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1.
Laryngoscope ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32658339

RESUMO

OBJECTIVES/HYPOTHESIS: Use validated eye-tracking technology to objectively measure 1) the attentional distraction of facial contour defects after superficial and total parotidectomy and 2) changes in attentional distraction with abdominal dermal fat graft reconstruction. METHODS: Standardized frontal and oblique facial images of 16 patients who had undergone superficial or total parotidectomy with or without fat graft reconstruction; four normal controls were obtained. One hundred casual observers were recruited to view these images, and gaze data were collected using a Tobii Pro eye-tracking system. Gaze durations for predefined facial areas of interest were analyzed using mixed-effects linear regression to test study hypotheses. RESULTS: For frontal images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (92 milliseconds, 95% confidence interval [CI]: 48-138 milliseconds, P < .001). Fat grafting normalized the attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .414). For oblique images, total parotidectomy increased gaze to the operated parotid area compared to the contralateral nonoperated parotid area (658 milliseconds, 95% CI: 463-854 milliseconds, P < .001). Fat grafting normalized this attentional distraction, with no difference in gaze time on the operated parotid region compared to normal control faces (P = .504). In both views, superficial parotidectomy demonstrated no significant attentional distractions, with or without fat grafting. CONCLUSIONS: This eye-tracking study objectively demonstrates that total parotidectomy results in a facial contour deformity that is distracting to observers, whereas superficial parotidectomy does not. For total parotidectomy, this attentional distraction can be normalized with dermal fat graft reconstruction. LEVEL OF EVIDENCE: 3b Laryngoscope, 2020.

2.
Am J Otolaryngol ; 41(6): 102642, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32682193

RESUMO

PURPOSE: To compare recurrent pleomorphic adenoma tumor burden as detected on magnetic resonance and computerized tomography imaging with postoperative histopathology. MATERIALS AND METHODS: 44 patients were identified at a tertiary medical center between 2000 and 2015. Patients were included if they had viewable preoperative imaging and a postoperative diagnosis of recurrent pleomorphic adenoma. Primary outcomes were differences in the number and size of lesions detected on imaging and pathology. RESULTS: The size in greatest dimension between pathology and imaging was not significant on aggregate MRI + CT (p = 0.78), MRI (p = 0.41), or CT (p = 0.69). There were more lesions found on pathology compared to both aggregate MRI + CT (p = 0.003) and CT alone (p = 0.014). The number of lesions between MRI and pathology failed to reach significance (p = 0.06). On univariate analysis, the interval between imaging and pathology (recurrent surgery) did not significantly affect the number of lesions detected (p = 0.18). On multivariable analysis, CT as the primary imaging modality and >1 recurrence was independently associated with greater inaccuracy with respect to number of lesions detected (p = 0.006; p = 0.008). CONCLUSION: The size of the largest lesion on pathology can be accurately determined with imaging. Compared to MRI, CT scans significantly underpredict the number of lesions found on pathology. MRI should be prioritized unless contraindications exist. These findings will help guide imaging choice, preoperative planning, and patient counseling.

3.
Oral Oncol ; 111: 104894, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32712575

RESUMO

BACKGROUND: We investigated T cell clonality (TCC) and T cell fraction (TCF) in human papilloma virus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) progressors [cases] vs. non-progressors [controls]. METHODS: This nested case-control study included patients undergoing intent-to-cure surgery ± adjuvant therapy from 6/1/2007-10/3/2016. Patients experiencing local/regional/distant disease (progressors), and a consecutive sample of non-progressors were matched (2 controls: 1 case) on tumor subsite, T-stage and number of metastatic lymph nodes. We performed imunosequencing of the CDR3 regions of human TCRß chains. RESULTS: 34 progressors and 65 non-progressors were included. There was no statistically significant difference in baseline TCF (range: 0.039-1.084) and TCC (range: 0.007-0.240) (p > 0.05). Female sex was associated with higher TCF (p = 0.03), while extranodal extension (ENE) was associated with lower TCF (p = 0.01). There was a positive correlation between tumor size and clonality (R = 0.34, p < 0.01). The strongest predictor of progression-free survival (PFS) was TCF (HR 0.80, 95%CI 0.66-0.96, p = 0.02). The strongest predictors of cancer specific survival (CSS) were TCF (HR0.69, 95%CI 0.47-1.00, p < 0.05) and Adult Comorbidity Evaluation-27 (ACE-27) score (p < 0.05). Similarly, the strongest predictors of overall survival (OS) were TCF (HR 0.62, 95%CI 0.43-0.91, p = 0.01) and ACE-27 score (p = 0.03). On multivariable modeling, TCF ≥ 0.4 was independently associated with PFS (HR 0.34, 95%CI 0.14-0.85, p = 0.02) while an ACE-27 score of ≥ 2 independently predicted CSS (HR 3.85, 95%CI 1.07-13.85, p = 0.04) and OS (HR 3.51, 95%CI 1.10-11.20, p = 0.03). CONCLUSIONS: In patients with HPV(+)OPSCC, TCF was higher in female patients and those without ENE, suggesting differential immune responses. Lower TCF was significantly and independently associated with disease progression. Better ACE-27 scores appear to predict improved oncologic control.

4.
Oral Oncol ; 108: 104822, 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32504888

RESUMO

OBJECTIVE: Prognostic factors specific to surgically managed human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) are not fully understood. Medical co-morbidities may have an impact on survival after surgical treatment. We aimed to identify co-morbidities associated with distant metastases-free survival (DMFS) and cancer-specific survival (CSS) in HPV(+)OPSCCs. METHODS: This is a retrospective case series of HPV(+)OPSCC patients at a tertiary referral center from 2007 to 2016. All patients in the study underwent primary intent-to-cure transoral resection with concomitant neck dissection ± adjuvant radiation ± chemotherapy. Exclusion criteria included a history of previous head and neck cancer or distant metastases at diagnosis. Associations with DMFS and CSS were evaluated using univariable and multivariable Cox regression and summarized with hazard ratios (HRs). RESULTS: 406 patients were included in the cohort (100% HPV(+), 90% Male). All had tumors of the tonsil (62%) or base of tongue (38%). Median follow-up for the cohort was 4.0 years (IQR: 2.6-6.2). Higher tumor stage and a higher Adult Comorbidity Evaluation-27 score were significantly associated with worse DMFS and CSS (p < 0.02 for all). A history of diabetes mellitus (N = 36, 9%) was significantly associated with DMFS (HR 3.05 [95%CI 1.26-7.37], p = 0.014) and CSS (HR 4.82 [95%CI 1.84-12.61], p = 0.001). On multivariable analysis, after adjusting for tumor stage, diabetes remained significantly associated with worse DMFS (HR 2.58 [95%CI 1.06-6.26], p = 0.037). CONCLUSION: Diabetes mellitus may be associated with worse DMFS and CSS in surgically managed HPV(+)OPSCC.

5.
Laryngoscope ; 130(8): E469-E478, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32413165

RESUMO

OBJECTIVES: To describe pain experience and opioid use after major head and neck reconstructive surgery. STUDY DESIGN: Retrospective cohort study. METHODS: Patients undergoing major head and neck surgery with microvascular free tissue transfer (free flaps) at a tertiary academic center were included. Pain scores (0-10) and demographic and clinical data were ascertained from medical records. Discharge opioid prescriptions and refills obtained within 30 days were recorded. Patient characteristics were compared with pain scores using nonparametric rank-sum tests and with likelihood of refill using logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: The study population comprised 445 patients. Median age was 60 years (interquartile range 50-68). Most patients had cancer (N = 350, 78%). The majority of free flaps were fibula (N = 153, 34%) or radial forearm (N = 159, 36%). Older patients reported significantly lower pain scores, whereas patients with opioid tolerance, anxiety, current smokers, and those undergoing larger volume resections or boney free flaps reported significantly higher pain scores. One-quarter (N = 115, 26%) of patients obtained opioid refills. Patients aged ≥ 60 years had one-half the odds of obtaining a refill compared with patients aged < 60 years (adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.33-0.84), whereas surgical defect volume ≥ 100 cm3 (aOR = 1.92, 95% CI = 1.21-3.07) and higher pain score (aOR = 1.19, 95% CI = 1.07-1.32 per 1 point increase) increased the odds of refill. CONCLUSION: Continued opioid use after discharge is common among patients undergoing major head and neck reconstruction, particularly for younger patients and after more extensive surgery. Older patients reported lower pain intensity and were less likely to obtain opioid refills, highlighting the wisdom of judicious opioid use for this vulnerable population. LEVEL OF EVIDENCE: IV Laryngoscope, 130: E469-E478, 2020.

6.
Otolaryngol Head Neck Surg ; : 194599820915529, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32312161

RESUMO

OBJECTIVES: Clinical variables affecting anesthetic recovery following transoral robotic surgery (TORS) to resect oropharyngeal squamous cell carcinoma have not been described. We aimed to explore risk factors associated with prolonged postanesthesia recovery following TORS. STUDY DESIGN: Retrospective case-control study. SETTING: Tertiary referral center, January 2010 to November 2016. SUBJECTS AND METHODS: Patients included adults undergoing primary TORS ± neck dissection for oropharyngeal squamous cell carcinoma. Patients were categorized by phase I recovery time into the "goal" recovery group (75th percentile [lower 3 quartiles], n = 272) and the "prolonged" recovery group (n = 91). Univariate and multivariate logistic regression analyses were performed to assess the associations between clinical characteristics and prolonged phase I recovery. RESULTS: A total of 363 patients were included. Median (interquartile range) duration of postanesthesia recovery was 1.5 hours (1.0-2.0). Prolonged recovery was associated with isoflurane (odds ratio, 2.83 [95% CI, 1.56-5.14], P < .001), midazolam (2.77 [1.50-5.12], P = .001), and larger opioid doses (1.26 [1.01-1.58] per 10-mg intravenous morphine equivalents, P = .040) and inversely associated with multimodal antiemetic therapy (0.34 [0.15-0.78], P = .011). Prolonged cases had higher rates of postoperative nausea and vomiting (n = 43 [47.2%] vs 86 [31.6%], P = .008), respiratory depression (28 [30.8%] vs 12 [4.4%], P < .001), sedation (Richmond Agitation-Sedation Scale < -2; 26 [28.6%] vs 35 [12.9%], P = .001), severe pain (numeric rating score ≥7; 31 [34.4%] vs 45 [17.2%], P = .001), and longer hospital stays (4 vs 3 days, P < .001). CONCLUSIONS: Several anesthetic factors are associated with anesthesia recovery duration, which may be shortened by efforts to reduce postoperative sedation, severe pain, and nausea/vomiting. Shortened anesthesia recovery time may reduce hospital stay.

7.
Head Neck ; 42(8): 2077-2087, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32190942

RESUMO

BACKGROUND: The da Vinci single-port (SP) robot is a new instrument for transoral robotic surgery (TORS) in oropharyngeal cancers (OPSCCs). We describe one-year SP surgical outcomes and compare them to da Vinci Si outcomes. METHODS: Retrospective cohort study at a high-volume TORS center. Consecutive patients undergoing TORS SP procedures from 10/2018 to 09/2019 were included. SP OPSCC outcomes were compared to a historical cohort of Si OPSCC patients. t tests were used to compare continuous variables; χ2 or Wilcoxon rank-sum tests were used to compare nonparametric categorical variables. RESULTS: Seventy-eight patients underwent SP TORS. The bleed rate was 5.1%, mortality rate was 2.6%, and conversion rate was 0%. Compared to the Si cohort, OPSCC patients undergoing TORS SP procedures saw no significant differences in operative time or post-TORS bleeds (P > .05). CONCLUSIONS: The SP is a comparably safe surgical instrument. Overall learning curve for the SP was rapid among experienced TORS surgeons.

8.
Laryngoscope ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31909842

RESUMO

OBJECTIVES: To assess the outcomes of abdominal dermal-fat grafting following superficial and total parotidectomy. METHODS: A retrospective chart review of parotidectomy patients was performed. Patients were divided into four groups based on surgical extent and grafting status: superficial parotidectomy (SP), superficial parotidectomy with grafting (SPg), total parotidectomy (TP), and total parotidectomy with grafting (TPg). Complication rates and operative times were then compared between surgically matched groups (SP vs. SPg, TP vs. TPg). Complications included graft necrosis, gustatory sweating, first-bite syndrome, infection, hematoma, sialocele, and seroma. Data was analyzed via chi-square and two-sample t testing, logistic regression, and one-way analysis of variance. RESULTS: The cohort consisted of 330 patients: 106 SP (32.12%), 61 SPg (18.48%), 82 TP (24.85%), and 81 TPg (24.55%). No donor site complications occurred. TPg resulted in seven graft necroses (8.64%), and 22 reported gustatory sweating (27.20% vs. 10 TP patients (12.2%), P = 0.016); SPg resulted in two necroses (3.28%). There were no other statistically significant differences in complication rates. Graft recipients receiving adjuvant radiation were more likely to develop necrosis (odds ratio [OR] 4.60, 95% confidence interval [CI], 1.16-18.27, P = .0194). Patients who developed gustatory sweating were 8.38 years younger (95% CI 2.66-14.10, P = 0.002, follow-up time > 48 days). Grafting did not increase operative times (TP/TPg: mean = 275.91/263.65 minutes, standard error of the mean = 41.96/33.75, P = 0.822). CONCLUSION: An abdominal dermal-fat graft is an excellent reconstructive choice for a parotidectomy defect and is not associated with increased complication rates or prolonged operative time. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

9.
Laryngoscope ; 130(3): 622-627, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31077407

RESUMO

OBJECTIVES/HYPOTHESIS: Sinonasal mucosal melanoma (SNMM) is a rare malignant neoplasm. No study to date has analyzed the impact that nodal metastases and distant metastases at diagnosis have on overall survival (OS) and disease-specific survival (DSS). STUDY DESIGN: Retrospective database review. METHODS: The Surveillance, Epidemiology, and End Results database was queried for cases of SNMM. Descriptive statistics were used analyze patient demographic and clinicopathologic variables. The Kaplan-Meier model was used to analyze survival, and the Cox proportional hazards model was used for multivariate analysis. RESULTS: Three hundred twenty-eight cases of SNMM were identified. The most frequent sinonasal anatomic location was the nasal cavity in 279 (73.0%) patients, followed by the maxillary sinus in 60 (15.7%) patients. Regional nodal metastases at diagnosis occurred in 33 (8.6%) patients, whereas distant metastases at diagnosis occurred in 41 (10.7%) patients. Five-year OS was 22.7%, and 5-year DSS was 26.8%. The presence of positive nodes at diagnosis (OS P < .0001, DSS P < .0001), distant metastases at diagnosis (OS P = .0442, DSS P = .0442), primary tumor site (OS P < .0001, DSS P < .0001), and increasing age (OS P = .0012, DSS P = .0016) were found to be significant as negative predictors of OS and DSS. CONCLUSIONS: SNMM is a rare pathologic entity with a poor prognosis. The presence of nodal and distant metastases at diagnosis are negative prognostic factors in OS and DSS. These factors can be used in the development of new models of risk stratification and to inform treatment strategies and surveillance patterns. LEVEL OF EVIDENCE: NA Laryngoscope, 130:622-627, 2020.

10.
Thyroid ; 29(11): 1615-1622, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31595822

RESUMO

Background: Anaplastic thyroid cancer (ATC) has poor prognosis with median overall survival (OS) of ∼6 months. We previously reported high PD-1/PDL-1 staining in ATC, raising the possibility of the productive application of the immunotherapeutic pembrolizumab. However, having found pembrolizumab to anecdotally have limited single-agent activity in ATC, we sought to alternatively define whether pembrolizumab might synergistically combine with chemoradiotherapy as initial ATC therapy. Methods: An investigator-initiated therapeutic phase 2 trial of pembrolizumab, 200 mg intravenously (IV) every 3 weeks, combined with chemoradiotherapy (docetaxel/doxorubicin, 20 mg/m2 each IV weekly plus volumetric modulated arc therapy) was initiated as frontline therapy (with or without surgery) in ATC to assess efficacy and toxicities. Six-month OS was selected as the primary endpoint using a Simon's optimal design with interim analysis (targeting accrual of 25 patients; Cohort A: prior resection, Cohort B: no resection). Based on a prior patient cohort-treated similarly, but without pembrolizumab, the design was such that, if 6-month true survival is 75%, the probability of declaring the approach worthy of further pursuit would be 91%. Results: Three patients were enrolled, two with rapidly enlarging unresectable neck masses. Early tumor responses were favorable in all three, and all three satisfactorily completed: intended radiotherapy, preceding and radiotherapy-concurrent pembrolizumab, and concurrent chemoradiotherapy. However, all three patients died <6 months following therapy initiation-one from pulmonary metastases and two from otherwise unexpected fatal pulmonary complications occurring subsequent to chemoradiotherapy completion-prompting study closure. Conclusions: Although initially tolerated and effective in terms of locoregional disease control, disappointing survival outcomes compared with historical controls raise uncertainty that the piloted approach merits further pursuit in ATC.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31536129

RESUMO

Importance: Transoral endoscopic head and neck surgery now plays an important role in the multidisciplinary management of oropharyngeal carcinoma. Previous generations of robotic surgical systems used a multiport system with a rigid stereo-endoscope and 2 wristed instruments that facilitated transoral robotic surgery. Objective: To evaluate a new single-port robotic surgical system in head and neck surgery prospectively through concurrent nonrandomized clinical trials. Design, Setting, and Participants: Two prospective clinical trials were conducted from December 16, 2016, to December 26, 2017, to assess the safety, feasibility, and performance of a flexible single-port robotic surgical system in 4 institutions, including 3 in the United States and 1 in Hong Kong. A total of 47 patients with tumors of the oropharynx were enrolled and underwent surgery. All patients were classified as having American Society of Anesthesiologists class I to III status and Eastern Cooperative Oncology Group status 0 to 1. An initial cohort of 7 patients underwent staging and endoscopic procedures for benign disease. The remaining 40 patients all had malignant tumors of the oropharynx. Main Outcomes and Measures: Safety was measured by the incidence of device-related serious adverse events. Feasibility and performance were measured by the conversion rate from the use of the single-port robotic surgical system to either open surgery or the use of any other transoral technology required to complete the planned procedure. Secondary end points of swallowing function and surgical margins were also measured. Results: All 47 patients (8 women and 39 men; mean [SD] age, 61 [8] years) safely underwent transoral resection with the single-port robotic surgical system without conversion to open surgery, laser surgery, or multiport robotic surgery. There were no intraoperative complications or device-related serious adverse events. Mean (SD) estimated intraoperative blood loss per procedure was 15.4 (23.9) mL; no patients received a transfusion. Two patients underwent a planned tracheotomy owing to medical comorbidity (previous chemoradiotherapy; obesity and severe sleep apnea). Two patients (4%) had grade III or IV postoperative hemorrhage, requiring a return to the operating room; however, both patients had medical comorbidities requiring the use of antithrombotic medication. The incidence of positive margins for patients with oropharyngeal malignancy was 3% (1 of 40). Within 30 days, 45 patients (96%) were eating by mouth and without the need for a percutaneous endoscopic gastrostomy tube. Conclusions and Relevance: This study describes the results of phase 2 clinical testing of a next-generation, robotic surgical system using a single-port architecture. The use of the device appears to be feasible, safe, and effective for transoral robotic surgery of oropharyngeal tumors. Trial Registration: ClinicalTrials.gov identifiers: NCT03010813 and NCT03049280.

13.
Head Neck ; 41(11): 3933-3939, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31460691

RESUMO

BACKGROUND: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is rising, even in elderly patients. The outcomes of transoral surgery (TOS) in this population are not entirely known. METHODS: A retrospective review was performed at two institutions from October 2003 to September 2016 on patients 70 years or older with HPV-related OPSCC treated with TOS. RESULTS: A total of 75 patients were included with a mean age of 74 years (70-87 years). At a median follow-up of 35.7 months, 3-year overall survival was 81.5% and disease-specific survival was 94.3%. Advanced cT stage (odds ratio, 2.74; 95% confidence interval, 1.13-6.64) negatively impacted OS. Conjunctive consolidation was performed to create a staging system with patients older than 80 years, severe comorbidity, and cT3-4 having worse survival. CONCLUSIONS: Elderly patients with HPV-related OPSCC treated with TOS have excellent survival and therefore should not be excluded from such therapy based on age alone.

14.
Am J Otolaryngol ; 40(5): 729-734, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303455

RESUMO

OBJECTIVES: To review swallowing, airway and speech outcomes following transoral robotic surgery (TORS) ±â€¯adjuvant therapy for human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC). METHODS: Patients underwent TORS ± standard adjuvant therapy from 5/1/2007-5/31/2015. Clinical data were recorded and descriptive analysis was performed. RESULTS: 267 patients met criteria. All patients underwent surgery at Mayo, however, only 41/81 and 71/119 patients received RT and CRT at a Mayo Clinic site. A PEG was placed in 77 patients (3 prior to any treatment, 74 reactively during adjuvant therapy), with 3 PEG dependent and 3 partially PEG reliant at last follow-up. Tracheostomy was performed in 30 (11%) patients; 28 were decannulated. Swallow evaluations were completed for 20/81 undergoing RT and 50/119 undergoing CRT at a median of 3.8 and 7.6 months post-treatment, respectively. An unrestricted oral diet was reported by 5% following RT and 12% following CRT on the Functional Oral Intake Scale. HN-PSS normalcy of diet scores indicated a diet beyond soft chewable foods for 27% following RT and 46% following CRT. No restriction of place, food, or companion was reported for the HN-PSS for public eating in 13% after RT and 33% after CRT. Aspiration of thin liquid was present in 17% and 28% following RT and CRT, respectively. HN-PSS understandability of speech was "always understandable" in 60% and 63%, following RT and CRT, respectively. Hoarseness was reported in 56% and 45% following RT and CRT respectively. CONCLUSION: Long-term PEG and tracheostomy dependence in this cohort is low. However, these outcomes under-represent the decrement in patient speech and swallowing following TORS ± standard adjuvant therapy for HPV(+)OPSCC.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Neoplasias Orofaríngeas/cirurgia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Procedimentos Cirúrgicos Robóticos/métodos , Centros Médicos Acadêmicos , Adulto , Idoso , Institutos de Câncer , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Estudos de Coortes , Nutrição Enteral/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Boca , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Neoplasias Orofaríngeas/diagnóstico , Neoplasias Orofaríngeas/epidemiologia , Infecções por Papillomavirus/diagnóstico , Cuidados Pós-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Estatísticas não Paramétricas , Traqueostomia/métodos , Resultado do Tratamento
15.
J Clin Oncol ; 37(22): 1909-1918, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31163012

RESUMO

PURPOSE: The purpose of this study was to determine if dose de-escalation from 60 to 66 Gy to 30 to 36 Gy of adjuvant radiotherapy (RT) for selected patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma could maintain historical rates for disease control while reducing toxicity and preserving swallow function and quality of life (QOL). PATIENTS AND METHODS: MC1273 was a single-arm phase II trial testing an aggressive course of RT de-escalation after surgery. Eligibility criteria included patients with p16-positive oropharyngeal squamous cell carcinoma, smoking history of 10 pack-years or less, and negative margins. Cohort A (intermediate risk) received 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks along with 15 mg/m2 docetaxel once per week. Cohort B included patients with extranodal extension who received the same treatment plus a simultaneous integrated boost to nodal levels with extranodal extension to 36 Gy in 1.8-Gy fractions twice per day. The primary end point was locoregional tumor control at 2 years. Secondary end points included 2-year progression-free survival, overall survival, toxicity, swallow function, and patient-reported QOL. RESULTS: Accrual was from September 2013 to June 2016 (N = 80; cohort A, n = 37; cohort B, n = 43). Median follow-up was 36 months, with a minimum follow-up of 25 months. The 2-year locoregional tumor control rate was 96.2%, with progression-free survival of 91.1% and overall survival of 98.7%. Rates of grade 3 or worse toxicity at pre-RT and 1 and 2 years post-RT were 2.5%, 0%, and 0%. Swallowing function improved slightly between pre-RT and 12 months post-RT, with one patient requiring temporary feeding tube placement. CONCLUSION: Aggressive RT de-escalation resulted in locoregional tumor control rates comparable to historical controls, low toxicity, and little decrement in swallowing function or QOL.

16.
Ear Nose Throat J ; : 145561319849010, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064246
17.
Tetrahedron ; 75(16): 2357-2363, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-31133770

RESUMO

Engineered myoglobins were recently shown to be effective catalysts for abiological carbene and nitrene transfer reactions. Here, we investigated the impact of substituting the conserved heme-coordinating histidine residue with both proteinogenic (Cys, Ser, Tyr, Asp) and non-proteinogenic Lewis basic amino acids (3-(3'-pyridyl)-alanine, p-aminophenylalanine, and ß-(3-thienyl)-alanine), on the reactivity of this metalloprotein toward these abiotic transformations. These studies showed that mutation of the proximal histidine residue with both natural and non-natural amino acids result in stable myoglobin variants that can function as both carbene and nitrene transferases. In addition, substitution of the proximal histidine with an aspartate residue led to a myoglobin-based catalyst capable of promoting stereoselective olefin cyclopropanation under nonreducing conditions. Overall, these studies demonstrate that proximal ligand substitution provides a promising strategy to tune the reactivity of myoglobin-based carbene and nitrene transfer catalysts and provide a first, proof-of-principle demonstration of the viability of pyridine-, thiophene-, and aniline-based unnatural amino acids for metalloprotein engineering.

18.
ACS Catal ; 9(2): 1514-1524, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31134138

RESUMO

Recent advances in metalloprotein engineering have led to the development of a myoglobin-based catalyst, Mb(H64V,V68A), capable of promoting the cyclopropanation of vinylarenes with high efficiency and high diastereo- and enantioselectivity. Whereas many enzymes evolved in nature often exhibit catalytic proficiency and exquisite stereoselectivity, how these features are achieved for a non-natural reaction has remained unclear. In this work, the structural determinants responsible for chiral induction and high stereocontrol in Mb(H64V,V68A)-catalyzed cyclopropanation were investigated via a combination of crystallographic, computational (DFT), and structure-activity analyses. Our results show the importance of steric complementarity and non-covalent interactions involving first-sphere active site residues, heme-carbene, and the olefin substrate, in dictating the stereochemical outcome of the cyclopropanation reaction. High stereocontrol is achieved through two major mechanisms. First, by enforcing a specific conformation of the heme-bound carbene within the active site. Second, by controlling the geometry of attack of the olefin on the carbene via steric occlusion, attractive van der Waals forces and protein-mediated π-π interactions with the olefin substrate. These insights could be leveraged to expand the substrate scope of the myoglobin-based cyclopropanation catalyst toward non-activated olefins and to increase its cyclopropanation activity in the presence of a bulky α-diazo-ester. This work sheds first light into the origin of enzyme-catalyzed enantioselective cyclopropanation, furnishing a mechanistic framework for both understanding the reactivity of current systems and guiding the future development of biological catalysts for this class of synthetically important, abiotic transformations.

19.
Int J Dermatol ; 58(10): 1184-1190, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30968948

RESUMO

BACKGROUND: Previous wide local excision prior to sentinel lymph node biopsy (SLNB) may have the potential to disrupt lymphatic channels, thus incorrectly identifying the sentinel node. The purpose of this study was to investigate: (1) regional recurrence rates of prior wide local excision compared to other biopsy techniques and (2) survival outcomes in patients with melanoma of the head and neck. METHODS: Between the years 2000 and 2016, 391 cases were reviewed with a median follow-up time of 30 months in a large tertiary care center. Biopsy practices included shave, punch, wide local excision, and narrow margin excisional/Mohs, and associations with time to local or regional relapse and death from melanoma were evaluated. Main outcomes included identification of sentinel lymph nodes, overall survival, and melanoma-specific survival. RESULTS: Of the 391 patients, biopsy patterns were as follows: 77 (19%) unknown biopsy, 30 (8%) prior wide local excision (WLE), 105 (27%) narrow margin excisional biopsy, 69 (18%) punch biopsy, and 110 (28%) shave biopsy. SLNB was successfully identified in all 30 patients whom had a prior WLE. There were 50 regional recurrences in the neck and 27 local recurrences with the median (IQR) at 1.2 years and 1.0 years, respectively. Multivariable associations of type of prior biopsy, depth of invasion, and nodal status with time to regional recurrence, local recurrence, overall survival, and melanoma-specific survival were not significantly different. CONCLUSIONS: Sentinel lymph node biopsy for melanoma of the head and neck can be successfully performed in patients after previous wide local excision.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Melanoma/cirurgia , Cirurgia de Mohs/métodos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Cutâneas/cirurgia , Idoso , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Margens de Excisão , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Cirurgia de Mohs/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/prevenção & controle , Biópsia de Linfonodo Sentinela/métodos , Pele/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia
20.
Oral Oncol ; 87: 43-48, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30527242

RESUMO

OBJECTIVES: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger. MATERIALS AND METHODS: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts. RESULTS: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001). CONCLUSION: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults.


Assuntos
Metástase Linfática/patologia , Neoplasias Bucais/terapia , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Fatores Etários , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Boca/cirurgia , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto Jovem
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