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1.
Open Heart ; 10(1)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36914205

RESUMO

OBJECTIVE: The lifelong risks of cardiovascular disease following hypertensive disorders of pregnancy are well described. Awareness of these risks and associated health-seeking behaviours among affected individuals remains unclear. We aimed to assess participants' knowledge of their cardiovascular disease risk and relevant health-seeking behaviours following a pregnancy affected by preeclampsia or gestational hypertension. METHODS: We undertook a single-site, cross-sectional cohort study. The target population included individuals who birthed at a large tertiary referral centre in Melbourne, Australia, between 2016 and 2020, and were diagnosed with gestational hypertension or pre-eclampsia. Participants completed a survey assessing pregnancy details, medical comorbidities, knowledge of future risks and health-seeking behaviours post-pregnancy. RESULTS: 1526 individuals met inclusion criteria and 438 (28.6%) completed the survey. Of these, 62.6% (n=237) were unaware of their increased risk of cardiovascular disease following a hypertensive disorder of pregnancy. Participants who reported awareness of their increased risk were more likely to have annual blood pressure monitoring (54.6% vs 38.1%, p<0.01), and at least one assessment of blood cholesterol (p<0.01), blood glucose (p=0.03) and renal function (p=0.01). Participants who were aware were more likely to be taking antihypertensive medication (24.5% vs 6.6%, p<0.01) since pregnancy, compared with those who were unaware. There were no differences between groups in diet, exercise or smoking habits. CONCLUSION: Among our study cohort, risk awareness was associated with increased health-seeking behaviours. Participants who were aware of their increased risk of cardiovascular disease were more likely to have regular cardiovascular risk factor assessments. They were also more likely to be taking antihypertensive medication.


Assuntos
Doenças Cardiovasculares , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Complicações Cardiovasculares na Gravidez , Gravidez , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/tratamento farmacológico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/epidemiologia , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Complicações Cardiovasculares na Gravidez/epidemiologia , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Aceitação pelo Paciente de Cuidados de Saúde
2.
Head Neck ; 44(8): 1940-1947, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35642444

RESUMO

BACKGROUND: We have previously reported our early experience in robotic-assisted nasopharyngectomy. The current case series is a report of our experience in 33 robotic-assisted nasopharyngectomy. METHODS: Prospective series of patients who underwent robotic-assisted nasopharyngectomy for local recurrent nasopharyngeal carcinoma from January 2010 to March 2019. RESULTS: Thirty-one patients underwent robotic-assisted nasopharyngectomy with two additional second procedure for positive margin. Median age is 55 years (29-85). Twenty-five patients had rT1 disease and six patients had tumor invaded sphenoid floor (rT3). Median operative time was 227 min and median blood loss was 200 ml. The median follow-up period for all patients were 38 months. Four patients had local recurrence. Five-year local control rate, overall survival, and disease-free survival are 85.1%, 55.7%, and 69.1%, respectively. CONCLUSION: Robotic-assisted nasopharyngectomy for recurrent nasopharyngectomy was showed to have a high local control rate. The operating time was comparable to open surgery.


Assuntos
Neoplasias Nasofaríngeas , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/patologia , Faringectomia/métodos , Estudos Prospectivos , Terapia de Salvação/métodos , Taxa de Sobrevida
3.
Blood Cancer J ; 12(6): 96, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35750687

RESUMO

Chimeric antigen receptor-engineered T (CAR-T) cells have shown promising efficacy in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL). However, challenges remain including long manufacturing processes that need to be overcome. We presented the CD19-targeting CAR-T cell product GC007F manufactured next-day (FasTCAR-T cells) and administered to patients with R/R B-ALL. A total of 21 patients over 14 years of age with CD19+ R/R B-ALL were screened, enrolled and infused with a single infusion of GC007F CAR-T at three different dose levels. The primary objective of the study was to assess safety, secondary objectives included pharmacokinetics of GC007F cells in patients with R/R B-ALL and preliminary efficacy. We were able to demonstrate in preclinical studies that GC007F cells exhibited better proliferation and tumor killing than conventional CAR-T (C-CAR-T) cells. In this investigator-initiated study all 18 efficacy-evaluable patients achieved a complete remission (CR) (18/18, 100.00%) by day 28, with 17 of the patients (94.4%) achieving CR with minimal residual disease (MRD) negative. Fifteen (83.3%) remained disease free at the 3-month assessment, 14 patients (77.8%) maintaining MRD negative at month 3. Among all 21 enrolled patients, the median peak of CAR-T cell was on day 10, with a median peak copy number of 104899.5/µg DNA and a median persistence period of 56 days (range: 7-327 days). The incidence of cytokine release syndrome (CRS) was 95.2% (n = 20), with severe CRS occurring in 52.4% (n = 11) of the patients. Six patients (28.6%) developed neurotoxicity of any grade. GC007F demonstrated superior expansion capacity and a less exhausted phenotype as compared to (C-CAR-T) cells. Moreover, this first-in-human clinical study showed that the novel, next-day manufacturing FasTCAR-T cells was feasible with a manageable toxicity profile in patients with R/R B-ALL.


Assuntos
Linfoma de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Doença Aguda , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos Quiméricos/genética , Indução de Remissão , Linfócitos T
4.
Clin Cancer Res ; 27(5): 1242-1246, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33234511

RESUMO

PURPOSE: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027. PATIENTS AND METHODS: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. RESULT: Robust expansion of CAR-T cells along with rapid eradication of CD7+ T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed. CONCLUSIONS: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.


Assuntos
Antígenos CD7/imunologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Imunoterapia Adotiva/efeitos adversos , Nitrilas/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/patologia , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico , Adulto Jovem
5.
Laryngoscope Investig Otolaryngol ; 5(3): 468-472, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32596489

RESUMO

Nasopharyngeal carcinoma is endemic in southern parts of China including Hong Kong. Primary treatment entails radiotherapy ± chemotherapy depending on disease stage at presentation. Surgery is offered as a means of salvage for persistent and recurrent disease. Comprehensive preoperative work-up, careful patient selection, attention to details perioperation and multidisciplinary approach is essential in ensuring optimal outcomes after salvage surgery for recurrent nasopharyngeal carcinoma patients. Since the COVID-19 outbreak, we are faced with unprecedented challenges with priorities of care and resources being shifted to combat the virus. These include patient selection and timing of treatment, while preventing disease transmission to heath care providers. Practices and recommendations made in this document are intended to support safe clinical practice and efficient use of resources during this challenging time.

6.
Adv Otorhinolaryngol ; 83: 66-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30943506

RESUMO

It is not uncommon for patients with hypopharyngeal cancer to present at an advanced stage of disease. Surgical treatment provides a cure for the tumour with immediate relief from obstruction to the airway and the swallowing passage. Careful planning of surgery is important to ensure good outcome of treatment and prevent complications, some of which may be fatal. The shape of the hypopharynx resembles that of a funnel, with a wide circumference above in continuity with the oropharynx, and a small circumference below where it joins with the cervical oesophagus. As a result, while small tumours require the partial removal of the hypopharynx, large tumours, especially those involving the post-cricoid region, warrant a complete, circumferential pharyngectomy. For tumours that invade the cervical esophagus, transcervical approach is still feasible, and this is facilitated by the removal of the manubrium, allowing access to the tumour and resection with clear margins. In the presence of synchronous tumours lower down in the esophagus, pharyngo-laryngo-esophagectomy is indicated. Successful reconstruction of defects after tumour extirpation allows proper wound healing and early delivery of adjuvant radiotherapy. It is also important to ensure quick recovery of the long-term swallowing function. It ranges from the use of the soft tissue flap with skin island that is sutured as a patch to the remnants of the pharyngeal mucosa, to the use of a visceral flap, such as the free jejunal flap, to repair the circumferential pharyngectomy defects. The treatment protocol is personalized according to the extent of the tumour and the characteristics of the patients.


Assuntos
Neoplasias Hipofaríngeas/cirurgia , Hipofaringe/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/reabilitação , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Procedimentos Cirúrgicos Operatórios/métodos
7.
Oral Oncol ; 91: 85-91, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30926068

RESUMO

BACKGROUND: To study the efficacy of surgery for recurrent T3 nasopharyngeal carcinoma (NPC) and to determine the prognostic significance of various skull base bone invasion. METHOD: Retrospective view of the surgical outcome for recurrent T3 NPC. Kaplan Meier and log rank tests were used to determine the 5-year overall and disease specific survival. Multivariate analysis was used to identify significant independent prognostic factors that affect the surgical outcome. RESULTS: Between 1990 and 2017, 208 patients with recurrent T3 NPC were recruited. Salvage surgery was performed via the endoscopic endonasal approach (n = 22, 10.6%), endoscopic transpterygoid approach (n = 63, 30.3%) and the maxillary swing approach (n = 123, 59.1%). Thirty-eight (18.3%) patients required vascular bypass. The skull base bone involved by the tumours included: maxillary sinus (n = 13), clivus (n = 36), pterygoid process (n = 61), sphenoid sinus (n = 30), petrous part of the temporal bone (n = 42) and a combination of the above (n = 26). The mean follow-up duration was 41.7 months. Multivariate analysis identified tumours involving with both cortexes of the clivus and the lateral wall of the sphenoid sinus, as well as positive bone resection margins as the significant independent prognostic factors for surgical outcome. CONCLUSION: Outcome of surgical salvage is significantly worse for tumours that involve multiple bones at the skull base, particularly when both cortexes of the clivus and the lateral wall of the sphenoid sinus are invaded. Indication of aggressive surgery in such circumstances is controversial.


Assuntos
Neoplasias Ósseas/secundário , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/cirurgia , Recidiva Local de Neoplasia/patologia , Terapia de Salvação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Prognóstico , Estudos Retrospectivos
8.
Oral Oncol ; 78: 52-55, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29496058

RESUMO

BACKGROUND: To investigate the role of indocyanine green (ICG) lymphangiography in the reduction of drainage after neck dissection. METHODS: Patients with oral cavity squamous cell carcinoma were randomized into Group A (study group) and Group B (control). In the study group, upon the completion of neck dissection, a total of 2.5 mg of ICG was injected submucosally at the four quadrants around the tumour. Another 2.5 mg of ICG was injected subdermally in the groin bilaterally. The neck was screened using Near Infrared fluorescence. The presence of lymphatic leakage was noted and plicated with silk stitches. The total drainage volume of post-operative day 1, day 2 and the total accumulated volume until drain removal was measured. RESULTS: Twenty-two patients (Group A, n = 12; Group B, n = 10) were recruited. All patients in Group A had at least one site of lymphatic leakage identified. One patient in Group B developed chylous fistula and was excluded from analysis. The mean total drain output for day 1 and 2 after surgery, as well as the mean total output before drain removal, were significantly lower in Group A (22.4 ml vs. 86.2 ml [p = .02]; 14.2 ml vs. 72.8 ml [p = .02]; and 58.4 ml vs. 392 ml [p = .01], respectively), allowing earlier drain removal (2.2 days vs. 7.2 days, p = .02). CONCLUSIONS: Intra-operative ICG lymphangiography is useful in the reduction of drainage volume after neck dissection for caners in the head and neck region.


Assuntos
Drenagem , Verde de Indocianina/administração & dosagem , Linfonodos/patologia , Linfografia/métodos , Esvaziamento Cervical/efeitos adversos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias
9.
Head Neck ; 40(1): 103-110, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29083514

RESUMO

BACKGROUND: The purpose of this study was to assess the predictability of the American Joint Committee on Cancer (AJCC) staging system on patients with stage II recurrent nasopharyngeal carcinoma (NPC). METHOD: We conducted a retrospective review of the surgical outcome for patients with recurrent NPC and retropharyngeal lymph node (RLN) metastasis (group I), recurrent NPC and parapharyngeal space (PPS) invasion (group II), and recurrent NPC and internal carotid artery (ICA) encasement (group III). RESULTS: Between 1990 and 2013, 145 patients received an operation for stage II recurrent NPC (group I, n = 62; group II, n = 65; and group III, n = 18). The rate of local tumor recurrence was significantly higher in groups II and III. The rate of systemic metastasis was significantly higher in group III (16.7%). Accordingly, the 5-year overall survival was significantly worse for patients in group III (group I: 81.2%; group II: 68.4%; and group III: 48.5%). CONCLUSION: The significantly worse prognosis of recurrent NPC encasing the ICA warrants an upstage to the T3 classification in the current AJCC staging system.


Assuntos
Artérias Carótidas/patologia , Linfonodos/patologia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/patologia , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/radioterapia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Faringectomia/métodos , Tomografia por Emissão de Pósitrons/métodos , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
Laryngoscope ; 128(6): 1386-1391, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29114939

RESUMO

BACKGROUND: Prospective, observational study to assess the efficacy of salvage nasopharyngectomy for recurrent nasopharyngeal carcinoma (NPC) via the endoscopic endonasal approach using a three-dimensional (3D) high-definition endoscopic system. METHODS: Between 2016 and 2017, 30 patients with recurrent NPC were recruited. Patient demographics, tumor characteristics, and perioperative data were recorded. Instrument ergonomics and perceived advantages were assessed by the operating, assisting, and observing surgeons. RESULTS: The majority (70%) of patients received radiotherapy alone as the initial treatment for NPC, and tumor recurred after a mean interval of 16.8 months. The tumor (T) classifications of the recurrent (R) tumors were: RT1: 46.7%; RT2: 33.3%; and RT3: 20.0%. The mean operative time was 293.3 minutes, and no conversion to open approach was necessary. Internal carotid artery dissection was required in nine patients, and the resection and repair of dura was required in six patients. The most common method of reconstruction was free vastus lateralis flap (46.7%). Microscopically clear resection margins were achieved in 73.3% of patients. The mean hospital stay was 6.8 days. There was no hospital mortality. One patient developed minor secondary hemorrhage, whereas the other developed transient contralateral vocal cord paralysis. On quantitative assessment, surgeons noticed a significant advantage of the 3D system with regard to depth and size perception, anatomy identification, and hand-eye coordination, whereas there was no significant difference in terms of strain sensation and dizziness. CONCLUSION: The 3D high-definition endoscopic system improves the precision of endoscopic nasopharyngectomy, particularly when dissection of the internal carotid artery and dura is required. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1386-1391, 2018.


Assuntos
Carcinoma/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Faringectomia/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Feminino , Humanos , Imageamento Tridimensional/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Recidiva Local de Neoplasia/cirurgia , Faringectomia/efeitos adversos , Estudos Prospectivos , Terapia de Salvação/efeitos adversos , Resultado do Tratamento
11.
Oral Oncol ; 72: 194-196, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28720420

RESUMO

BACKGROUND: To report on the feasibility of total laryngopharyngectomy and free jejunal flap transfer for patient with hypopharyngeal cancer via the transoral robotic surgery (TORS) approach. MATERIAL AND METHODS: A patient with hypopharyngeal cancer involving the post-cricoid region is used for demonstration of the TORS total laryngopharyngectomy and free jejunal flap reconstruction. RESULTS: The procedure starts with a cruciate incision for terminal tracheostomy. The trachea and cervical esophagus is exposed and transected, making sure that the resection margins are adequate. This is followed by the transoral dissection using the robotic surgical system. The laryngopharyngectomy specimen is delivered and the free jejunal flap is replaced transorally. Jejuno-oesophageal suturing and the microvascular anastomosis are performed through the tracheostomy wound. The remaining pharyngo-jejunal anastomosis is performed transorally via the TORS approach. CONCLUSION: TORS total laryngopharyngectomy and free jejunal flap reconstruction is feasible and provides and alternative option to the traditional transcervical approach.


Assuntos
Cicatriz , Retalhos de Tecido Biológico , Neoplasias Hipofaríngeas/cirurgia , Jejuno/cirurgia , Laringectomia/métodos , Faringectomia/métodos , Procedimentos de Cirurgia Plástica/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Humanos , Laringectomia/efeitos adversos , Dor Pós-Operatória/etiologia , Faringectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Traqueostomia/métodos
12.
Chin J Cancer ; 35(1): 95, 2016 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-27852288

RESUMO

BACKGROUND: Programmed cell death protein 4 (PDCD4) is a novel tumor suppressor protein involved in programmed cell death. Its association with cancer progression has been observed in multiple tumor models, but evidence supporting its association with solid tumors in humans remains controversial. This study aimed to determine the clinical significance and prognostic value of PDCD4 in solid tumors. METHODS: A systematic literature review was performed to retrieve publications with available clinical information and survival data. The eligibility of the selected articles was based on the criteria of the Dutch Cochrane Centre proposed by the Meta-analysis Of Observational Studies in Epidemiology group. Pooled odds ratios (ORs), hazard ratios (HRs), and 95% confidence intervals (CIs) for survival analysis were calculated. Publication bias was examined by Begg's and Egger's tests. RESULTS: Clinical data of 2227 cancer patients with solid tumors from 23 studies were evaluated. PDCD4 expression was significantly associated with the differentiation status of head and neck cancer (OR 4.25, 95% CI 1.87-9.66) and digestive system cancer (OR 2.87, 95% CI 1.84-4.48). Down-regulation of PDCD4 was significantly associated with short overall survival of patients with head and neck (HR: 3.44, 95% CI 2.38-4.98), breast (HR: 1.86, 95% CI 1.36-2.54), digestive system (HR: 2.12, 95% CI 1.75-2.56), and urinary system cancers (HR: 3.16, 95% CI 1.06-9.41). CONCLUSIONS: The current evidence suggests that PDCD4 down-regulation is involved in the progression of several types of solid tumor and is a potential marker for solid tumor prognoses. Its clinical usefulness should be confirmed by large-scale prospective studies.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias/patologia , Proteínas de Ligação a RNA/metabolismo , Proteínas Reguladoras de Apoptose/genética , Biomarcadores Tumorais/genética , Progressão da Doença , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Ligação a RNA/genética
13.
Oncotarget ; 7(36): 58218-58233, 2016 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-27533461

RESUMO

MicroRNA controls cancer invasion by governing the expression of gene regulating migration and invasion. Here, we reported a novel regulatory pathway controlled by miR-744-3p, which enhanced expression of matrix metallopeptidase 9 (MMP-9) in laryngeal squamous cell carcinoma (LSCC). We profiled the differential micoRNA expression pattern in LSCC cell lines and normal epithelial cultures derived from the head and neck mucosa using microRNA microarray. MiR-7-1-3p, miR-196a/b and miR-744-3p were expressed differentially in the LSCC cell lines. Subsequent validation using real-time PCR revealed that high miR-744-3p level was positively correlated with regional lymph node metastasis of LSCC. Real-time cellular kinetic analysis showed that suppressing miR-744-3p could inhibit migration and invasion of LSCC cell lines and reduce the number of lung metastatic nodules in nude mice modules. In silico analysis revealed that miR-744-3p targeted 2 distinct signaling cascades which eventually upregulated MMP-9 expression in LSCC. First, miR-744-3p could suppress programmed cell death 4 (PDCD4), a direct suppressor of NF-κB (p65). PDCD4 could also prevent AKT activation and suppress MMP-9 expression. Further, suppressing miR-744-3p expression could restore phosphatase and tensin homolog (PTEN) expression. PTEN could inhibit AKT activation and inhibit MMP-9 expression in LSCC cells. The results revealed that suppressing miR-744-3p was effective to inhibit LSCC metastasis by inactivating AKT/mTOR and NF-κB (p65) signaling cascade. Targeting miR-744-3p could be a valuable therapeutic intervention to suppress the aggressiveness of LSCC.


Assuntos
Proteínas Reguladoras de Apoptose/genética , Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Neoplasias Pulmonares/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , Proteínas de Ligação a RNA/genética , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Neoplasias Laríngeas/patologia , Laringe/patologia , Pulmão/patologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Linfática , Camundongos , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oncogenes , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Serina-Treonina Quinases TOR/metabolismo , Fator de Transcrição RelA/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Head Neck ; 38 Suppl 1: E1404-12, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26566179

RESUMO

BACKGROUND: The purpose of this study was to investigate the oncologic outcome and quality of life after surgical treatment of locally advanced (rT3-rT4) recurrent nasopharyngeal carcinoma (NPC) using the staged extracranial/intracranial vascular bypass and combined craniofacial approach. METHODS: We conducted a prospective study. RESULTS: Between 1998 and 2013, 28 patients with rT3 to rT4 tumors were treated with the proposed surgical protocol. Clear resection margin was achieved in 46.4%. The median follow-up was 42.6 months. The rate of local recurrence was 17.8%. The 5-year overall survival was 52%. There was no change in the mean global health system score after the extensive surgery, although the physical functioning scores deteriorated significantly. The most common symptoms experienced by patients were speech and swallowing problems. CONCLUSION: The proposed surgical treatment for locally advanced recurrent NPC was associated with satisfactory local tumor control and survival. Quality of life after surgery was reasonable, although multidisciplinary training was required to maximize the postoperative speech and swallowing function. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1404-E1412, 2016.


Assuntos
Carcinoma/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Qualidade de Vida , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Estudos Prospectivos
15.
Head Neck ; 38 Suppl 1: E594-9, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-25783024

RESUMO

BACKGROUND: The purpose of this study was to present the postoperative local tumor control and survival with regard to the different resection margin statuses during salvage nasopharyngectomy. METHODS: We conducted a whole-organ study of nasopharyngectomy specimens. RESULTS: Between 2005 and 2010, 126 patients underwent maxillary swing nasopharyngectomy. The T classification of the recurrent tumor was: T1, 23.8%; T2, 41.3%; T3, 28.6%; and T4, 6.3%. The chance of clear, close, and involved resection margins at nasopharyngectomy was 44.4%, 31.0%, and 24.6%, respectively. At follow-up, the corresponding risk of local tumor recurrence after surgery was 10.7%, 38.5%, and 67.7%, respectively. The local tumor control was significantly worse in patients with involved margins compared with those with close margins (p = .01), which was, in turn, significantly worse than those with clear margins (p = .04). CONCLUSION: The primary objective of salvage nasopharyngectomy is to achieve clear resection margins. Close and involved margins result in significantly inferior local tumor control and overall survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E594-E599, 2016.


Assuntos
Carcinoma/cirurgia , Margens de Excisão , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Terapia de Salvação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Faringectomia , Estudos Retrospectivos
16.
Rhinology ; 53(3): 204-11, 2015 09.
Artigo em Inglês | MEDLINE | ID: mdl-26363161

RESUMO

INTRODUCTION: Curative resection of malignant tumours of the skull base is increasingly undertaken endoscopically. Hitherto the diverse histology, rarity and long natural history have made it difficult to accrue statistically robust cohorts for comparison with conventional craniofacial resection. It is now possible to make such a comparison in a large personal cohort. METHOD: Data on all cases of sinonasal malignancy undergoing endoscopic resection with curative intent over an eighteen year period were collected prospectively and analysed for survival and prognostic factors. RESULTS: There were 140 cases, 68 men and 72 women, aged 20-92 years (mean 63 yrs). Follow-up ranged from 6-184 months (mean 60 months). Eighteen different histopathologies were represented with olfactory neuroblastoma (36), malignant melanoma (33) and adenocarcinoma (19) being the commonest. Additional radiotherapy was given in 95 cases and chemotherapy in 49. Overall survival is 84% at 5 years and 69% at 10 years. Overall disease-free survival was 77% at 5 years and 56% at ten. Overall and disease-free survival at 5 (and 10) years is, respectively, 97% and 90% for olfactory neuroblastoma, 79% and 68% for adenocarcinoma and 56% and 39% for malignant melanoma. CONCLUSION: These results show that endoscopic resection is an alternative to conventional craniofacial resection in selected cases.


Assuntos
Carcinoma/cirurgia , Endoscopia , Estesioneuroblastoma Olfatório/cirurgia , Melanoma/cirurgia , Neoplasias Nasais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Estudos de Coortes , Feminino , Humanos , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Cavidade Nasal , Neoplasias Nasais/mortalidade , Neoplasias Nasais/patologia , Seios Paranasais , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Otolaryngol Head Neck Surg ; 153(3): 379-84, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26138607

RESUMO

OBJECTIVE: To investigate the incidence of occult nodal metastasis and severity of shoulder dysfunction after selective neck dissection (SND) for recurrent nasopharyngeal carcinoma (NPC) with N0 status. STUDY DESIGN: Prospective, single-group, pre/post test design. SETTING: Academic medical center. SUBJECTS AND METHODS: Between 1998 and 2012, 46 patients who had recurrent NPC and N0 status were recruited. They subsequently received salvage nasopharyngectomy and SND, removing ipsilateral level I to III and V lymphatics. The incidence of occult nodal metastasis was noted. All patients underwent standardized physiotherapy after surgery. Postoperative shoulder function was measured using the Disability of Arm, Shoulder, and Hand (DASH) questionnaire. RESULTS: The incidence of microscopic nodal metastasis was 15.2%. For first year posttreatment, the mean DASH score was 44.2. With time, there was no improvement in shoulder function despite targeted physiotherapy (P = .09), and the second postoperative year mean DASH score was 46.3. The degree of daily activity affected was rated as moderate to very limited, and 30% of the patients had at least moderate shoulder pain at rest. CONCLUSION: Shoulder dysfunction after SND for recurrent NPC is significant and persistent. Given the low incidence of microscopic nodal metastasis in such circumstances, routine SND is not recommended.


Assuntos
Neoplasias Nasofaríngeas/cirurgia , Esvaziamento Cervical/efeitos adversos , Recidiva Local de Neoplasia/cirurgia , Ombro/fisiopatologia , Atividades Cotidianas , Carcinoma , Avaliação da Deficiência , Feminino , Hong Kong , Humanos , Incidência , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/patologia , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Medição da Dor , Faringectomia , Modalidades de Fisioterapia , Estudos Prospectivos , Terapia de Salvação , Retalhos Cirúrgicos
18.
Cancer ; 121(14): 2358-66, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25955785

RESUMO

BACKGROUND: Local recurrence is the major cause of treatment failure in patients who undergo surgical salvage of recurrent nasopharyngeal carcinoma (NPC) after radiotherapy. The authors investigated the role of Epstein-Barr virus (EBV)-encoded Bam HI-A rightward transcript 7 microRNA (BART7) status in resection margins in the identification of a subgroup of patients who may benefit from adjuvant reradiation after surgery. METHODS: One hundred two consecutive patients who had histologically clear resection margins after undergoing nasopharyngectomy for recurrent NPC were studied. The status of EBV microRNA BART7 in resection margins was investigated and correlated with the pattern of subsequent disease recurrence. RESULTS: After a median follow-up of 64 months, 20 patients (19.6%) developed local recurrence after surgery despite histologically uninvolved margins. The risk of local recurrence in patients with histologically close (<5 mm) and clear (≥5 mm) margins was 31.6% and 12.5%, respectively. In patients with clear histologic margins, those with margins that were positive for EBV microRNA BART7 has a significantly higher chance of developing local tumor recurrence (P = .016) than those with negative molecular margins. The difference was not significant when the histologic clearance at the resection margins was <5 mm. CONCLUSIONS: Tissue EBV microRNA BART7 is useful for identifying a subgroup of patients with histologically clear margins who are at increased risk of subsequent local tumor recurrence. Postoperative adjuvant treatment is warranted for these patients.


Assuntos
Proteínas de Transporte/genética , Procedimentos Cirúrgicos Nasais , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/cirurgia , Faringectomia , Terapia de Salvação/métodos , Adulto , Idoso , Carcinoma , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , MicroRNAs , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/virologia , Recidiva Local de Neoplasia/virologia , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Fatores de Transcrição
19.
Head Neck ; 37(12): E169-73, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25784055

RESUMO

BACKGROUND: The purpose of this study was to present the feasibility of indocyanine green (ICG) mapping of sentinel lymph node in recurrent nasopharyngeal carcinoma (NPC). M1ETHODS: Peritumoral injection of 5-mg ICG solution and real-time mapping of the sentinel lymph nodes in the neck was performed during surgery. The sentinel lymph node identified was excised and sent separately for laboratory analysis. Selective neck dissection was then performed. The number and level of the sentinel lymph nodes, their signal-to-background ratio, and the histopathology of the sentinel lymph nodes and the neck dissection specimens were studied. RESULTS: A total of 5 patients were recruited into this study, of which 9 sentinel lymph nodes were identified. The majority of them were located in level II. The mean detection time after ICG injection was 288 seconds. The sentinel lymph nodes in 3 patients tested positive for malignancy. None of the selective neck dissection specimens harbored microscopic tumor deposits. CONCLUSION: ICG mapping of sentinel lymph nodes in locally recurrent NPC is potentially feasible. It offers a better nodal staging in patients with clinically N0 disease status.


Assuntos
Corantes/administração & dosagem , Verde de Indocianina/administração & dosagem , Imageamento por Ressonância Magnética , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/cirurgia , Esvaziamento Cervical , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Biópsia de Linfonodo Sentinela , Adulto , Índice de Massa Corporal , Carcinoma , Estudos de Viabilidade , Feminino , Fluorescência , Humanos , Cuidados Intraoperatórios , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/radioterapia , Esvaziamento Cervical/métodos , Recidiva Local de Neoplasia/radioterapia , Reprodutibilidade dos Testes , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento
20.
Head Neck ; 37(6): 788-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24604758

RESUMO

BACKGROUND: Minimally invasive nasopharyngectomy with the da Vinci surgical robot has been shown to be a feasible operation for salvage of recurrent nasopharyngeal carcinoma. The current case series presents the early results of robotic nasopharyngectomy. METHODS: We conducted a prospective series of patients who underwent robotic nasopharyngectomy for recurrent nasopharyngeal carcinoma in a single institution. RESULTS: Twelve patients underwent robotic nasopharyngectomy. The median operating time was 225 minutes. Median follow-up time was 23.8 months. Nine patients had clear resection margins, 2 patients had close margins, and 1 patient had positive margin. Two patients developed local recurrence and 1 patient had distant metastasis. Two patients in the cohort died of unrelated causes. The 2-year local control rate was 86%. The 2-year overall survival and disease-free survival was 83% and 61%, respectively. CONCLUSION: Early results of robotic nasopharyngectomy showed a high local control rate. The operating time was comparable to open surgery and morbidities were low.


Assuntos
Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Faringectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Duração da Cirurgia , Dor Pós-Operatória/fisiopatologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Terapia de Salvação/métodos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
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