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BACKGROUND: Patients with solid organ transplant (SOT) are at increased risk of developing aggressive cutaneous malignancies due to their immunosuppression, particularly cutaneous squamous cell carcinoma (cSCC). PURPOSE: There is limited data regarding SOT patients with locally advanced cSCC requiring radical surgery and microvascular free tissue transfer (MVFTT). Our objectives were to characterize outcomes in SOT patients and compare them with a non-SOT cohort. STUDY DESIGN: This is a retrospective cohort study of patients undergoing MVFTT for advanced cSCC of the head and neck between January 2016 and May 2020 at a tertiary referral center. Patients who underwent MVFTT as part of curative intent surgery for advanced cSCC during the study were considered for inclusion. Exclusion criteria included distant metastasis, palliative intent treatment, age less than 18 years, and lip primaries. PREDICTOR: The predictor variable was SOT status. A cohort of non-SOT patients was matched to the SOT cohort based on age, smoking status, tumor stage, and defect size. MAIN OUTCOME VARIABLES: The primary reconstructive outcome was the major surgical complications and secondary outcome measures included major medical complications and minor surgical complications. The primary oncologic outcome was overall survival and the secondary outcome was disease-specific survival. The primary predictor was transplant status. COVARIATES: Covariates included patient comorbidities, prior treatment, tumor stage, type of reconstruction, pathologic findings, and adjuvant therapy. ANALYSIS: Continuous and categorical variables were compared using Student's T test and Fisher's exact test. Survival was calculated using the Kaplan-Meier method and differences in survival between groups were calculated using the log-rank test. Statistical significance was set a priori at P ≤ .05. RESULTS: Fourteen SOT and 14 matched non-SOT patients met inclusion criteria. There was not a statistically significant difference in the rate of major surgical complications (7 vs 7%, P = .74) between the SOT and non-SOT cohorts. Rates of minor (21 vs 43%, P = .26) wound complications and medical complications (0 vs 14%, P = .24) were also similar between the SOT and non-SOT cohorts. Locoregional recurrences and distant metastasis were more common for SOT patients, though this was not statistically significant. Overall survival was significantly worse for SOT patients (21.7 vs 31.0 months, P = .04), though there was not a significant difference in disease-free survival (9.8 vs 31.0 months, P = .17). CONCLUSIONS AND RELEVANCE: MVFTT in the management of SOT patients with locally advanced head and neck cSCC demonstrates similar complication rates with non-SOT patients. While survival and oncologic outcomes are worse in the SOT cohort, aggressive surgical intervention with MVFTT can be performed with comparable complication rates to patients without a history of SOT.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Transplante de Órgãos , Neoplasias Cutâneas , Humanos , Adolescente , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias Cutâneas/patologia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia , Neoplasias de Cabeça e Pescoço/cirurgiaRESUMO
Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.
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Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Inibidor p16 de Quinase Dependente de Ciclina/análise , Humanos , Neoplasias Orofaríngeas/patologia , Papillomaviridae , Infecções por Papillomavirus/patologia , Medicina de Precisão , Prognóstico , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
PURPOSE: High-risk oropharyngeal squamous cell carcinoma (OPSCC) associated with tobacco exposure remains difficult to treat due to high rates of locoregional recurrence similar to oral cavity squamous cell carcinoma (OCSCC). Current NCCN guidelines allow for surgical management of this disease, but oncologic and functional data in the modern era remain scarce. We sought to compare and contrast oncologic and functional considerations for surgical management of OPSCC and OCSCC in a cohort of Veterans. MATERIALS AND METHODS: We conducted a retrospective review of patients treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2017 and 2020, treated using a homogenous, multi-modality algorithm. RESULTS: OPSCC tumors presented with a higher rate of perineural invasion (p < 0.05) and extranodal extension (p = 0.02) compared to OCSCC tumors. Compliance with NCCN guidelines for adjuvant treatment were lower for OPSCC patients primarily due to a higher rate of previous irradiation; re-irradiation could be delivered in 75% of patients when recommended by NCCN guidelines. Total glossectomy was accompanied by concomitant total laryngectomy in 100% of OPSCC patients and 0% of OCSCC. CONCLUSION: Surgical resection and free flap reconstruction of high-risk OPSCC generates oncologic outcomes comparable to OCSCC with comparable complication rates but a lower overall functional status. Reconstruction focused on rapid healing allows for high-rates of re-irradiation and minimal treatment delays. LEVEL OF EVIDENCE: level 4.
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Boca/cirurgia , Neoplasias Orofaríngeas/cirurgia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Saúde dos Veteranos , Veteranos , Idoso , Terapia Combinada , Feminino , Retalhos de Tecido Biológico , Glossectomia , Humanos , Laringectomia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/radioterapia , Guias de Prática Clínica como Assunto , Radioterapia Adjuvante , Estudos Retrospectivos , Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Resultado do TratamentoRESUMO
OBJECTIVE: To compare functional outcomes of total laryngectomy (TL) with microvascular free tissue transfer (MVFTT) reconstruction in the treatment of dysfunctional larynx (DL) versus salvage therapy for locally recurrent disease in patients with a history of laryngeal squamous cell carcinoma (SCC). METHODS: Retrospective review from a tertiary medical center between August 2015 and August 2022. RESULTS: Sixty-nine patients underwent TL with MVFTT following primary laryngeal radiation or chemoradiation; 15 (22%) patients underwent functional laryngectomy (FL) and 54 (78%) underwent a salvage laryngectomy (SL). There were no total flap failures. Four (6%) patients developed a pharyngocutaneous fistula; one (7%) FL patient and 3 (6%) in the SL cohort. There was no significant difference in average hospital length of stay (LOS) between the cohorts (8.6 ± 3.0 days vs. 12.8 ± 10.1 days, p = 0.12). All patients (100%) in the FL cohort achieved a total oral diet compared to 41 (76%) in the SL cohort (p = 0.03). Two (13%) and 10 (19%) patients developed pharyngoesophageal stenosis in the FL and SL cohorts, respectively (p = 1.0). Nine (60%) and 23 (43%) patients in the FL and SL cohorts underwent tracheoesophageal puncture (TEP) placement, with 89% and 91% achieving fluency, respectively (p = 0.23). CONCLUSION: Although the role of TL for the definitive treatment of laryngeal SCC has decreased over the past 30 years, organ-preservation protocols can impact speech, swallowing, and airway protection with life-threatening consequences. The use of elective FL with MVFTT for the treatment of DL results in similar or better functional outcomes compared to SL for recurrent disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:222-227, 2024.
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Neoplasias Laríngeas , Laringe , Humanos , Laringectomia/efeitos adversos , Laringectomia/métodos , Resultado do Tratamento , Neoplasias Laríngeas/cirurgia , Neoplasias Laríngeas/patologia , Estudos Retrospectivos , Laringe/cirurgia , Laringe/patologia , Terapia de Salvação/métodosRESUMO
OBJECTIVES: Implementing enhanced recovery after surgery (ERAS) protocols and decreasing length of stay (LOS) have become a priority for major surgeries, including microvascular free tissue transfer (MVFTT) reconstruction of the head and neck. We describe an ERAS protocol with the goal to further reduce length of stay beyond national medians. METHODS: Retrospective chart review between August 2016 and February 2023, including all patients who underwent MVFTT after oral cavity, skull base, salivary gland, and cutaneous ablative surgery. An ERAS protocol was implemented in March 2020. RESULTS: A total of 383 patients were included. Approximately 59.8% underwent oral cavity MVFTT, 34.5% cutaneous and lateral skull base, and 5.8% maxillary and anterior skull base. A total of 209 (54.7%) patients had surgery prior to implementation of the ERAS protocol and 174 (45.3%) after. Median LOS decreased from 9 days (interquartile interval [IQR] 8-11) to 6 (IQR 5-7.5, p < 0.0001) following oral cavity MVFTT. For cutaneous and lateral skull base reconstruction, median LOS decreased from 6 days (IQR 5-8) to 3 (IQR 3-7, p < 0.0001). For anterior skull base and sinonasal MVFTT, median LOS decreased from 8 (IQR 7-9) to 5 days (IQR 4.5-7, p = 0.0005). Rate of discharge to skilled nursing or subacute rehabilitation facilities decreased (24% before ERAS, 9.2% after, p < 0.0001). Thirty-day readmission rate was similar before and after implementation (10.5% vs. 10.3, p = 0.954). Discharge to facility was associated with readmission (OR 2.34, 95% CI 1.12-4.89, p = 0.024). CONCLUSION AND RELEVANCE: Implementation of the ERAS protocol was associated with decreased LOS. There was no increase in rate of readmission. LEVEL OF EVIDENCE: N/A Laryngoscope, 2024.
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PURPOSE: This study aims to evaluate the factors most associated with early and late complications following microvascular free tissue transfer (MVFTT) after mandibulectomy. METHODS: A retrospective review of patients undergoing MVFTT after segmental mandibulectomy from September 2016 to February 2021 was performed across a single academic institution. Surgical variables were collected, including the location of the resultant mandibular defect (anterior vs posterior) and flap type (osseous or non-osseous). The primary outcome variables included postoperative complications (early, <90 days; and late, >90 days) and the patients' functional status (return to oral intake). Descriptive statistics, chi-square test, Fischer's exact test, and 2-sample t tests were used to analyze differences among variables. RESULTS: We analyzed a cohort of 114 consecutive patients with mandibular defects, comprising 57 anterior and 57 posterior defects. Bony free flaps with hardware were used to reconstruct 98% of anterior defects compared to 58% of posterior defects (P < .001). All soft tissue only flaps did not utilize any hardware during the reconstruction. Anterior defects demonstrated more late complications requiring additional surgery (30% vs 9%, P = .04). A secondary analysis of posterior mandibular reconstructions compared soft tissue only flaps and bony free flaps with hardware and showed equivalent rates of early (12% vs 13%, P > .99) and late (9% vs 8%, P > .99) complications requiring additional surgery while demonstrating a similar return to full oral competence (55% vs 46%, P = .52) and recovery of a 100% oral diet (67% vs 54%, P = .53). CONCLUSION: Osseous free tissue transfer for segmental mandibular defects remains the gold standard in reconstruction. In our patient cohort, anterior mandibular defects are associated with greater late (>90 day) complications requiring additional surgery. Comparable outcomes may be achieved with soft tissue only versus osseous free flap reconstruction of posterior mandibular defects.
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Retalhos de Tecido Biológico , Osteotomia Mandibular , Reconstrução Mandibular , Complicações Pós-Operatórias , Humanos , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Osteotomia Mandibular/métodos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Reconstrução Mandibular/métodos , Adulto , Neoplasias Mandibulares/cirurgia , Mandíbula/cirurgia , Procedimentos de Cirurgia Plástica/métodosRESUMO
Objectives: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway. Methods: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days of surgery were regarded as having started PORT on time. The demographics, tumor characteristics, and rate of timely PORT for the two cohorts of patients were compared. Results: From 2018 to 2021, our rate of PORT initiation within 6 weeks of surgery was 12% (n = 57). In 2022, our rate of timely PORT was 88% (n = 16), p < 0.5. Patient demographics and characteristics were similar with the exception of marital status and use of free-flap reconstruction. The 2022 cohort was more likely to be single (p < 0.5), and all patients underwent free-flap reconstruction in 2022 (p < 0.05). Conclusion: Early referrals, frequent communication, and use of a secure registry were the key to the success found by our group despite the socioeconomic challenges of our underserved, safety-net hospital patient population. The changes made at our institution should serve as a template for other institutions seeking to improve the quality of care for their HNSCC patients.
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Plasmodium, the parasite which causes malaria in humans multiplies in the liver and then infects circulating erythrocytes. Thus, the role of the erythrocyte cell membrane in antimalarial drug activity and resistance has key importance. The effects of the antiplasmodial N(6)-(4-methoxybenzyl)quinazoline-2,4,6-triamine (M4), and its inclusion complex (M4/HPßCD) with 2-hydroxypropyl-ß-cyclodextrin (HPßCD) on human erythrocytes and on cell membrane molecular models are herein reported. This work evidences that M4/HPßCD interacts with red cells as follows: a) in scanning electron microscopy (SEM) studies on human erythrocytes induced shape changes at a 10µM concentration; b) in isolated unsealed human erythrocyte membranes (IUM) a concentration as low as 1µM induced sharp DPH fluorescence anisotropy decrease whereas increasing concentrations produced a monotonically decrease of DPH fluorescence lifetime at 37°C; c) X-ray diffraction studies showed that 200µM induced a complete structural perturbation of dimyristoylphosphatidylcholine (DMPC) bilayers whereas no significant effects were detected in dimyristoylphosphatidylethanolamine (DMPE) bilayers, classes of lipids present in the outer and inner monolayers of the human erythrocyte membrane, respectively; d) fluorescence spectroscopy data showed that increasing concentrations of the complex interacted with the deep hydrophobic core of DMPC large unilamellar vesicles (LUV) at 18°C. All these experiments are consistent with the insertion of M4/HPßCD in the outer monolayer of the human erythrocyte membrane; thus, it can be considered a promising and novel antimalarial agent.
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Antimaláricos/química , Membrana Eritrocítica/química , Modelos Moleculares , Quinazolinas/química , Antimaláricos/farmacologia , Dimiristoilfosfatidilcolina/química , Dimiristoilfosfatidilcolina/metabolismo , Relação Dose-Resposta a Droga , Membrana Eritrocítica/metabolismo , Membrana Eritrocítica/ultraestrutura , Humanos , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/metabolismo , Quinazolinas/farmacologiaRESUMO
Iodinated contrast media can rarely cause severe allergic reactions during nonvascular urologic imaging procedures. Alternatives like gadolinium-based contrast may help mitigate this risk in susceptible patients. A 66-year-old woman with a documented iodine allergy presented with an obstructing stone in the right ureter. To avoid the risk of an allergic reaction, the decision was made to use an alternative non-iodinated contrast agent for retrograde pyelography prior to ureteral stent placement. Gadobenate dimeglumine, an MRI contrast agent, was diluted 50:50 with saline and utilized successfully to provide adequate opacification for safe stent placement without adverse reaction. The patient underwent repeat pyelography with gadobenate dimeglumine one month later during ureteroscopy without complication. This case demonstrates that diluted gadobenate can serve as an effective alternative to iodinated contrast media in patients at high risk of reaction to iodine-containing agents. While severe reactions to iodinated contrast are uncommon in nonvascular urologic procedures, they can still occur even with premedication. Gadolinium-based agents have been reported to provide sufficient opacification for most urologic interventions, though inferior radiographically to iodinated contrast. Further study on gadolinium efficacy and safety in this setting is warranted. However the present case supports gadobenate dimeglumine as a viable option for retrograde pyelography when allergy risk precludes iodinated contrast use.
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Prostate cancer (PCa) identified incidentally (iPCa) after surgical treatment for symptomatic benign prostatic hyperplasia (BPH) causing lower urinary tract symptoms (LUTS) is considered low risk by the most current guidelines. Management protocols for iPCa are conservative and are identical to other prostate cancers classified as having favorable prognoses. The objectives of this paper are to discuss the incidence of iPCa stratified by BPH procedure, to highlight predictors of cancer progression, and to propose potential modifications to mainstream guidelines for the optimal management of iPCa. The correlation between the rate of iPCa detection and the method of BPH surgery is not clearly defined. Old age, small prostate volume, and high pre-operative prostate-specific antigen (PSA) are associated with an increased likelihood of detecting iPCa. PSA and tumor grade are strong predictors of cancer progression and can be used along with magnetic resonance imaging (MRI) and potential confirmatory biopsies to determine disease management. In instances that iPCa requires treatment, radical prostatectomy (RP), radiation therapy, and androgen deprivation therapy all have oncologic benefits but may be associated with increased risk after the BPH surgery. It is advised that patients with low to favorable intermediate-risk prostate cancer undergo post-operative PSA measurement and prostate MRI imaging before electing to choose between observation, surveillance without confirmatory biopsy, immediate confirmatory biopsy, or active treatment. Subdividing the binary T1a/b cancer staging into more categories with ranging percentages of malignant tissue would be a helpful first step in tailoring the management of iPCa.
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Objectives: We aimed to operationalize a head and neck microvascular free tissue transfer (MVFTT) program at a Veterans Affairs (VA) hospital with the emphasis on initiating radiotherapy within 6 weeks of surgery for cancer patients and minimizing readmissions. Study Design: Case series. Setting: Tertiary care VA hospital. Methods: A retrospective analysis was performed on consecutive head and neck MVFTT patients from May 1, 2017 and April 30, 2022. Demographics, patient and disease characteristics, per-operative data and postoperative outcomes were recorded from the electronic medical record. We sought to compare our rate of 30-day readmissions with those published in the literature. Results: One hundred and forty-one procedures were performed in the queried timeframe. Eighty-four percent (119) were performed after oncologic resections and 16% (22) were for nononcologic procedures. The rate of total flap loss was <1% and the rate of partial flap loss was 3.5%. For mucosal defects, the fistula rate was 2.3%. The rate of return to the OR for any reason within 30 days was 7.8%. The 30-day readmission rate was 6.4% while the rates reported in the literature range from 13% to 20%. One hundred and four patients required postoperative radiotherapy (PORT) and 76% started PORT within 42 days of surgery. Conclusion: Operationalizing a head and neck MVFTT program with a VA hospital is safe and allows for the successful delivery of multimodality treatment to cancer patients. These resources can be expanded for the care of head and neck cancer treatment sequelae, such as osteoradionecrosis, and other nononcologic patient needs.
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INTRODUCTION: The incidence of ocular injury associated with maxillofacial trauma remains poorly defined, with reported rates ranging from 0.8% to 92%. Our study aims to more accurately characterize ocular injuries associated with midface fractures. METHODS: We performed a retrospective review of 1677 patients from 2015 to 2020 with midface fractures at a Level I trauma center. Isolated nasal bone and frontal process of the maxilla fractures were excluded. Demographic information, mechanism of injury, need for surgery, and ophthalmologic findings were documented. Statistical analysis was conducted using SPSS. RESULTS: 773 patients between the ages of 15 and 92 were identified. Trauma most commonly resulted from assault (63.8%). The association between the mechanism of injury and ocular injury was statistically significant (p = 0.003), with 78.6% of gunshot wounds and 44.3% of assault patients having an ocular injury. The Ophthalmology service evaluated 62.6% of cases preoperatively. Minor ocular injury occurred in 36% of patients, including 46.1% of isolated orbital floor, and 28.2% of zygomaticomaxillary complex fractures. Major ocular injury occurred in 10.5% of patients. CONCLUSIONS: Over 10% of patients with midface fractures were found to have major ocular injuries. Ophthalmologic exams should be performed for all patients with midface fractures to guide clinical decision making and prevent further intraoperative ocular insults. LEVEL OF EVIDENCE: Level 4. This study represents a retrospective cohort study analyzing ocular injuries detected in patients presenting to a Level I trauma center with maxillofacial fractures between 2015 and 2020 Laryngoscope, 133:1624-1629, 2023.
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Traumatismos Oculares , Fraturas Maxilares , Traumatismos Maxilofaciais , Fraturas Orbitárias , Ferimentos por Arma de Fogo , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Ferimentos por Arma de Fogo/complicações , Ferimentos por Arma de Fogo/epidemiologia , Traumatismos Maxilofaciais/cirurgia , Traumatismos Oculares/complicações , Traumatismos Oculares/epidemiologia , Fraturas Maxilares/etiologia , Fraturas Maxilares/complicações , Fraturas Orbitárias/complicações , Fraturas Orbitárias/epidemiologiaRESUMO
Objective: Cisplatin forms the backbone of systemic chemotherapy treatment for oropharyngeal squamous cell carcinoma (OPSCC). The ideal cisplatin dosing regimen remains yet to be fully defined for achieving optimal efficacy and toxicity profiles in patients with comorbidity. Methods: We retrospectively reviewed oncologic and toxicity data for patients with OPSCC treated at the Michael E. DeBakey Veterans Affairs Medical Center between 2000 and 2020 who initiated curative intent, definitive chemo-radiation with one of three single agent regimens: high dose (HD) cisplatin, low dose (LD) cisplatin or cetuximab. Results: Patients with HPV-associated tumors and nonsmokers demonstrated improved overall and disease-free survival along with locoregional and distant metastatic control regardless of chemotherapy regimen. Regardless of regimen selection, patients which received a cumulative cisplatin dose ≥200 mg/m2 had a lower rate of distant metastasis. The HD regimen resulted in a greater fraction (75% vs. 50%) of patients receiving a cumulative cisplatin dose ≥200 mg/m2 and a comparable measured toxicity burden compared to the LD regimen. Conclusions: Both HD and LD cisplatin regimens can be safely delivered to a Veteran OPSCC patient population which should allow for straightforward application of conclusions drawn from completed and active clinical trials testing cisplatin regimens. Level of Evidence: 4.
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OBJECTIVES: Retrospective studies have shown that head and neck squamous cell carcinoma (HNSCC) patients taking metformin demonstrate superior survival compared to their counterparts. We sought to determine whether metformin combined with chemoradiation would improve HNSCC patient survival compared to historical controls. MATERIALS AND METHODS: We conducted a Phase I/II prospective, single arm clinical trial in patients with newly diagnosed HNSCC (NCT02949700). Patients received platinum-based chemoradiation in combination with orally dosed metformin at one of 2 doses- 850 mg BID or 1500 mg BID administered during radiation, with a 2-week lead-in phase. Toxicity, disease response and survival metrics were ascertained throughout the study period. RESULTS: A total of 25 patients were evaluable for toxicity and survival; 9 failed to reach the predetermined 70% compliance with the study drug. No dose limiting toxicities were identified in the Phase I component and there were no grade 4 adverse events likely related to metformin throughout the study. The primary outcome for the Phase II component was met with a response rate of 96%. Three-year overall survival was â¼70% in the per protocol p16 + cohort and 0% in the per protocol p16- cohort. Survival among participants with a ≥70% metformin compliance to <70% metformin compliance demonstrated a trend towards improvement in the ≥70% compliance cohort, though this did not reach significance. CONCLUSION: Metformin is well tolerated during concurrent chemoradiation for HNSCC. Its effectiveness as a chemo-radiosensitizer remains unclear and will require further study with randomized controlled clinical trials in this patient population.
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Neoplasias de Cabeça e Pescoço , Metformina , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Retrospectivos , Metformina/uso terapêutico , Estudos Prospectivos , Neoplasias de Cabeça e Pescoço/tratamento farmacológicoRESUMO
BACKGROUND AND OBJECTIVE: The literature lacks knowledge about information preferences and decision-making in young prostate cancer patients. This study provides insight into information sources consulted and factors dictating treatment decision-making in young prostate cancer patients. METHODS: Subjects were identified from pathology consult service of a National Center of Excellence. Questionnaires were mailed to 986 men, under 50 years of age, diagnosed with Gleason score 6 prostate cancer between 2001 and 2005. RESULTS: Four hundred ninety-three men responded. The most common primary therapies were surgery 397 (81.4%), radiation 52 (10.7%), and active surveillance (AS) 26 (5.3%). Participants with at least some college education (P = 0.003) or annual income >$100,000 (P = 0.003) were more likely to consult three or more doctors. Amongst all treatments, "doctor's recommendation" was the most influential information source, although relatively less important in the AS group. Internet was the second most frequent information source. Participants with higher education (P = 0.0003) and higher income (P = 0.002) considered sexual function more important while making a treatment choice. Only 2% of the men preferred a passive role in the decision-making. Informed decision-making was preferred more by patients who chose radiation and AS while shared decision-making was preferred more by surgery patients (P < 0.05). The majority (89%) of the respondents did not regret their decision. No difference in satisfaction levels was found between different treatment modalities. CONCLUSIONS: This study provides insight into information sources consulted, such as the greater internet use, and various factors dictating treatment decision-making in young prostate cancer patients. There was an overall very high satisfaction rate regardless of the therapy chosen.
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Adenocarcinoma/terapia , Tomada de Decisões , Próstata/patologia , Neoplasias da Próstata/terapia , Conduta Expectante , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Adulto , Fatores Etários , Humanos , Masculino , Homens , Pessoa de Meia-Idade , Gradação de Tumores , Participação do Paciente , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgiaRESUMO
PURPOSE: We compared cuff sites and assessed anatomical and manometric differences between the transscrotal and perineal approaches to artificial urinary sphincter placement in fresh male cadavers. MATERIALS AND METHODS: Artificial urinary sphincter implantation using perineal and transscrotal incisions was performed in 15 fresh male cadavers. The artificial urinary sphincter cuffs were placed as proximal as possible using each approach. After measuring urethral circumference at each cuff site, an appropriately sized cuff was placed at each location. The 61 to 70 cm H(2)O pressure reservoir and control pump were then connected to the cuffs. Retrograde leak point pressure was assessed sequentially across each cuff. The paired t test was used to compare urethral circumference and retrograde leak point pressure between the 2 approaches. RESULTS: Mean urethral circumference using the perineal and transscrotal approaches was 5.38 (range 3.2 to 7.5) and 3.81 cm (range 3 to 4.5), respectively (p <0.0001, 95% CI of difference 0.99-2.13). Mean retrograde leak point pressure using the perineal and transscrotal approaches was 90.1 and 64.9 cm H(2)O, respectively (p = 0.0002, 95% CI of difference 13.7-33.5). On visual inspection of cuff sites, the perineal approach was more proximal on the urethra than the transscrotal approach. CONCLUSIONS: While the transscrotal approach to artificial urinary sphincter placement has the advantage of technical ease, the anatomical and manometric findings of this cadaver study suggest that the perineal approach offers a more proximal cuff location, more robust urethral size and more effective urethral coaptation than the transscrotal approach.
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Implantação de Prótese/métodos , Esfíncter Urinário Artificial , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Cadáver , Humanos , Masculino , Manometria , Períneo/anatomia & histologia , Escroto/anatomia & histologiaRESUMO
BACKGROUND: Patients on chronic pharmacologic immunosuppressive therapy are at increased risk of wound infection and complications after surgery. There is a paucity of data examining perioperative complications after microvascular free tissue transfer (MVFTT) reconstruction of the head and neck in this patient population. METHODS: Retrospective cohort study performed at two tertiary referral centers between August 2016 and May 2020. RESULTS: Nine hundred and seventy-nine patients underwent MVFTT during the study period; of these 47 (5%) patients were taking chronic immunosuppressive medications. The most common indications for immunosuppression were solid organ transplant and autoimmune disease. Fourteen (30%) patients had surgical complications within 30 days of surgery: 8 (17%) wound dehiscences, 6 (12%) hematomas, and 2 (4%) surgical site infections. There was one total and one partial flap failure with a 30-day reoperation rate of 4%. CONCLUSIONS: MVFTT of the head and neck appears to be safe in patients on chronic pharmacologic immunosuppression.
Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Terapia de Imunossupressão/efeitos adversos , Pescoço/cirurgia , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos RetrospectivosRESUMO
Introduction Standardized reconstruction protocols for large open anterior skull base defects with dural resection are not well described. Here we report the outcomes and technique of a multilayered reconstructive algorithm utilizing local tissue, dural graft matrix, and microvascular free tissue transfer (MVFTT) for reconstruction of these deformities. Design This study is a retrospective review. Results Eleven patients (82% males) met inclusion criteria, with five (45%) having concurrent orbital exenteration and eight (73%) requiring maxillectomy. All patients required dural resection with or without intracranial tumor resection, with the average dural defect being 36.0 ± 25.9 cm 2 . Dural graft matrices and pericranial flaps were used for primary reconstruction of the dural defects, which were then reinforced with free fascia or muscle overlay by means of MVFTT. Eight (73%) patients underwent anterolateral thigh MVFTT, with the radial forearm, fibula, and vastus lateralis comprising the remainder. Average total surgical time of tumor resection and reconstruction was 14.9 ± 3.8 hours, with median length of hospitalization being 10 days (IQR: 9.5, 14). Continuous cerebrospinal fluid drainage through a lumber drain was utilized in 10 (91%) patients perioperatively, with an average length of indwelling drain of 5 days. Postoperative complications occurred in two (18%) patients who developed asymptomatic pneumocephalus that resolved with high-flow oxygen therapy. Conclusion A standardized multilayered closure technique of dural graft matrix, pericranial flap, and MVFTT overlay in the reconstruction of large open anterior craniofacial dural defects can assist the reconstructive team in approaching these complex deformities and may help prevent postoperative complications.