggests the possibility that low Tmeff2 expression marks a distinct subclass of PCa.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/diagnóstico , Neoplasias da Próstata/diagnóstico , Transcriptoma , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Progressão da Doença , Intervalo Livre de Doença , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Valor Preditivo dos Testes , Prognóstico , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/genética , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , RNA Mensageiro/metabolismo , Estudos Retrospectivos
17.
World J Surg Oncol ; 17(1): 80, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077193

RESUMO

OBJECTIVE: To investigate the predictive value of lymphovascular space invasion (LVSI) for nodal recurrence and overall survival (OS) in patients with stage I endometrioid endometrial cancer (EC) following surgical staging that included adequate lymph node sampling. METHODS: Retrospective analyses of patients undergoing surgical staging for FIGO stage I endometrioid EC between 1998 and 2015 were performed using an institutional database and the National Cancer Database (NCDB). Using the institutional database, logistic regression modeling identified predictors of nodal recurrence; Cox proportional hazards modeling was used to predict progression-free survival (PFS). Utilizing NCDB, Cox proportional hazards modeling was used to predict OS. The Kaplan-Meier method was used to estimate hazard ratios (HR). Survival curves were compared using the log-rank test. RESULTS: Among 275 institutional cases, LVSI was present in 48 (17.5%). There were 11 nodal recurrences: 18.8% (9/48) of cases with LVSI had a nodal recurrence compared to 0.88% (2/227) of those without LVSI. In multivariate analysis of institutional data, LVSI was the only significant predictor of nodal recurrence (p = 0.002). Among 28,076 NCDB cases, LVSI was present in 3766 (13.5%). In multivariate analysis of NCDB, grade 3, LVSI, and depth of invasion (all p <  0.001) were prognostic for OS after adjusting for adjuvant radiation. CONCLUSION: LVSI is an independent prognostic factor for nodal recurrence in stage I endometrial cancer with lymph node assessment. LVSI is associated with lower OS in NCDB. Given these findings, adjuvant therapy could be considered in these patients.


Assuntos
Adenocarcinoma/mortalidade , Carcinoma Endometrioide/mortalidade , Neoplasias do Endométrio/mortalidade , Linfonodos/patologia , Vasos Linfáticos/patologia , Recidiva Local de Neoplasia/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Idoso , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Terapia Combinada , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida
18.
Zhonghua Wai Ke Za Zhi ; 57(5): 366-372, 2019 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-31091592

RESUMO

Objective: To analyze the association between clinicopathological factors and clinical diagnosis, treatment and surgery of local regional recurrence (LRR) in breast cancer. Methods: A retrospective study was done to evaluate consecutive 7 823 breast cancer LRR cases between January 2009 and August 2018 at Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine. A total of 108 LRR patients were enrolled: 35 cases (32.4%) with ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery, 40 cases (37.0%) of chest wall recurrence (CR), and 33 cases (30.6%) with regional lymph node recurrence (LNR). All patients were female, aged from 26 to 83 years with a mean of 49 years. Clinicopathological factor and its relationship with different sites of LRR and following surgical choice were analyzed by χ(2) test, rank-sum test and Logistic regression. Survival analysis were performed between different LRR patterns and whether undergoing second surgery. Kaplan-Meier survival curves and Log-rank tests demonstrated the distribution of overall survival. Results: Both univariate analysis and multivariate analysis found that axillary lymph nodes (ALN) status (OR=7.27, 95% CI: 1.30 to 40.53, P=0.042) and disease-free interval (OR=0.18, 95% CI: 0.06 to 0.60, P=0.013) were related to different site of LRR. Compared with patients with IBTR, LNR and CR patients had a higher rate of ALN metastasis and a shorter disease-free interval. A total of 36 LRR patients underwent following surgery. In univariate analysis, initial ALN surgery (χ(2)=16.705, P=0.001), pathological type (χ(2)=7.047, P=0.03), ALN status (χ(2)=10.812, P=0.002), disease-free interval (χ(2)=6.118, P=0.023) and LRR site(χ(2)=19.328, P=0.000) were associated with surgical treatment for LRR patients. Multivariate analysis demonstrated that only site of LRR was independently associated with surgery (OR=0.17, 95% CI: 0.05 to 0.65, P=0.024). The 5-year overall survival was 100% and 60.1% (P=0.018) for LRR patients treated with surgery or not. Furthermore, CR patients had significantly worse overall survival than LNR and IBTR patients, with 5-year overall survival 53.1%, 73.5%, and 100% respectively (P=0.021). Conclusions: Initial lymph nodes metastasis and disease-free interval are associated with different site of LRR. LRR site significantly influenced following surgery choice after LRR, which are both related with overall survival after LRR.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Mastectomia Segmentar/efeitos adversos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , China , Intervalo Livre de Doença , Análise Fatorial , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Estudos Retrospectivos , Análise de Sobrevida , Parede Torácica/patologia
19.
Eur J Endocrinol ; 180(6): 387-396, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30991359

RESUMO

Objective Many patients with adrenocortical carcinoma (ACC) suffer from tumor recurrence despite radical surgery. Evidence on the post-operative use of mitotane is controversial and no predictors of response are available. We aimed to assess whether adjuvant mitotane treatment may prolong survival in patients with non-metastatic ACC following complete resection and whether ACC patients at high risk of recurrence may benefit from treatment. Design and methods We retrospectively reviewed data from 152 non-metastatic ACC patients followed at the San Luigi Gonzaga Hospital: 100 patients were treated with adjuvant mitotane and 52 patients were left untreated following surgery. We assessed a number of potential predictive factors of recurrence and death. Mitotane effect was explored stratifying patients by staging (stage I-II vs stage III), hormone secretion (yes vs no) and Ki67 index. Results The non-treated group had a higher risk of recurrence (HR: 2.79, 95%CI: 1.58-4.91; P < 0.001) than mitotane-treated group, while overall survival was not significantly different between groups. Hormone secretion, elevated Weiss score and elevated Ki67 index confer a higher risk of both recurrence and death and stage III ACC of death. Adjuvant mitotane treatment reduced significantly the risk of death in patients with elevated Ki67 index (P = 0.005) and in patients with stage III ACC (P = 0.02). Conclusions Adjuvant mitotane may prolong recurrence-free survival in radically resected ACC patients with acceptable toxicity and may also prolong overall survival in a subgroup of ACC patients at high risk of recurrence.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/tratamento farmacológico , Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Mitotano/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/mortalidade , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/mortalidade , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
20.
Medicine (Baltimore) ; 98(16): e14858, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31008921

RESUMO

F-18 fluorodeoxyglucose (FDG)-avid metastatic lesions are associated with a poor response to radioiodine ablation therapy (RIT) in papillary thyroid cancer (PTC). This study evaluated the significance of preablative FDG positron emission tomography (PET) for the assessment of risk factors and frequency of malignant FDG-avid lymph nodes in patients with PTC undergoing RIT.The study included 339 consecutive patients (mean age 46.3 ±â€Š12.5 y; 260 females) with PTC referred for the first RIT and who underwent routine preablative FDG PET between April 2011 and February 2013. FDG-avid lymph nodes (FALNs) were identified using retrospective image reviews. The frequency of malignant FALN (mFALN), its contribution to persistent or recurrent PTC, and its risk factors were analyzed.Among the patients, 112 had FALNs (33.0%): 11 mFALNs (3.2%) and 101 benign FALNs (bFALNs, 29.8%). mFALN contributed to 55% of persistent or recurrent PTC after RIT, which was observed in 20 of 339 patients (5.9%) during the post-RIT follow-up. Among preoperative risk factors, suspicious extrathyroidal extension and lateral neck lymph node metastasis on imaging studies were associated with mFALN. Among postoperative risk factors, T3/T4 and N1b stages, higher stimulated thyroglobulin, and higher numbers of metastatic lymph nodes and dissected lymph nodes, were associated with mFALN.mFALNs were observed in a small number of patients with PTC undergoing RIT, but it contributed 55% of total recurrent or persistent disease. Increased frequency of mFALNs is associated with more advanced PTC. Preablative FDG PET has value in evaluation of patients with RIT-resistant lesions and may help determine further treatment strategies.


Assuntos
Fluordesoxiglucose F18 , Metástase Linfática/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Tomografia por Emissão de Pósitrons/métodos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Feminino , Humanos , Radioisótopos do Iodo , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Compostos Radiofarmacêuticos , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Câncer Papilífero da Tireoide/mortalidade , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapia
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