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1.
Artigo em Inglês | MEDLINE | ID: mdl-38635282

RESUMO

Importance: Closure technique for optimization of postoperative and functional outcomes following salvage laryngectomy remains an area of debate among head and neck surgeons. Objective: To investigate the association of salvage laryngectomy closure technique with early postoperative and functional outcomes. Design, Setting, and Participants: This retrospective cohort study included patients from 17 academic, tertiary care centers who underwent total laryngectomy with no or limited pharyngectomy after completing a course of definitive radiotherapy or chemoradiotherapy with curative intent between January 2011 and December 2016. Patients with defects not amenable to primary closure were excluded. Data were analyzed from February 14, 2021, to January 29, 2024. Exposures: Total laryngectomy with and without limited pharyngectomy, reconstructed by primary mucosal closure (PC), regional closure (RC), or free tissue transfer (FTT). Main Outcomes and Measures: Patients were stratified on the basis of the pharyngeal closure technique. Perioperative and long-term functional outcomes were evaluated with bivariate analyses. A multivariable regression model adjusted for historical risk factors for pharyngocutaneous fistula (PCF) was used to assess risk associated with closure technique. Relative risks (RRs) with 95% CIs were determined. Results: The study included 309 patients (256 [82.8%] male; mean age, 64.7 [range, 58.0-72.0] years). Defects were reconstructed as follows: FTT (161 patients [52.1%]), RC (64 [20.7%]), and PC (84 [27.2%]). A PCF was noted in 36 of 161 patients in the FTT group (22.4%), 25 of 64 in the RC group (39.1%), and 29 of 84 in the PC group (34.5%). On multivariable analysis, patients undergoing PC or RC had a higher risk of PCF compared with those undergoing FTT (PC: RR, 2.2 [95% CI, 1.1-4.4]; RC: RR, 2.5 [95% CI, 1.3-4.8]). Undergoing FTT was associated with a clinically meaningful reduction in risk of PCF (RR, 0.6; 95% CI, 0.4-0.9; number needed to treat, 7). Subgroup analysis comparing inset techniques for the RC group showed a higher risk of PCF associated with PC (RR, 1.8; 95% CI, 1.1-3.0) and predominately pectoralis myofascial flap with onlay technique (RR, 1.9; 95% CI, 1.2-3.2), but there was no association of pectoralis myocutaneous flap with cutaneous paddle interposition with PCF (RR, 1.2; 95% CI, 0.5-2.8) compared with FTT with cutaneous inset. There were no clinically significant differences in functional outcomes between the groups. Conclusion and Relevance: In this study of patients with limited pharyngeal defects, interpositional fasciocutaneous closure technique was associated with reduced risk of PCF in the salvage setting, which is most commonly achieved by FTT in academic practices. Closure technique was not associated with functional outcomes at 1 and 2 years postoperatively.

2.
Am J Otolaryngol ; 45(3): 104141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38194889

RESUMO

OBJECTIVES: Virtual Surgical Planning (VSP) creates individualized surgical plans for free flap reconstruction of mandibular defects. Prior studies indicate that VSP can offer cost benefits due to reduced operative time and length of stay (LOS). We assessed the impact of VSP in the context of a validated postoperative abbreviated LOS clinical pathway. METHODS: This study assessed patients undergoing VSP vs conventional fibular free flap reconstruction for mandibular defects (12/2015-10/2020) and their operative time, ischemia time, and LOS were evaluated. RESULTS: Forty-four patients underwent VSP reconstruction, while 52 patients underwent conventional reconstruction for mandibular defects. VSP was associated with significantly lower total operative time (6 h and 57 mins vs 7 h and 54 mins, p = 0.011), but not length of stay or ischemia time. Total OR time was significantly increased with increasing number of segments needed in both the VSP group (p = 0.002) and the conventional group (p = 0.015). CONCLUSION: Shorter operative times and LOS have been attributed to the use of VSP in free tissue transfers. It is argued that these reductions offset the added cost of VSP. Our study indicates that there is no cost benefit for VSP utilization due to a significantly reduced operative time with no impact on length of admission in an abbreviated admission clinical pathway following free tissue transfer.


Assuntos
Retalhos de Tecido Biológico , Tempo de Internação , Reconstrução Mandibular , Duração da Cirurgia , Cirurgia Assistida por Computador , Humanos , Reconstrução Mandibular/métodos , Masculino , Feminino , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Cirurgia Assistida por Computador/métodos , Idoso , Adulto , Procedimentos Clínicos , Fíbula/transplante
3.
Laryngoscope ; 134(2): 684-687, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37462362

RESUMO

OBJECTIVE: The vascular anatomy of the proximal subscapular artery has been previously classified into 2 major types depending on the presence of a common subscapular trunk. The purpose of this study was to determine the utility, reliability, and cost of routine chest imaging to identify these anatomical variations. METHODS: Data were collected retrospectively at a tertiary medical center for patients who were undergoing CT chest for various indications between October 2019 and October 2020. Two independent and blinded readers interpreted CT chest with contrast of 52 patients for a total 104 sides. RESULTS: The proximal branching pattern of the subscapular system was identified to have a common trunk in 99 (95%) sides. The remaining five sides (5%) demonstrated two arterial pedicles; with one patient exhibiting the variant anatomy bilaterally. CONCLUSION: Preoperative CT chest with contrast can accurately identify anatomic variation of the subscapular vascular system. For complex reconstruction requiring a single anastomosis in the vessel depleted neck, preoperative imaging can assure selection of a type I vascular anatomy of the proximal subscapular system. Preoperative imaging with contrasted CT has value in assessing this anatomy when planning for chimeric flaps involving circumflex scapular and thoracodorsal arteries. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:684-687, 2024.


Assuntos
Cardiopatias Congênitas , Escápula , Retalhos Cirúrgicos , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Retalhos Cirúrgicos/irrigação sanguínea , Escápula/diagnóstico por imagem , Tomografia Computadorizada por Raios X
4.
Laryngoscope ; 134(4): 1642-1647, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37772913

RESUMO

OBJECTIVES: Microvascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti-fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes. METHODS: Retrospective review of reconstruction for IFS (2010-2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed. RESULTS: Twenty-seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing. CONCLUSION: Patients with maxillectomy defects from IFS can undergo microvascular-free flap reconstruction with good outcomes while on anti-fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1642-1647, 2024.


Assuntos
Retalhos de Tecido Biológico , Infecções Fúngicas Invasivas , Seios Paranasais , Procedimentos de Cirurgia Plástica , Sinusite , Humanos , Retalhos de Tecido Biológico/irrigação sanguínea , Ossos Faciais , Sinusite/cirurgia , Sinusite/microbiologia , Estudos Retrospectivos
5.
Am J Otolaryngol ; 45(2): 104095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38039915

RESUMO

INTRODUCTION: Living in disadvantaged neighborhoods has been shown to result in worse healthcare outcomes. The Area Deprivation Index (ADI) is a metric that ranks neighborhoods by socioeconomic disadvantage utilizing numerous factors including income, education, employment, and housing quality. METHODS: A retrospective review of all patients who underwent surveillance in an APP-led head and neck cancer survivorship clinic from Dec 2016 to Oct 2020 at an academic tertiary care center were included. Tumor characteristics, visit frequency, recurrence, number of missed appointments, loss of follow up, and ADI scores were collected. RESULTS: 543 patients were included in the study. A majority were male (69.9 %) and white race (84.9 %) with an average age of 64.6 years old. Average ADI national percentile score was 71.6(range: 17 to 100). ADI national percentile score was not predictive of tumor characteristics at initial presentation: lymphovascular invasion (p = 0.940; OR 1.0 [95 % CI: 0.9 to 1.1]), extranodal extension (p = 0.576; OR 1.0 [95 % CI: 0.9 to 1.2]), positive margins (p = 0.069; OR 0.9 [95 % CI: 0.9 to 1.0]). ADI national percentile score was not significantly correlated with loss to follow up (p = 0.153; OR 1.2 [95 % CI: 0.9 to 1.7] or cancer recurrence (p = 0.594; OR 1.0 [95 % CI: 0.9 to 1.1]). Missing one or more clinic visits was correlated with loss to follow up (p = 0.029; OR 13.1 [95 % CI: 1.3 to 131.7]. CONCLUSION: Living in a disadvantaged neighborhood did not correlate with negative tumor characteristics, loss to follow up, or recurrence within an APP-led survivorship head and neck cancer clinic.


Assuntos
Neoplasias de Cabeça e Pescoço , Sobrevivência , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Seguimentos , Instituições de Assistência Ambulatorial , Assistência Ambulatorial , Neoplasias de Cabeça e Pescoço/terapia , Estudos Retrospectivos
6.
Head Neck Pathol ; 17(3): 851-854, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37594632

RESUMO

BACKGROUND: BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene that is altered in a variety of neoplasms as well as in BAP1 tumor predisposition syndrome. BAP1 alterations are associated with aggressive behavior in some malignancies and may have treatment implications in future. We present the first documented case of loss of BAP1 protein expression by immunohistochemistry in the salivary duct carcinoma (SDC) component of an intracapsular carcinoma ex pleomorphic adenoma (CXPA) in the context of molecular loss of function of BAP1 in the neoplasm. METHODS: A woman of approximately 55 years of age presented with a deep parotid lobe mass, which was resected and found to be CXPA. BAP1 immunohistochemistry and next-generation sequencing was performed to further characterize the neoplasm. RESULTS: The neoplasm showed loss of BAP1 protein expression in the SDC component but retention in the residual pleomorphic adenoma (PA). Next-generation sequencing confirmed a BAP1 loss of function alteration in the neoplasm. CONCLUSION: This is the first documented case report of BAP1 protein expression loss in the SDC component of a CXPA. Future studies are needed to investigate the relevance of BAP1 alterations in SDC and CXPA, which may have prognostic and treatment implications.


Assuntos
Adenocarcinoma , Adenoma Pleomorfo , Carcinoma Ductal , Neoplasias das Glândulas Salivares , Feminino , Humanos , Adenoma Pleomorfo/genética , Glândula Parótida , Imuno-Histoquímica , Ductos Salivares , Neoplasias das Glândulas Salivares/genética , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética
7.
Am J Surg ; 225(6): 988-993, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36639303

RESUMO

BACKGROUND: With recent efforts to decrease opioid use following surgery, this study aims to answer: what pain regimen do patients follow at home? Is it controlling pain? METHODS: This is a prospective, pilot study of thyroid and parathyroid surgery patients. Patients were prescribed acetaminophen, ibuprofen, and tramadol dispensed in smart pill (Pillsy) bottles that record "events" corresponding to medication use. Patients received messages querying their current pain level. Patients were compared to historical controls. RESULTS: 26 patients were in the Pillsy group and 30 in the control group. In the Pillsy group, pain scores averaged 3.67 out of 10 in the first 24 h after surgery and decreased each day. Patients took an average of 6.45 doses of acetaminophen, 6.64 doses of ibuprofen, and 1.82 doses of tramadol in the first week. CONCLUSIONS: Pain scores are highest in the first 24 h after surgery and decrease thereafter. This acceptable level of pain can be achieved with non-opioid medications.


Assuntos
Acetaminofen , Tramadol , Humanos , Acetaminofen/uso terapêutico , Ibuprofeno/uso terapêutico , Tramadol/uso terapêutico , Glândula Tireoide , Estudos Prospectivos , Analgésicos Opioides/uso terapêutico , Projetos Piloto , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle
8.
Maxillofac Plast Reconstr Surg ; 41(1): 30, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31413961

RESUMO

BACKGROUND: Advancements in the field of microvascular surgery and the widespread adoption of microvascular surgical techniques have made the use of osteocutaneous fibula free flaps the standard of care in the surgical management of segmental mandibular defects. Although the literature possesses abundant evidence to support the effectiveness of fibula free flaps as a reconstructive method, there are relatively few studies reporting on outcomes as objectively measured by videofluoroscopic swallowing studies (VFSS). The purpose of this study is to explore the potential correlation between early postoperative VFSS and the long-term swallowing outcomes in patients who underwent mandibular reconstruction with fibula free flaps. METHODS: We performed a retrospective chart review of 36 patients who underwent mandibular reconstruction with osteocutaneous fibular free flaps between 2009 and 2012. Demographics, clinical variables, VFSS data, and diet information were retrieved. Penetration and aspiration findings on VFSS, long-term oral feeding ability, and the need for gastrostomy tube were statistical endpoints correlated with postoperative clinical outcomes. RESULTS: Thirty-six patients were reviewed (15 females and 21 males) with a mean age of 54 years (7-81). Seventeen cases were treated for malignancy. The size of the bony defect ranged from 3 to 15 cm (mean = 9 cm). The cutaneous paddle, a surrogate for soft tissue defect, ranged from 10 to 125 cm2 (mean = 52 cm2). A gastrostomy tube was present in patients preoperatively (n = 8), and postoperatively (n = 14). Seventeen patients had neoadjuvant exposure to radiation. Postoperative VFSS showed penetration in 13 cases (36%) and aspiration in seven (19%). Overall, 29 patients (80.6%) achieved unrestricted diet, and this was statistically correlated with age (p = 0.037), radiation therapy (p = 0.002), and preoperative gastrostomy tube (p = 0.03). The presence of penetration or aspiration on VFSS was a strong predictor for long-term unrestricted oral diet (p < 0.001). CONCLUSION: Early postoperative VFSS is an excellent predictor for long-term swallowing outcomes in patients undergoing mandibular reconstruction with osteocutaneous fibula free flaps.

9.
Otolaryngol Head Neck Surg ; 161(1): 91-97, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30912990

RESUMO

OBJECTIVE: To evaluate outcomes of free flaps in low- versus high-risk American Society of Anesthesiologists (ASA) classes utilizing a standardized perioperative clinical pathway. STUDY DESIGN: Case series with chart review. SETTING: Single tertiary care academic institution. SUBJECTS AND METHODS: Data were collected from 301 patients who underwent 305 free flap reconstructions for head and neck defects from January 2012 to March 2016 by a single surgeon (M.M.). A standardized perioperative clinical pathway was utilized for all patients, aimed at abbreviating hospital stay and minimizing intensive care unit stay. Data included ASA classification, comorbidities, length of hospitalization, intensive care unit stay, 30-day mortality/readmission, discharge disposition, flap survival, and postoperative complications. Low-risk ASA classes were defined as 1 and 2 (n = 53) and high risk as 3 and 4 (n = 248). RESULTS: Total medical complication rates (P = .012) were mildly increased in the high-risk group, as a result of increased minor-not major-medical complication rates (P = .007). Discharge to a nursing or rehabilitation facility was found to be more common in the high-risk group (P = .024). All other outcomes were not statistically different between the cohorts. CONCLUSION: The ASA classification system is a validated tool in determining perioperative risk. We found that minor medical complications and discharge to a rehabilitation/nursing facility were increased in the high-risk ASA classes; otherwise, there were no statistical differences between the groups. These findings suggest that the ASA classification may be helpful for preoperative discharge planning and counseling but should not be used for patient selection or to assess candidacy for the procedure.


Assuntos
Retalhos de Tecido Biológico , Cabeça/cirurgia , Indicadores Básicos de Saúde , Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Arkansas/epidemiologia , Comorbidade , Procedimentos Clínicos/normas , Feminino , Sobrevivência de Enxerto , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
10.
Head Neck ; 41(4): 982-992, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30652368

RESUMO

BACKGROUND: Assess the impact of a clinical pathway and progressive care unit (CPW/PCU) for patients undergoing head and neck free flap reconstruction with regard to patient outcomes and resource utilization. METHODS: Retrospective chart review of 270 patients at an academic tertiary-care center (2009-2014). Outcomes were compared among a control, CPW/PCU transition, and CPW/PCU groups. RESULTS: Compared to control, the CPW/PCU group had significantly reduced medical complications (21.1%-4.1%), intensive care unit length of stay (LOS, 5.02-0.2 days), hospital LOS (10.5-6.2 days), standardized total charges ($88 270-$58 661), and hospital costs ($41 365-$22 680). There were no observed differences in flap viability, surgical complications, reoperations, or readmissions. The CPW/PCU group achieved 100% home discharge. CONCLUSIONS: Our proposed CPW significantly improved patient outcomes and reduced resource utilization while maintaining flap outcomes. We propose a dynamic model for resource allocation that is easily reproducible in both academic and nonacademic settings.


Assuntos
Procedimentos Clínicos , Retalhos de Tecido Biológico/transplante , Neoplasias de Cabeça e Pescoço/cirurgia , Recursos em Saúde/estatística & dados numéricos , Tempo de Internação/economia , Procedimentos de Cirurgia Plástica/métodos , Centros Médicos Acadêmicos , Idoso , Análise de Variância , Estudos de Coortes , Bases de Dados Factuais , Feminino , Retalhos de Tecido Biológico/irrigação sanguínea , Rejeição de Enxerto , Sobrevivência de Enxerto , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Custos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/métodos , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Prognóstico , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos
11.
Otolaryngol Head Neck Surg ; 154(1): 59-65, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26408563

RESUMO

OBJECTIVE: Chimeric anterolateral thigh free flaps are composed of multiple skin paddles or muscular components that allow for the reconstruction of complex 3-dimensional defects. We present our experience with the technique and applications for various head and neck defects. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary care center. SUBJECTS AND METHODS: Subjects include 24 consecutive patients undergoing reconstruction with a chimeric anterolateral thigh free flap by a single surgeon. Our algorithm for pharyngeal reconstruction with this technique is described. Data include demographics, indications, comorbidities, operative findings, and surgical outcomes. RESULTS: The most frequent defects were pharyngocutaneous (n = 12, 50%) and skull base (n = 6, 25%). The flap consisted of a double skin paddle in 11 cases (45.3%) and a skin paddle with an independent component of vastus lateralis muscle in 13 cases (54.7%). Revision surgery was required in 4 cases and was associated with malnutrition (P = .022). There were no total flap losses, but partial loss (distal skin paddle in all the cases) was observed in 3 patients and was related to severe congestive heart failure (P = .021) and malnutrition (P = .021). All except 1 patient who underwent pharyngeal reconstruction resumed oral diet and achieved alaryngeal speech. CONCLUSION: Chimeric anterolateral thigh free flaps represent an excellent option for reconstruction of complex head and neck defects. Modifications to the technique are proposed in patients at high risk of surgical complications.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Coxa da Perna/cirurgia , Resultado do Tratamento
12.
Oncotarget ; 7(6): 6576-92, 2016 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-26536665

RESUMO

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer. Pathologic activation of PI3K/mTOR pathway and elevated expression of c-Myc are frequently detected in MCC. Yet, there is no targeted therapy presently available for this lethal disease. Recently, MLN0128, a second-generation dual TORC1/2 inhibitor is shown to have therapeutic efficacy in preclinical studies. MLN0128 is currently in clinical trials as a potential therapy for advanced cancers. Here we characterize the therapeutic efficacy of MLN0128 in the preclinical setting of MCC and delineate downstream targets of mTORC1/2 in MCC cellular systems. MLN0128 significantly attenuates xenograft MCC tumor growth independent of Merkel cell polyomavirus. Moreover, MLN0128 markedly diminishes MCC cell proliferation and induces apoptosis. Further investigations indicate that senescence does not contribute to MLN0128-mediated repression of xenograft MCC tumor growth. Finally, we also observe robust antitumor effects of MLN0128 when administered as a dual therapy with JQ1, a bromodomain protein BRD4 inhibitor. These results suggest dual blockade of PI3K/mTOR pathway and c-Myc axis is effective in the control of MCC tumor growth. Our results demonstrate that MLN0128 is potent as monotherapy or as a member of combination therapy with JQ1 for advanced MCC.


Assuntos
Apoptose/efeitos dos fármacos , Benzoxazóis/farmacologia , Carcinoma de Célula de Merkel/patologia , Proliferação de Células/efeitos dos fármacos , Pirimidinas/farmacologia , Neoplasias Cutâneas/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Azepinas/farmacologia , Western Blotting , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/metabolismo , Senescência Celular , Sinergismo Farmacológico , Quimioterapia Combinada , Feminino , Humanos , Técnicas Imunoenzimáticas , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Triazóis/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Epigenetics ; 10(6): 460-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25941994

RESUMO

Pathologic c-Myc expression is frequently detected in human cancers, including Merkel cell carcinoma (MCC), an aggressive skin cancer with no cure for metastatic disease. Bromodomain protein 4 (BRD4) regulates gene transcription by binding to acetylated histone H3 lysine 27 (H3K27Ac) on the chromatin. Super-enhancers of transcription are identified by enrichment of H3K27Ac. BET inhibitor JQ1 disrupts BRD4 association with super-enhancers, downregulates proto-oncogenes, such as c-Myc, and displays antitumor activity in preclinical animal models of human cancers. Here we show that an enhancer proximal to the c-Myc promoter is enriched in H3K27Ac and associated with high occupancy of BRD4, and coincides with a putative c-Myc super-enhancer in MCC cells. This observation is mirrored in tumors from MCC patients. Importantly, depleted BRD4 occupancy at the putative c-Myc super-enhancer region by JQ1 correlates with decreased c-Myc expression. Thus, our study provides initial evidence that super-enhancers regulate c-Myc expression in MCC.


Assuntos
Carcinoma de Célula de Merkel/genética , Epigênese Genética/genética , Proteínas Nucleares/genética , Proteínas Proto-Oncogênicas c-myb/biossíntese , Neoplasias Cutâneas/genética , Fatores de Transcrição/genética , Acetilação/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Azepinas/administração & dosagem , Carcinoma de Célula de Merkel/tratamento farmacológico , Carcinoma de Célula de Merkel/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cromatina , Elementos Facilitadores Genéticos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Metástase Neoplásica , Proteínas Nucleares/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Proto-Oncogênicas c-myb/genética , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Fatores de Transcrição/metabolismo , Triazóis/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Otolaryngol Head Neck Surg ; 151(1): 81-6, 2014 07.
Artigo em Inglês | MEDLINE | ID: mdl-24690762

RESUMO

OBJECTIVE: The University HealthSystem Consortium (UHC) database collects discharge information on patients treated at academic health centers throughout the United States. We sought to use this database to identify outcome predictors for patients undergoing total laryngectomy. A secondary end point was to assess the validity of the UHC's predictive risk mortality model in this cohort of patients. STUDY DESIGN: Retrospective review. SETTING: Academic medical centers (tertiary referral centers) and their affiliate hospitals in the United States. SUBJECTS AND METHODS: Using the UHC discharge database, we retrieved and analyzed data for 4648 patients undergoing total laryngectomy who were discharged between October 2007 and January 2011 from all of the member institutions. Demographics, comorbidities, institutional data, and outcomes were retrieved. RESULTS: The length of stay and overall costs were significantly higher among female patients (P < .0001), while age was a predictor of intensive care unit stay (P = .014). The overall complication rate was higher among Asians (P = .019) and in patients with anemia and diabetes compared with other comorbidities. The average institutional case load was 1.92 cases/mo; we found an inverse correlation (R = -0.47) between the institutional case load and length of stay (P < .0001). The UHC admit mortality risk estimator was found to be an accurate predictor not only of mortality (P < .0002) but also of intensive care unit admission and complication rate (P < .0001). CONCLUSION: This study provides an overview of laryngectomy outcomes in a contemporary cohort of patients treated at academic health centers. UHC admit mortality risk is an excellent outcome predictor and a valuable tool for risk stratification in these patients.


Assuntos
Centros Médicos Acadêmicos , Bases de Dados Factuais , Laringectomia/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Centros Médicos Acadêmicos/estatística & dados numéricos , Adolescente , Adulto , Idoso , Comorbidade , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Estados Unidos/epidemiologia
15.
Thyroid ; 22(4): 347-55, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22280230

RESUMO

BACKGROUND: Ultrasound (US) of the central neck compartment (CNC) is considered of limited sensitivity for nodal spread in papillary thyroid cancer (PTC); elective neck dissection is commonly advocated even in the absence of sonographic abnormalities. We hypothesized that US is an accurate predictor for long-term disease-free survival, regardless of the use of elective central neck dissection in patients with PTC. METHODS: A retrospective chart review of 331 consecutive PTC patients treated with total thyroidectomy at M.D. Anderson Cancer Center between 1996 and 2003 was performed. Information retrieved included preoperative sonographic status of the CNC, surgical treatment of the neck, demographics, cancer staging, histopathological variables and use of adjuvant treatment. The endpoints for the study were nodal recurrence and survival. RESULTS: There were 112 males and 219 females with a median age of 44 years (range 11-87). The median follow-up time for the series was 71.5 months (range 12.7-148.7). There were 151 (45.6%) patients with a T1, 58 (17.5%) with a T2, 70 (21.1%) with a T3, and 52 (15.7%) with a T4. Preoperative sonographic abnormalities were present in the CNC in 79 (23.9%) patients. During the surveillance period, 11 (3.2%) patients recurred in the central neck, with an average time for recurrence of 22.8 months. Advanced T stage (T3/T4) and abnormal US were independent prognostic factors for recurrence in the central neck (p=0.013 and p=0.005 respectively). There were 119 (35%) patients with a sonographically negative central compartment who underwent elective central neck dissection; 85 of them (71.4%) were found to be histopathologically N(+) while 34 (28.6%) were pN0. There were no differences in overall survival (p=0.32), disease specific survival (DSS; p=0.49), and recurrence-free survival (p=0.32) between these two groups. Preoperative US of the CNC was an age-independent predictor for overall survival (p<0.001), DSS (p=0.0097), and disease-free survival (p=0.0005) on bivariate Cox regression. CONCLUSIONS: US of the central compartment is an age-independent predictor for survival and CNC recurrence-free survival in PTC. Prophylactic neck dissection of the central compartment does not improve long-term disease control, regardless of the histopathological status of the lymph nodes retrieved. Our findings emphasize the ability of US to clinically detect relevant nodal disease and support conservative management of the CNC in the absence of abnormal findings.


Assuntos
Pescoço/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina , Carcinoma , Carcinoma Papilar , Criança , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Humanos , Radioisótopos do Iodo/uso terapêutico , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Pescoço/patologia , Pescoço/cirurgia , Esvaziamento Cervical , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Análise de Regressão , Sobrevida , Análise de Sobrevida , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , Ultrassonografia , Adulto Jovem
16.
Int J Cancer ; 130(5): 1208-15, 2012 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-21484791

RESUMO

It is well accepted that near-infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3-5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7-9 mm) were irradiated with a 808-nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG-treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69-70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular-targeted ICG-NIR laser therapy appears to have potential for treating superficial tumors.


Assuntos
Adenocarcinoma/radioterapia , Verde de Indocianina/uso terapêutico , Raios Infravermelhos/uso terapêutico , Terapia a Laser/métodos , Neoplasias Mamárias Experimentais/radioterapia , Animais , Feminino , Verde de Indocianina/metabolismo , Injeções Intravenosas , Camundongos
17.
Arch Otolaryngol Head Neck Surg ; 137(2): 157-62, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21339402

RESUMO

OBJECTIVE: To evaluate the long-term outcomes and prognostic value of our sonographically based surgical approach to the lateral neck for recurrences in papillary thyroid cancer (PTC). DESIGN: Retrospective medical chart review. SETTING: Tertiary cancer institution. PATIENTS: The study population comprised 331 consecutive patients primarily treated for papillary thyroid carcinoma (PTC) at a tertiary cancer institution between 1996 and 2003. The lateral neck compartments were surgically addressed only in the presence of abnormalities on ultrasonography (US). MAIN OUTCOME MEASURES: Recurrence-free interval and overall, disease-specific, and recurrence-free survival. RESULTS: There were 112 male and 219 female patients, with a median age of 44.7 years (range, 11-87 years). The median follow-up time for the series was 77.9 months (range, 12.7-148.7 months). Preoperative US abnormalities were found in the right neck in 13.3%, in the left neck in 12.3%, and bilaterally in 11.2%; all of these patients underwent a lateral neck dissection at the time of the thyroidectomy. There were 11 recurrences in the series (0.3%), with a median time to presentation of 22.8 months (range, 6.0-55.3 months). Predictors of lateral neck disease-free interval were T stage and distant disease at presentation (P = .01 and P < .001, respectively) and the sonographic status of the ipsilateral and central neck (P = .001 and P < .001). The number of abnormal neck compartments in US correlated with the risk of regional failure (P = .01). The presence of US abnormalities in the lateral neck decreased the 10-year disease-specific survival from 98.3% to 66.9% (P < .001). CONCLUSIONS: Preoperative US is an excellent outcome predictor for lateral neck disease-free interval and for disease-specific survival in PTC. Sonographically based surgical approach provides excellent long-term regional control and validates current treatment guidelines.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Pescoço/diagnóstico por imagem , Cuidados Pré-Operatórios , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/mortalidade , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia/diagnóstico por imagem , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/mortalidade , Tireoidectomia , Ultrassonografia , Adulto Jovem
18.
Ann Surg Oncol ; 18(4): 1047-51, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21104031

RESUMO

BACKGROUND: We have developed a nomenclature system that succinctly specifies the locations of parathyroid adenomas in the neck. We report our experience using the system in a large, contemporary cohort of patients. METHODS: A prospective, endocrine surgery database at a single, tertiary care center was retrospectively analyzed. We reviewed the records of 271 patients operated on for sporadic primary hyperparathyroidism between January 2006 and May 2008 and analyzed the effect of adenoma location at operative intervention and outcome. RESULTS: Adenomatous gland locations were classified intraoperatively as: A (adherent to posterior thyroid capsule) in 12.5% of cases; B (tracheoesophageal groove) in 17.3%; C TE groove but (close to clavicle) in 13.7%; D (directly over the recurrent laryngeal nerve) in 12.2%; E (easy to identify, inferior thyroid pole) in 25.8%; F (fallen into thymus) in 7.4%; and G gauge (within thyroid gland) in 0.4%. More than one enlarged gland was present in 10.7% of patients and usually involved coexistence of enlarged types A and E glands. Type F glands were associated with a longer mean operative time (p = 0.0487) and type E glands with a higher rate of outpatient surgery (p = 0.0195). At 6 months from the surgery, 94.5% of the patients were normocalcemic. CONCLUSIONS: Our nomenclature system provides a simple way to describe the locations of parathyroid adenomas. Type E adenomas were associated with a higher rate of outpatient surgery and type F adenomas with a longer operative time. Biochemical cure rates were comparable for all locations of single adenomas.


Assuntos
Adenoma/cirurgia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
19.
Head Neck ; 32(12): 1674-80, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20848405

RESUMO

BACKGROUND: We describe a minimally invasive surgical technique, tracheostomaplasty, to overcome anatomical deformities of the stoma that preclude successful retention of a stoma button for hands free tracheoesophageal (TE) speech. METHODS: We conducted a retrospective analysis of 21 patients who underwent tracheostomaplasty after laryngectomy to accommodate an intraluminal valve attachment for hands-free TE speech. RESULTS: Sixteen men and 5 women (median age, 65 years; median follow-up, 27.7 months) underwent tracheostomaplasty; 6 patients developed a mild cellulitis that required therapy and 5 patients required a minor revision surgery. At last follow-up, 15 (71%) patients successfully achieved hands-free TE speech using an intraluminal stoma button. Three patients only retained the intraluminal device to facilitate digital occlusion. Tracheostomaplasty failed in 3 patients because of granulation tissue formation or stomal stenosis. CONCLUSIONS: Tracheostomaplasty is a successful technique to improve intraluminal retention of a stoma button for hands-free TE speech in laryngectomy patients.


Assuntos
Retalhos de Tecido Biológico , Voz Esofágica , Idoso , Idoso de 80 Anos ou mais , Fáscia/transplante , Feminino , Humanos , Laringectomia , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Voz Esofágica/instrumentação , Traqueostomia/efeitos adversos , Traqueostomia/métodos
20.
Cancer ; 116(14): 3408-16, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20564059

RESUMO

BACKGROUND: The objective of this study was to identify measurable parameters that provide quality data for assessing how well cancer care adheres to accepted treatment guidelines and is delivered to any given patient with oral tongue cancer. METHODS: A retrospective chart review included 116 patients treated for T1-T2/N0-N1 squamous cell carcinoma (SCC) of the oral tongue between 1998 and 2003. A set of quality measures considered critical for outcome included: 1) accurate TNM staging at presentation, 2) documentation of margin status, 3) appropriate referral for adjuvant radiation therapy, and 4) neck dissection for depth of invasion>4 mm. In addition, 26 clinical endpoints involving pretreatment assessment, staging, treatment, surveillance, and symptom control were analyzed. RESULTS: Patients comprised 73 men and 43 women (median age, 57 years). Forty-one (35.3%) patients presented with stage I disease, 61 (52.6%) with stage II, and 14 (12.1%) with stage III. The overall 5-year survival rate for all patients was 68.6%. There was a 90.5% compliance with TNM staging at presentation, 99.1% for documentation of margin status, 98.2% for adequate referral to radiation therapy, and 88.7% for appropriate neck dissection based on depth of invasion. Compliance with clinical endpoints was variable and ranged from 100% for endpoints related to radiation therapy to <40% for endpoints related to speech pathology and rehabilitation. CONCLUSIONS: Overall compliance with documenting the 4 parameters designated as quality measures for treatment of oral tongue SCC was acceptable, thus demonstrating that it is possible to use these data for measuring effective cancer care.


Assuntos
Fidelidade a Diretrizes , Indicadores de Qualidade em Assistência à Saúde , Neoplasias da Língua/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/normas , Estadiamento de Neoplasias/normas , Garantia da Qualidade dos Cuidados de Saúde , Radioterapia Adjuvante/normas , Resultado do Tratamento
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