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Squamoid eccrine ductal carcinoma is a rare infiltrative tumor with morphologic features intermediate between squamous cell carcinoma (SCC) and sweat gland carcinomas such as microcystic adnexal carcinoma. Although currently classified as a sweat gland carcinoma, it has been debated whether squamoid eccrine ductal carcinoma is better classified as a variant of SCC. Furthermore, therapeutic options for patients with advanced disease are lacking. Here, we describe clinicopathologic features of a cohort of 15 squamoid eccrine ductal carcinomas from 14 unique patients, with next generation sequencing DNA profiling for 12 cases. UV-signature mutations were the dominant signature in the majority of cases. TP53 mutations were the most highly recurrent specific gene alteration, followed by mutations in NOTCH genes. Recurrent mutations in driver oncogenes were not identified. By unsupervised comparison of global transcriptome profiles in squamoid eccrine ductal carcinoma (n=7) to SCC (n=10), porocarcinoma (n=4), and microcystic adnexal carcinoma (n=4), squamoid eccrine ductal carcinomas displayed an intermediate phenotype between SCC and sweat gland tumors. Squamoid eccrine ductal carcinoma displayed significant higher expression of 364 genes (including certain eccrine markers) and significant lower expression of 525 genes compared to other groups. Our findings support the classification of squamoid eccrine ductal carcinoma as a carcinoma with intermediate features between SCC and sweat gland carcinoma.
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BACKGROUND: Large full-thickness lip defects present a reconstructive challenge. OBJECTIVE: To describe the impact on clinical outcomes and institutional cost of the depressor anguli oris myocutaneous (DAOM) flap as an axial pattern transposition flap for reconstruction of large, full-thickness lip defects. METHODS: A multicenter retrospective cohort study of adults with large full-thickness lip defects who underwent DAOM flap reconstruction from 2011 to 2018 was conducted. DAOM flap anatomy and surgical technique were reviewed. The primary outcome of flap viability as well as additional clinical outcomes of postoperative complications and functional results were documented with follow-up ranging up to 11 years. Median length of stay and average institutional cost of care were analyzed. RESULTS: A total of 12 patients underwent DAOM flap reconstruction for large full-thickness lip defects. There was 100% flap survival with no episodes of reoperation or readmission. All patients reported maintenance of distinct oral commissures, wide oral opening and full gingivolabial sulcus, excellent oral competence, and intelligible speech. Mean case length was 144 ± 11.5 min with a mean length of stay of 1.6 ± 0.5 days and estimated mean institutional cost of $3766.67 ± $1167.06. CONCLUSIONS: The DAOM flap is an excellent reconstructive option for large full-thickness lip defects with strong functional results and limited donor site morbidity and institutional cost of care.
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Lábio , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Procedimentos de Cirurgia Plástica/economia , Retalho Miocutâneo/transplante , Lábio/cirurgia , Idoso , Adulto , Neoplasias Labiais/cirurgia , Complicações Pós-Operatórias , Tempo de Internação/estatística & dados numéricos , Sobrevivência de EnxertoRESUMO
BACKGROUND: Cranial nerve injury is an uncommon but significant complication of neck dissection. We examined the association between the use of intraoperative neuromuscular blockade and iatrogenic cranial nerve injury during neck dissection. METHODS: This was a single-center, retrospective, electronic health record review. Study inclusion criteria stipulated patients > 18 years who had ≥ 2 neck lymphatic levels dissected for malignancy under general anesthesia with a surgery date between 2008 - 2018. Use of neuromuscular blockade during neck dissection was the primary independent variable. This was defined as any use of rocuronium, cisatracurium, or vecuronium upon anesthesia induction without reversal with sugammadex prior to surgical incision. Univariate tests were used to compare variables between those patients with, and those without, iatrogenic cranial nerve injury. Multivariable logistic regression determined predictors of cranial nerve injury and was performed incorporating Firth's estimation given low prevalence of the primary outcome. RESULTS: Our cohort consisted of 925 distinct neck dissections performed in 897 patients. Neuromuscular blockade was used during 285 (30.8%) neck dissections. Fourteen instances (1.5% of surgical cases) of nerve injury were identified. On univariate logistic regression, use of neuromuscular blockade was not associated with iatrogenic cranial nerve injury (OR: 1.73, 95% CI: 0.62 - 4.86, p = 0.30). There remained no significant association on multivariable logistic regression controlling for patient age, sex, weight, ASA class, paralytic dose, history of diabetes, stroke, coronary artery disease, carotid atherosclerosis, myocardial infarction, and cardiac arrythmia (OR: 1.87, 95% CI: 0.63 - 5.51, p = 0.26). CONCLUSIONS: In this study, use of neuromuscular blockade intraoperatively during neck dissection was not associated with increased rates of iatrogenic cranial nerve injury. While this investigation provides early support for safe use of neuromuscular blockade during neck dissection, future investigation with greater power remains necessary.
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Anestésicos , Fármacos Neuromusculares não Despolarizantes , gama-Ciclodextrinas , Humanos , gama-Ciclodextrinas/farmacologia , Fármacos Neuromusculares não Despolarizantes/efeitos adversos , Estudos Retrospectivos , Sugammadex , Doença Iatrogênica , AndrostanóisRESUMO
OBJECTIVE: Compare full-thickness skin grafts versus split-thickness skin grafts in scalp reconstruction. STUDY DESIGN: Retrospective chart review of patients who underwent scalp reconstruction with skin grafts performed at a single institution from 2011 to 2016. METHODS: χ2 or Fisher exact tests were used to compare graft integration and complication rates. The effects of graft type, defect type, graft size, and patient comorbidities on the likelihood of graft success and complications were analyzed using multivariate logistic regression. RESULTS: A hundred and twenty-five full-thickness and 93 split-thickness grafts were performed in 200 patients, including 68 defects (31.2%) with exposed calvarium. Full-thickness grafts required fewer average reconstructions (P = 0.002). A 92.8% of full-thickness grafts had complete graft integration compared with 78.5% of split-thickness grafts (P = 0.002). This difference was more evident in defects with exposed calvarium (87.2% vs. 47.6%, P ≤ 0.001). Despite higher rates of minor debridement, full-thickness grafts had less postoperative bone exposure and wound breakdown than split-thickness grafts on intact pericranium and exposed calvarium defects. Preoperative radiation, immunosuppression, and increased graft sizes were significant predictors of graft outcomes. CONCLUSIONS: Skin grafts, especially full-thickness, provide a versatile, reliable, and simple approach for reconstructing medium to large scalp defects in the appropriate patient. Even on defects with bare calvarium, full-thickness grafts can succeed when a vascularized recipient bed is prepared. Defects with exposed bone, larger graft sizes, preoperative radiation, and immunosuppression may result in decreased graft take and increased complications. LEVEL OF EVIDENCE: 3b.
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Melanoma is one of the most aggressive skin cancers due to its potential to metastasize widely in the body. The risk of metastasis is increased with later detection and increased thickness of the primary lesion, thus early identification and surgical removal is critical for higher survival rates for patients. However, even with appropriate treatment, some patients will develop recurrence which may be difficult to identify until advanced or causing symptoms. Recent advances in liquid biopsy have proposed less-invasive alternatives for cancer diagnosis and monitoring using minimal/zero invasion at sample collection, and circulating tumor cells(CTCs) have been considered a promising blood-based surrogate marker of primary tumors. However, previous CTC technologies relying on epithelial-cell adhesion molecules have limited to epithelial cells, thus hampering use of CTCs for non-epithelial cancers such as melanoma. Here, we used the Melanoma-specific OncoBean platform(MelanoBean) conjugated with melanoma specific antibodies(MCAM and MCSP). The device was used in comprehensive studies for diagnosing melanoma and evaluating surgery efficacy based on change in the number and characteristics of CTCs and CTC-clusters pre- and post-surgical treatment. Our study demonstrated that melanoma patients(n=45) at all stages(I-IV) have a noticeable number of MCTCs as well as MCTC-clusters compared to healthy donors(n=9)(P=0.0011), and surgical treatment leads to a significant decrease in the number of CTCs(P<0.0001). The CTCs recovered from the device underwent molecular profiling for melanoma-associated genes expression using multiplexed qRT-PCR, demonstrating the ability to monitor molecular signature through treatment. The presented MelanoBean and the comprehensive approach will empower prognostic value of CTCs in melanoma in much larger cohort studies.
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OBJECTIVE: Recent randomized data suggest that completion lymph node dissection after a positive sentinel lymph node biopsy (SLNB) improves locoregional control but does not improve survival for melanoma patients. Locoregional recurrences of head and neck cutaneous melanoma (HNCM) may result in significant morbidity. A better understanding of morbidity is thus important to inform decisions about whether to pursue completion neck dissection (ND). STUDY DESIGN: Cross-sectional study. SETTING: Academic tertiary care hospital. METHODS: Clinical data were collected for patients with HNCM seen between 2016 and 2019 who were at least 1-year disease free. Each patient completed the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (SLANSS), Neck Dissection Impairment Index, and SF-36 (Short Form-36). Scores were compared by surgical treatment: wide local excision (WLE) only, SLNB, and ND. Univariate and multivariable regression was performed. RESULTS: Of 474 patients, 140 returned questionnaires (29.5% response rate; WLE, n = 49; SLNB, n = 76; ND, n = 15). No significant differences in SLANSS or Neck Dissection Impairment Index scores were found between the WLE and SLNB groups. SLANSS scores differed by 2 SD (P = .001) in the ND cohort, which had a 36% rate of neuropathy. Neck impairment was worse by 1 SD (P = .01) in the ND cohort. No differences were found in SF-36 domains. CONCLUSION: Neuropathy and neck impairment are components of morbidity after ND. These risks must be balanced with potential morbidity of locoregional recurrence in HNCM.
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Neoplasias de Cabeça e Pescoço/cirurgia , Excisão de Linfonodo , Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Qualidade de Vida , Neoplasias Cutâneas/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Metástase Linfática , Masculino , Esvaziamento Cervical , Biópsia de Linfonodo Sentinela , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm. STUDY DESIGN: Retrospective study. SETTING: Tertiary care hospital. METHODS: Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM). RESULTS: After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response (P = .012). CONCLUSION: These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.
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Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , Laringe , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Laríngeas/cirurgia , Laringe/patologia , Linfócitos do Interstício Tumoral , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
BACKGROUND: Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT. METHODS: A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12. RESULTS: Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007). CONCLUSION: GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT.
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Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Quimiorradioterapia/efeitos adversos , Estudos Transversais , Feminino , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Ombro , Carcinoma de Células Escamosas de Cabeça e Pescoço , SobreviventesRESUMO
PURPOSE: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma that can be divided into two classes: virus-positive (VP) MCC, associated with oncogenic Merkel cell polyomavirus (MCPyV); and virus-negative (VN) MCC, associated with photodamage. EXPERIMENTAL DESIGN: We classified 346 MCC tumors from 300 patients for MCPyV using a combination of IHC, ISH, and qPCR assays. In a subset of tumors, we profiled mutation status and expression of cancer-relevant genes. MCPyV and molecular profiling results were correlated with disease-specific outcomes. Potential prognostic biomarkers were further validated by IHC. RESULTS: A total of 177 tumors were classified as VP-MCC, 151 tumors were VN-MCC, and 17 tumors were indeterminate. MCPyV positivity in primary tumors was associated with longer disease-specific and recurrence-free survival in univariate analysis, and in multivariate analysis incorporating age, sex, immune status, and stage at presentation. Prioritized oncogene or tumor suppressor mutations were frequent in VN-MCC but rare in VP-MCC. TP53 mutation developed with recurrence in one VP-MCC case. Importantly, for the first time we find that VP-MCC and VN-MCC display distinct sets of prognostic molecular biomarkers. For VP-MCC, shorter survival was associated with decreased expression of immune markers including granzyme and IDO1. For VN-MCC, shorter survival correlated with high expression of several genes including UBE2C. CONCLUSIONS: MCPyV status is an independent prognostic factor for MCC. Features of the tumor genome, transcriptome, and microenvironment may modify prognosis in a manner specific to viral status. MCPyV status has clinicopathologic significance and allows for identification of additional prognostic subgroups.
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Biomarcadores Tumorais , Carcinoma de Célula de Merkel/etiologia , Carcinoma de Célula de Merkel/mortalidade , Poliomavírus das Células de Merkel , Infecções por Polyomavirus/complicações , Infecções por Polyomavirus/virologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Célula de Merkel/diagnóstico , Transformação Celular Viral , Variações do Número de Cópias de DNA , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Oncogenes , Prognóstico , Microambiente TumoralRESUMO
PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Biomarcadores , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Fluordesoxiglucose F18 , Humanos , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Prognóstico , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios XRESUMO
Melanoma is among the most aggressive cancers, and its rate of incidence continues to grow. Early detection of melanoma has been hampered due to the lack of promising markers for testing. Recent advances in liquid biopsy have proposed noninvasive alternatives for cancer diagnosis and monitoring. Circulating tumor cells (CTCs) and cancer-exosomes are gaining influence as promising biomarkers because of their cancer-associated molecular markers and signatures. However, technologies that offer the dual-isolation of CTCs and exosomes using a single sample have not been thoroughly developed. The dual-utilization OncoBean (DUO) device is conjugated with melanoma specific antibodies, MCAM and MCSP, enabling simultaneous CTC and exosome isolations. Using blood samples from patients, CTCs and exosomes are specifically isolated from a single sample and then undergo molecular profiling for comprehensive study. Melanoma patients have 0-17CTCs mL-1 and 299 µg exosomal protein mL-1 while healthy donors display fewer than 2CTCs and 75.6 µg of exosomes mL-1, respectively. It is also demonstrated that both markers express melanoma-associated genes using multiplex qRT-PCR to test for expression pattern of a 96 gene panel. The dual isolation and molecular characterization will allow for further research into melanoma to identify viable markers for disease progression and treatment efficacy.
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PURPOSE: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery. METHODS: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998-2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS). RESULTS: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04- < 0.001) and DSS (p = 0.04-0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04). CONCLUSION: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/cirurgia , Estudos Retrospectivos , Terapia de Salvação , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the long-term outcomes of sentinel lymph node biopsy (SLNB) for head and neck cutaneous melanoma (HNCM). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: Longitudinal review of a 356-patient cohort with HNCM undergoing SLNB from 1997 to 2007. RESULTS: Descriptive characteristics included the following: age, 53.5 ± 19 years (mean ± SD); sex, 26.8% female; median follow-up, 4.9 years; and Breslow depth, 2.52 ± 1.87 mm. Overall, 75 (21.1%) patients had a positive SLNB. Among patients undergoing completion lymph node dissection following positive SLNB, 20 (27.4%) had at least 1 additional positive nonsentinel lymph node. Eighteen patients with local control and negative SLNB developed regional disease, indicating a false omission rate of 6.4%, including 10 recurrences in previously unsampled basins. Ten-year overall survival (OS) and melanoma-specific survival (MSS) were significantly greater in the negative sentinel lymph node (SLN) cohort (OS, 61% [95% CI, 0.549-0.677]; MSS, 81.9% [95% CI, 0.769-0.873]) than the positive SLN cohort (OS, 31% [95% CI, 0.162-0.677]; MSS, 60.3% [95% CI, 0.464-0.785]) and positive SLN/positive nonsentinel lymph node cohort (OS, 8.4% [95% CI, 0.015-0.474]; MSS, 9.6% [95% CI, 0.017-0.536]). OS was significantly associated with SLN positivity (hazard ratio [HR], 2.39; P < .01), immunosuppression (HR, 2.37; P < .01), angiolymphatic invasion (HR, 1.91; P < .01), and ulceration (HR, 1.86; P < .01). SLN positivity (HR, 3.13; P < .01), angiolymphatic invasion (HR, 3.19; P < .01), and number of mitoses (P = .0002) were significantly associated with MSS. Immunosuppression (HR, 3.01; P < .01) and SLN status (HR, 2.84; P < .01) were associated with recurrence-free survival, and immunosuppression was the only factor significantly associated with regional recurrence (HR, 6.59; P < .01). CONCLUSIONS: Long-term follow up indicates that SLNB showcases durable accuracy, safety, and prognostic importance for cutaneous HNCM.
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Neoplasias de Cabeça e Pescoço/patologia , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/efeitos adversos , Neoplasias Cutâneas/mortalidade , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Characterize long-term cranial nerve (CN) outcomes following sentinel lymph node biopsy (SLNB) based management for head and neck cutaneous melanoma (HNCM). METHODS: Longitudinal review of HNCM patients undergoing SLNB from 1997-2007. RESULTS: Three hundred fifty-six patients were identified, with mean age 53.5 ± 19.0 years, mean Breslow depth 2.52 ± 1.87 mm, and 4.9 years median follow-up. One hundred five (29.4%) patients had SLNB mapping to the parotid basin. Eighteen patients had positive parotid SLNs and underwent immediate parotidectomy / immediate completion lymph node dissection (iCLND), with six possessing positive parotid non-sentinel lymph nodes (NSLNs). Fifty-two of 356 (14.6%) patients developed delayed regional recurrences, including 20 total intraparotid recurrences: five following false negative (FN) parotid SLNB, three following prior immediate superficial parotidectomy, two following iCLND without parotidectomy, and the remaining 12 parotid recurrences had negative extraparotid SLNBs. Parotid recurrences were multiple (4.9 mean recurrent nodes) and advanced (n = 4 extracapsular extension), and all required salvage dissection including parotidectomy. Immediate parotidectomy/iCLND led to no permanent CN injuries. Delayed regional HNCM macrometastasis precipitated 16 total permanent CN injuries in 13 patients: 10 CN VII, five CN XI, and one CN XII deficits. Fifty percent (n = 10) of parotid recurrences caused ≥1 permanent CN deficits. CONCLUSIONS: Regional HNCM macrometastases and salvage dissection confer marked CN injury risk, whereas early surgical intervention via SLNB ± iCLND ± immediate parotidectomy yielded no CN injuries. Further, superficial parotidectomy performed in parotid-mapping HNCM does not obviate delayed intraparotid recurrences, which increase risk of CN VII injury. Despite lack of a published disease-specific survival advantage in melanoma, early disease control in cervical and parotid basins is paramount to minimize CN complications. LEVEL OF EVIDENCE: 4 (retrospective case series) Laryngoscope, 130:1707-1714, 2020.
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Traumatismos dos Nervos Cranianos/etiologia , Nervos Cranianos/fisiopatologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Linfonodos/patologia , Melanoma/diagnóstico , Biópsia de Linfonodo Sentinela/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Traumatismos dos Nervos Cranianos/epidemiologia , Traumatismos dos Nervos Cranianos/fisiopatologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Metástase Linfática , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Pescoço , Recidiva Local de Neoplasia , Estudos Prospectivos , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/secundário , Fatores de Tempo , Estados Unidos/epidemiologia , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: To report our institutional experience, management, and outcomes of cutaneous periauricular squamous cell carcinoma (SCC). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center. SUBJECTS: Patients undergoing treatment of cutaneous periauricular SCC from 2000 to 2016. RESULTS: A total of 112 patients had a median follow-up of 24.5 months, a mean ± SD age of 75.7 ± 10.6 years, and a strong male predominance (93.8%). Site distribution shows 87 (77.7%) auricular, 26 (23.2%) preauricular, and 10 (8.8%) postauricular lesions. Of auricular lesions, tumors involved the tragus (n = 3, 3.4%), helix/antihelix (n = 47, 54.0%), conchal bowl (n = 31, 35.6%), external auditory canal (n = 18, 16.1%), and lobule (n = 3, 3.4%). Most patients presented at stage I (52.7%) versus stages II (28.6%), III (6.3%), and IV (12.5%). Patients were largely treated surgically with primary tumor resection ranging from wide local excision to lateral temporal bone resection (± parotidectomy and neck dissection), with 17.0% and 5.4% receiving adjuvant radiation and chemoradiation, respectively. Metastatic spread was seen to the parotid (25.9%) and neck (26.8%), with most common cervical spread to level II. Overall survival, disease-specific survival, and disease-free survival at 3 years were 62%, 89%, and 56%, respectively. Nodal disease was associated with worse disease-specific survival (P < .001) and disease-free survival (P = .042). Pre- and postauricular sites were associated with worse overall survival (P = .007) relative to auricular sites. CONCLUSION: Among cutaneous SCC, periauricular subsites pose treatment challenges related to surrounding anatomy and represent a unique tumor population. The reported propensity toward recurrence and patterns of metastasis may better guide treatment of aggressive tumors to include regional nodal dissection.
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Importance: Prior studies suggest that the use of facial nerve monitoring decreases the rate of immediate postoperative facial nerve weakness in parotid surgery, but published data are lacking on normative values for these parameters or cutoff values to prognosticate facial nerve outcomes. Objective: To identify intraoperative facial nerve monitoring parameters associated with postoperative weakness and to evaluate cutoff values for these parameters under which normal nerve function is more likely. Design, Setting, and Participants: This retrospective case series of 222 adult patients undergoing parotid surgery for benign disease performed with intraoperative nerve monitoring was conducted at an academic medical institution from September 13, 2004, to October 30, 2014. The data analysis was conducted from May 2018 to January 2019. Main Outcomes and Measures: The main outcome measure was facial nerve weakness. Receiver operating characteristic curves were generated to define optimal cut point to maximize the sensitivity and specificity of the stimulation threshold, mechanical events, and spasm events associated with facial nerve weakness. Results: Of 222 participants, 121 were women and 101 were men, with a mean (SD) age of 51 (16) years. The rate of temporary facial nerve paresis of any nerve branch was 45%, and the rate of permanent paralysis was 1.3%. The mean predissection threshold was 0.22 milliamperes (mA) (range, 0.1-0.6 mA) and the mean postdissection threshold was 0.24 mA (range, 0.08-1.0 mA). The average number of mechanical events was 9 (range, 0-66), and mean number of spontaneous spasm events was 1 (range, 0-12). Both the postdissection threshold (area under the curve [AUC], 0.69; 95% CI, 0.62-0.77) and the number of mechanical events (AUC, 0.58; 95% CI, 0.50-0.66) were associated with early postoperative facial nerve outcome. The number of spasm events was not associated with facial nerve outcome. The optimal cutoff value for the threshold was 0.25 mA, and the optimal cutoff for number of mechanical events was 8. If a threshold of greater than 0.25 mA was paired with more than 8 mechanical events, there was a 77% chance of postoperative nerve weakness. Conversely, if a threshold was 0.25 mA or less and there were 8 mechanical events or less, there was 69% chance of normal postoperative nerve function. No parameters were associated with permanent facial nerve injury. Conclusions and Relevance: Postdissection threshold and the number of mechanical events are associated with immediate postoperative facial nerve function. Accurate prediction of facial nerve function may provide anticipatory guidance to patients and may provide surgeons with intraoperative feedback allowing adjustment in operative techniques and perioperative management.
Assuntos
Eletromiografia/métodos , Traumatismos do Nervo Facial/prevenção & controle , Monitorização Intraoperatória/métodos , Procedimentos Neurocirúrgicos , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgia , Nervo Facial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Glândula Parótida/inervação , Estudos RetrospectivosRESUMO
AIM: Soy isoflavones have been suggested as epigenetic modulating agents with effects that could be important in carcinogenesis. Hypomethylation of LINE-1 has been associated with head and neck squamous cell carcinoma (HNSCC) development from oral premalignant lesions and with poor prognosis. To determine if neoadjuvant soy isoflavone supplementation could modulate LINE-1 methylation in HNSCC, we undertook a clinical trial. METHODS: Thirty-nine patients received 2-3 weeks of soy isoflavone supplements (300 mg/day) orally prior to surgery. Methylation of LINE-1, and 6 other genes was measured by pyrosequencing in biopsy, resection, and whole blood (WB) specimens. Changes in methylation were tested using paired t tests and ANOVA. Median follow up was 45 months. RESULTS: LINE-1 methylation increased significantly after soy isoflavone (P < 0.005). Amount of change correlated positively with days of isoflavone taken (P = 0.04). Similar changes were not seen in corresponding WB samples. No significant changes in tumor or blood methylation levels were seen in the other candidate genes. CONCLUSION: This is the first demonstration of in vivo increases in tissue-specific global methylation associated with soy isoflavone intake in patients with HNSCC. Prior associations of LINE-1 hypomethylation with genetic instability, carcinogenesis, and prognosis suggest that soy isoflavones maybe potential chemopreventive agents in HNSCC.
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Metilação de DNA/efeitos dos fármacos , Suplementos Nutricionais , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Isoflavonas/farmacologia , Elementos Nucleotídeos Longos e Dispersos/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Glycine maxRESUMO
BACKGROUND: Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined. METHODS: A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed. RESULTS: PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up). CONCLUSIONS: PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.
Assuntos
Procedimentos Cirúrgicos Eletivos/mortalidade , Neoplasias Laríngeas/cirurgia , Laringectomia/mortalidade , Excisão de Linfonodo/mortalidade , Linfonodos/cirurgia , Terapia de Salvação , Neoplasias da Traqueia/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Laríngeas/patologia , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Traqueia/patologiaRESUMO
BACKGROUND: The purpose of this study was to evaluate the AJCC eighth edition clinical staging system for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma and to further understand how clinical stage and smoking history affect oncologic outcomes. The purpose of this study was to present the understanding of how clinical stage and smoking history affect oncologic outcomes in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (SCC) is critical for selecting patients for treatment deintensification. METHODS: Kaplan-Meier and Cox regression were used to evaluate overall survival (OS), locoregional recurrence-free survival (LRFS), and distant recurrence-free survival (DRFS). Concordance statistics (C-indices) were used to compare discriminating ability. RESULTS: The OS and DRFS but not LRFS were significantly distributed using the American Joint Committee on Cancer (AJCC) seventh and eighth editions criteria. The C-indices for OS, LRFS, and DRFS were 0.57, 0.54, and 0.60, respectively, using the AJCC seventh edition, and 0.63, 0.53, and 0.65, respectively, using the AJCC eighth edition. On multivariate analysis, 1 + pack-year smoking history correlated with OS (hazard ratio [HR] 1.96; 95% confidence interval [CI] 1.2-3.1; P < .01) but not LRFS or DRFS. CONCLUSION: These results support implementation of the AJCC eighth edition for HPV-associated oropharyngeal SCC. Clinical stage may be more important than smoking history in selection for deintensification.