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1.
Am J Otolaryngol ; 43(2): 103316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34952416

RESUMO

BACKGROUND: Total laryngectomy (TL) with thyroidectomy can pose significant risks to parathyroid function, and variance in rates of post-operative hypocalcemia (POH) based on extent of thyroidectomy have not been previously reported. Our objective is to identify the rates of hypocalcemia and hypoparathyroidism in TL+/-thyroidectomy and compare this to matched thyroidectomy alone cohorts. METHODS: Multi-institutional retrospective chart review of patients treated surgically for laryngeal cancer with TL or benign/malignant thyroid disease with thyroidectomy at regional tertiary care centers in New Orleans and Baton Rouge, Louisiana from 2016 to 2019. Cases were evaluated for post-operative and post-discharge calcium and parathyroid hormone levels, post-operative and long-term calcium supplementation, and intraoperative parathyroid identification and management. RESULTS: 101 TL and 319 thyroidectomy patients' charts were reviewed. Regression analysis revealed increased odds of hypocalcemia and hypoparathyroidism in TL + TT versus TT alone (OR 10.7, OR 16.5, p < 0.001, respectively). TL + HT versus HT alone had increased odds of hypoparathyroidism (OR 1.6, p < 0.001). TL with any thyroidectomy compared to TL alone demonstrated both increased odds of hypocalcemia and hypoparathyroidism (OR 4.4 p = 0.009, and OR 4.5 p = 0.05). Odds of requiring long-term calcium supplementation were significantly increased with the addition of thyroidectomy across all groups. TL + TT was 8 times as likely (p = 0.002) and TL + HT was 5.3 times as likely (p = 0.001) to require long-term calcium supplementation compared to TL alone. CONCLUSIONS: Thyroidectomy combined with TL demonstrates marked increased risk of parathyroid dysfunction and resultant POH. Despite improved visualization of soft tissue anatomy with TL, risk of parathyroid injury in these settings requires special attention to extent of parathyroid dissection and potential devascularization to reduce long-term sequelae of hyperparathyroidism. Therefore, post-operative calcium monitoring after TL is necessary and should resemble the long-standing stringent protocols that already exist for monitoring in thyroidectomy populations.


Assuntos
Hipocalcemia , Assistência ao Convalescente , Cálcio , Humanos , Hipocalcemia/epidemiologia , Hipocalcemia/etiologia , Laringectomia/efeitos adversos , Hormônio Paratireóideo , Alta do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Tireoidectomia/métodos
2.
Vasc Med ; 24(4): 324-331, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30924412

RESUMO

Calf claudication is a significant cause of walking limitation for patients with peripheral artery disease (PAD). Ankle-foot orthoses (AFO) are leg devices that can reduce the physical demands on the calf muscles during ambulation. The purpose of this study was to determine the efficacy of AFO on walking ability in patients with PAD. This was an open-label, interventional trial including 15 patients with calf claudication who were fit with AFO. Patients completed graded treadmill testing, followed by 12 weeks of unstructured community-based walking using the AFO ad libitum. Comparison of peak walking time (PWT) at baseline versus 12 weeks was the primary outcome. A secondary outcome was claudication onset time (COT) assessed during graded treadmill tests. Change in walking ability of AFO group patients was also compared to outcomes from a historical PAD control group (n = 10) who received upfront advice to walk at home. Patients in the AFO group significantly improved their walking ability from baseline to 12 weeks (mean ± SD) (PWT: 7.8 ± 5.1 to 9.3 ± 5.4 min, p = 0.049; COT: 3.0 ± 2.3 to 4.8 ± 2.7 min, p = 0.01). Change in PWT for AFO group patients when tested without using the devices was not significantly greater compared to historical controls (+1.4 ± 2.4 vs +0.1 ± 2.6 min, p = 0.16) but it was for COT (+1.8 ± 2.5 vs -0.6 ± 2.2 min, p = 0.02). This study found that AFO used during community-based walking improved the primary outcome of PWT in patients with PAD. Further, using AFO delayed claudication onset, indicating patients may be able to increase their walking activity. Large-scale, randomized controlled trials are needed to further explore the use of AFO for PAD. ClinicalTrials.gov identifier: NCT02280200.


Assuntos
Terapia por Exercício/instrumentação , Tolerância ao Exercício , Órtoses do Pé , Claudicação Intermitente/terapia , Limitação da Mobilidade , Doença Arterial Periférica/terapia , Caminhada , Idoso , Desenho de Equipamento , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Minnesota , Medidas de Resultados Relatados pelo Paciente , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Teste de Caminhada
3.
Ann Plast Surg ; 82(1): 53-54, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30260839

RESUMO

Isolated lingual and lower face Raynaud phenomenon without primary Raynaud of the digits is a very rare condition associated with chemoradiation therapy (RT) in previous reports. The condition, which more commonly presents in patients with a history of Raynaud disease, is often self-limiting, but vasodilating agents and steroids have been suggested as possible treatment options. Spasmodic torticollis is a different, more common entity, also associated with history of RT or previous head and neck surgery. We present a rare case of a patient who developed Raynaud phenomenon of the lower face and tongue in the presence of spasmodic torticollis after mandibulectomy and free fibula reconstruction followed by RT to the oral cavity and neck. Possible causes, pathophysiologic mechanisms and treatment options are discussed. This is the first report of botulinum toxin treatment of isolated secondary Raynaud phenomenon of the lower face and tongue.


Assuntos
Toxinas Botulínicas/administração & dosagem , Neoplasias Mandibulares/cirurgia , Osteotomia Mandibular/efeitos adversos , Procedimentos de Cirurgia Plástica/efeitos adversos , Doença de Raynaud/tratamento farmacológico , Torcicolo/tratamento farmacológico , Transplante Ósseo/efeitos adversos , Transplante Ósseo/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Fíbula/cirurgia , Seguimentos , Humanos , Masculino , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/radioterapia , Osteotomia Mandibular/métodos , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Radioterapia Adjuvante/efeitos adversos , Radioterapia Adjuvante/métodos , Doença de Raynaud/etiologia , Doença de Raynaud/fisiopatologia , Procedimentos de Cirurgia Plástica/métodos , Medição de Risco , Torcicolo/etiologia , Resultado do Tratamento
6.
Gait Posture ; 101: 14-20, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36696821

RESUMO

BACKGROUND: The effectiveness of community-based walking programs for patients with peripheral artery disease (PAD) can be limited by calf claudication during exercise. Recent evidence finds adding carbon fiber ankle foot orthoses (AFO) to a walking program can result in improvements in patient mobility and delay claudication onset when walking. RESEARCH QUESTION: How may carbon fiber AFO alter ankle walking mechanics and corresponding triceps surae muscle recruitment in a manner that could improve patient mobility? METHODS: In this repeated measures cohort study, fifteen patients with PAD were fit with bilateral AFO before completing self-paced gait analysis including electromyography. Patients were then given standard advice to walk at home using the devices for 12 weeks. Twelve patients completed follow-up testing. RESULTS: There were no significant interactions between main effects for any variable of interest (p ≥ 0.189). Further, there were no within-subjects main effects for testing time for self-selected gait speed or any of the kinetic or kinematic variables (p ≥ 0.435). There were significant main effects for AFO use with reductions in dorsi flexion (p < 0.001), plantar flexion at toe off (p < 0.001), ankle plantar flexor moment (p = 0.037), and ankle plantar flexor power (p < 0.001). Triceps surae recruitment did not change between AFO conditions (p > 0.05). SIGNIFICANCE: Adding carbon fiber AFO limits peak ankle motion and joint power during self-paced walking for people with PAD while maintaining their walking speed. These gait adaptions were maintained over our 12 weeks of walking practice time. A resulting decrease in plantar flexor power while maintaining gait speed may provide the mechanism by which AFO can delay claudication onset which are major barrier to PAD walking programs. Calf muscle recruitment was maintained when adding the AFO which suggests sufficient muscle exertion could exist to maintain muscle integrity with sustained AFO use.


Assuntos
Órtoses do Pé , Doença Arterial Periférica , Humanos , Tornozelo , Fibra de Carbono , Estudos de Coortes , Limitação da Mobilidade , Caminhada/fisiologia , Marcha/fisiologia , Articulação do Tornozelo/fisiologia , Doença Arterial Periférica/complicações , Claudicação Intermitente/terapia , Fenômenos Biomecânicos
7.
Int Arch Otorhinolaryngol ; 27(2): e329-e335, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125378

RESUMO

Introduction Head and neck lymphedema is an omnipresent morbidity related to head and neck cancer therapies. Studies on therapy for these patients in the acute postsurgical population have not been published to date. Objective To assess changes in the measurements of lymphedema in surgical head and neck cancer patients during the hospital stay with implementation of modified decongestive therapy (MDT). Methods Patients aged > 18 years undergoing neck dissection with or without primary-site resection or laryngectomy between 2016 and 2019 were included. Facial measurements were obtained prior to beginning MDT and again prior to discharge. A total facial composite measurement was calculated and used to assess change over time. Rates ≥ 2% of change were considered significant. Results A total of 38 patients were included (subsites: larynx = 27; thyroid = 4; oral cavity = 3; and neck = 4). The mean number of days between surgery and the start of lymphedema therapy was 3.0 days. The mean number of days between measurements was 5.2 days. Reduction in the total composite score was observed in 37 (97%) patients, and 35 (92%) patients had a total composite reduction score > 2%. Tumor subsite and surgery type did not portend toward greater percent change, except for those patients treated with total laryngectomy, regional flap reconstruction, and neck dissection ( p = 0.02). Conclusion Acute postsurgical inpatient MDT was associated with reduced total composite measurements in patients after head and neck surgery. As the first published study on lymphedema therapy in this acute postsurgical period, further prospective case-control studies are warranted to explore further benefits of acute therapy.

8.
JAMA Otolaryngol Head Neck Surg ; 149(7): 636-642, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37289469

RESUMO

Importance: The assessment and management of surgical margins in stage I and II oral cavity squamous cell carcinoma is one of the most important perioperative aspects of oncologic care, with profound implications for patient outcomes and adjuvant therapy. Understanding and critically reviewing the existing data surrounding margins in this context is necessary to rigorously care for this challenging group of patients and minimize patient morbidity and mortality. Observations: This review discusses the data related to the definitions related to surgical margins, methods for assessment, specimen vs tumor bed margin evaluation, and re-resection of positive margins. The observations presented emphasize notable controversy within the field about margin assessment, with early data coalescing around several key aspects of management, although studies are limited by their design. Conclusions and Relevance: Stage I and II oral cavity cancer requires surgical resection with negative margins to obtain optimal oncologic outcomes, but controversy persists over margin assessment. Future studies with improved, well-controlled study designs are required to more definitively guide margin assessment and management.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Estados Unidos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Margens de Excisão , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Estudos Retrospectivos
9.
Blood ; 115(2): 326-30, 2010 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-19884644

RESUMO

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17)(q22;q21) involving the PML and RARA genes is associated with exposure to agents targeting topoisomerase II (topoII), particularly mitoxantrone and epirubicin. We previously have shown that mitoxantrone preferentially induces topoII-mediated DNA damage in a "hotspot region" within PML intron 6. To investigate mechanisms underlying epirubicin-associated t-APL, t(15;17) genomic breakpoints were characterized in 6 cases with prior breast cancer. Significant breakpoint clustering was observed in PML and RARA loci (P = .009 and P = .017, respectively), with PML breakpoints lying outside the mitoxantrone-associated hotspot region. Recurrent breakpoints identified in the PML and RARA loci in epirubicin-related t-APL were shown to be preferential sites of topoII-induced DNA damage, enhanced by epirubicin. Although site preferences for DNA damage differed between mitoxantrone and epirubicin, the observation that particular regions of the PML and RARA loci are susceptible to these agents may underlie their respective propensities to induce t-APL.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 17/genética , Epirubicina/efeitos adversos , Leucemia Promielocítica Aguda/genética , Segunda Neoplasia Primária/genética , Translocação Genética/efeitos dos fármacos , Adulto , Antibióticos Antineoplásicos/administração & dosagem , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Cromossomos Humanos Par 15/metabolismo , Cromossomos Humanos Par 17/metabolismo , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/genética , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Epirubicina/administração & dosagem , Feminino , Humanos , Íntrons/genética , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/metabolismo , Pessoa de Meia-Idade , Mitoxantrona/farmacologia , Segunda Neoplasia Primária/induzido quimicamente , Segunda Neoplasia Primária/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteína da Leucemia Promielocítica , Locos de Características Quantitativas , Receptores do Ácido Retinoico/genética , Receptores do Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Inibidores da Topoisomerase II , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
10.
Ann Vasc Surg ; 26(3): 344-52, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22285349

RESUMO

BACKGROUND: The purpose of this study was to evaluate the 10-year outcome of patients presenting with asymptomatic moderate carotid artery stenosis, and to determine which factors correlate with progression of disease to stroke or revascularization. METHODS: A retrospective review of all new patients presenting with asymptomatic moderate carotid artery stenosis from July 1998 to December 2001 was undertaken. Patients were consecutively identified and included by using duplex ultrasonography to identify moderate carotid disease. Variables were recorded for all patient encounters through June 2010. The primary end point was occurrence of ipsilateral cerebrovascular stroke or revascularization event (SORE). Statin therapy and angiotensin blockade (STAB) were categorized as follows: STAB(0)-medical treatment with neither statin therapy nor angiotensin blockade, STAB(1)-treatment with only one of the two, STAB(2)-treatment with both. An amortized cost model analyzed the cost of SORE-free survival. RESULTS: Over a 42-month period, 468 carotids in 366 patients with an average age of 69.0 ± 8.7 years were evaluated. Over a mean follow-up of 6.6 ± 2.7 years, SORE occurred in 150 (32.1%) carotid arteries. Hyperlipidemia was predictive of SORE (hazard ratio [HR]: 1.543, 95% confidence interval [CI]: 1.053-2.262, P = 0.03). Medical therapies protective against SORE were beta-blockade (HR: 0.612, 95% CI: 0.435-0.861, P < 0.05), STAB(1) (HR: 0.487, 95% CI: 0.336-0.706, P < 0.01), and STAB(2) (HR: 0.149, 95% CI: 0.089-0.248, P < 0.01). At 10 years, SORE-free survival in STAB(2) was 82.7% ± 4.6%, STAB(1) was 56.3% ± 5.0%, and STAB(0) was 29.3% ± 5.4% (P < 0.01). The cost per SORE-free year in STAB(2) was $1,695.40 ± $275.60, STAB(1) was $3,916.80 ± $605.44, and STAB(0) was $4,126.40 ± $427.23 (P < 0.01). CONCLUSION: These data demonstrate the clinical and financial advantage of using both statin therapy and angiotensin pathway blockage in patients with asymptomatic moderate carotid artery stenosis.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estenose das Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Idoso , Angioplastia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/economia , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/economia , Doenças Assintomáticas , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/economia , Estenose das Carótidas/mortalidade , Estenose das Carótidas/cirurgia , Análise Custo-Benefício , Progressão da Doença , Intervalo Livre de Doença , Custos de Medicamentos , Quimioterapia Combinada , Endarterectomia das Carótidas , Feminino , Custos de Cuidados de Saúde , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/economia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , North Carolina , Estudos Retrospectivos , Índice de Gravidade de Doença , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Dupla
11.
J Clin Virol Plus ; 2(2): 100067, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35262037

RESUMO

Accurate and rapid laboratory tests are essential for the prompt diagnosis of COVID-19, which is important to patients and infection control. The Xpert Xpress SARS-CoV-2 test is a real-time RT-PCR intended for the qualitative detection of nucleic acid from SARS-CoV-2 in upper respiratory specimens. In this study, we assessed the analytical performance characteristics of this rapid test for SARS-CoV-2 in 60 bronchoalveolar lavage (BAL) specimens. BAL is a specimen type that is not authorized under EUA for the Xpert Xpress SARS-CoV-2 test. The limit of detection of the Xpert Xpress SARS-CoV-2 test was 500 copies/ml. The overall agreement of the Xpert Xpress SARS-CoV-2 test was 100%. The Xpert Xpress SARS-CoV-2 test is sensitive and specific to aid in diagnosis of COVID-19 using bronchoalveolar lavage.

12.
Microbiol Insights ; 15: 11786361221087537, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35341107

RESUMO

The Delta SARS-CoV-2 variant is very infectious, and it is spreading quickly during this pandemic. In the study, we compared viral loads estimated by means of the Ct values emerging from RT-PCR swab tests in surging cases infected with the SARS-CoV-2 Delta variant in the fourth wave of COVID-19 with the three prior waves. The data comprised viral loads from positive cases detected within the UPMC health care system in Allegheny County, Pennsylvania. A total of 2059 upper airway samples were collected and tested for SARS-CoV-2 positive by RT-PCR during March 2020 to September 2021. We did not observe significant difference in viral load difference between the third (December 2020 to January 2021) and fourth (June 2021 to September 2021) waves; however, they had the higher viral load than the first (March 2020 to June 2020) and second waves (June 2020 to August 2020). We did find an age-related effect with the elderly presenting with lower viral loads, which was also seen in the earlier waves. However, the level of the viral loads in the fourth wave in the respect of the previous ones was not sufficiently increased to change our testing strategies by means of increased use of rapid antigen tests (RAT).

13.
Int Arch Otorhinolaryngol ; 26(4): e538-e547, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36405476

RESUMO

Introduction Patients with head and neck cancer (HNC) experience unique physical and psychosocial challenges that impact their health and quality of life. Early implementation of palliative care has been shown to improve various health care outcomes. Objective The aim of the present study was to evaluate the patterns of referral of patients with HNC to outpatient palliative care as they relate to utilization of resources and end-of-life discussions. Methods We performed a retrospective review of 245 patients with HNC referred to outpatient palliative care services at two Louisiana tertiary care centers from June 1, 2014, to October 1, 2019. The control group consisted of those that were referred but did not follow-up. Reasons for referral were obtained, and outcome measures such as emergency department (ED) visits, hospital readmissions, and advance care planning (ACP) documentation were assessed according to predictive variables. Results There were 177 patients in the treatment group and 68 in the control group. Patients were more likely to follow up to outpatient palliative care services if referred for pain management. Hospital system, prior inpatient palliative care, and number of outpatient visits were associated with an increased likelihood for ED visits and hospital readmissions. Those in the palliative care treatment group were also more likely to have ACP discussions. Conclusion Early implementation of outpatient palliative care among patients with HNC can initiate ACP discussions. However, there are discrepancies in referral reasons to palliative care and continued existing barriers to its effective utilization.

14.
Surg Endosc ; 25(5): 1553-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-20976478

RESUMO

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) should not cost more or less than traditional laparoscopic cholecystectomy (LC). METHODS: Retrospective cost data were collected from the accounting records of a single institution. A direct comparison of LC and SILC was conducted. Data on the SILC cases converted to LC were included. The total operating room (OR) cost (actual cost to the hospital for equipment, time, and personnel) and the total OR charges (total derived from the OR cost plus a margin to cover overhead costs beyond material costs) were examined. The total hospital charges (OR charges plus hospital charges accrued in the perioperative period) also were included. Descriptive statistics were used to analyze the data, with p values less than 0.05 considered statistically significant. RESULTS: Over a period of 19 months, 116 cases of minimally invasive cholecystectomy were evaluated. Of the 116 patients, 48 underwent LC during the first half of that period, and 68 patients underwent SILC during the second half of that period. Nine of the single-incision procedures were converted to traditional LC, for a 13% conversion rate. The groups were well matched from a demographics standpoint, with no significant differences in age, gender, body mass index (BMI), diagnoses, American Society of Anesthesiology (ASA) class, or payment. Comparison of all attempted SILCs, including those converted, with all LCs showed no significant difference in cost category totals. A significant difference among all cost variables was found when SILCs were compared with SILCs that required conversion to LC. A significant difference among the cost variables also was found when LCs were compared with converted SILCs. CONCLUSION: The cost for SILC did not differ significantly from that for LC when standard materials were used and the duration of the procedure was considered. Converted cases were significantly more expensive than completed SILC and LC cases.


Assuntos
Colecistectomia Laparoscópica/economia , Colecistectomia Laparoscópica/métodos , Preços Hospitalares , Custos Hospitalares , Humanos , Salas Cirúrgicas/economia
15.
Genes Chromosomes Cancer ; 49(8): 726-32, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20544846

RESUMO

We compared genomic breakpoints at the PML and RARA loci in 23 patients with therapy-related acute promyelocytic leukemia (t-APL) and 25 de novo APL cases.Eighteen of 23 t-APL cases received the topoisomerase II poison mitoxantrone for their primary disorder. DNA breaks were clustered in a previously reported 8 bp "hot spot" region of PML corresponding to a preferred site of mitoxantrone-induced DNA topoisomerase II-mediated cleavage in 39% of t-APL occurring in patients exposed to this agent and in none of the cases arising de novo (P = 0.007). As to RARA breakpoints, clustering in a 3' region of intron 2 (region B) was found in 65% of t-APL and 28% of de novo APL patients, respectively. Scan statistics revealed significant clustering of RARA breakpoints in region B in t-APL cases (P = 0.001) as compared to de novo APL (P = 1). Furthermore, approximately 300 bp downstream of RARA region B contained a sequence highly homologous to a topoisomerase II consensus sequence. Biased distribution of DNA breakpoints at both PML and RARA loci suggest the existence of different pathogenetic mechanisms in t-APL as compared with de novo APL.


Assuntos
Cromossomos Humanos Par 15/genética , Cromossomos Humanos Par 17/genética , DNA de Neoplasias/genética , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Proteínas Nucleares/genética , Receptores do Ácido Retinoico/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Antineoplásicos/uso terapêutico , Pontos de Quebra do Cromossomo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Proteína da Leucemia Promielocítica , RNA Mensageiro/genética , Receptor alfa de Ácido Retinoico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Translocação Genética , Adulto Jovem
16.
Head Neck ; 43(5): 1509-1520, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33417293

RESUMO

BACKGROUND: Immunotherapy agents are used to treat advanced head and neck lesions. We aim to elucidate relationship between immunotherapy and surgical wound complications. METHODS: Retrospective multi-institutional case series evaluating patients undergoing ablative and flap reconstructive surgery and immunotherapy treatment. MAIN OUTCOME: wound complications. RESULTS: Eight-two (62%) patients received preoperative therapy, 89 (67%) postoperative, and 33 (25%) in both settings. Forty-one (31%) patients had recipient site complications, 12 (9%) had donor site. Nineteen (14%) had major recipient site complications, 22 (17%) had minor. There was no statistically significant difference in complications based on patient or tumor-specific variables. Preoperative therapy alone demonstrated increased major complications (odds ratio [OR] 3.7, p = 0.04), and trend to more donor site complications (OR 7.4, p = 0.06), however treatment in both preoperative and postoperative therapy was not. CONCLUSIONS: Preoperative immunotherapy may be associated with increased wound complications. Controlled studies are necessary to delineate this association and potential risks of therapy.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Neoplasias de Cabeça e Pescoço/cirurgia , Humanos , Imunoterapia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
17.
Blood ; 112(8): 3383-90, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18650449

RESUMO

Therapy-related acute promyelocytic leukemia (t-APL) with t(15;17) translocation is a well-recognized complication of cancer treatment with agents targeting topoisomerase II. However, cases are emerging after mitoxantrone therapy for multiple sclerosis (MS). Analysis of 12 cases of mitoxantrone-related t-APL in MS patients revealed an altered distribution of chromosome 15 breakpoints versus de novo APL, biased toward disruption within PML intron 6 (11 of 12, 92% vs 622 of 1022, 61%: P = .035). Despite this intron spanning approximately 1 kb, breakpoints in 5 mitoxantrone-treated patients fell within an 8-bp region (1482-9) corresponding to the "hotspot" previously reported in t-APL, complicating mitoxantrone-containing breast cancer therapy. Another shared breakpoint was identified within the approximately 17-kb RARA intron 2 involving 2 t-APL cases arising after mitoxantrone treatment for MS and breast cancer, respectively. Analysis of PML and RARA genomic breakpoints in functional assays in 4 cases, including the shared RARA intron 2 breakpoint at 14 446-49, confirmed each to be preferential sites of topoisomerase IIalpha-mediated DNA cleavage in the presence of mitoxantrone. This study further supports the presence of preferential sites of DNA damage induced by mitoxantrone in PML and RARA genes that may underlie the propensity to develop this subtype of leukemia after exposure to this agent.


Assuntos
Cromossomos Humanos Par 15 , Cromossomos Humanos Par 17 , Leucemia Promielocítica Aguda/induzido quimicamente , Leucemia Promielocítica Aguda/genética , Esclerose Múltipla/terapia , Translocação Genética , Adulto , Antígenos de Neoplasias/metabolismo , DNA/química , DNA Topoisomerases Tipo II/metabolismo , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Mitoxantrona/efeitos adversos , Mitoxantrona/farmacologia , Modelos Genéticos
18.
Proc Natl Acad Sci U S A ; 104(47): 18694-9, 2007 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-18000064

RESUMO

Leukemia-associated chimeric oncoproteins often act as transcriptional repressors, targeting promoters of master genes involved in hematopoiesis. We show that CRABPI (encoding cellular retinoic acid binding protein I) is a target of PLZF, which is fused to RARalpha by the t(11;17)(q23;q21) translocation associated with retinoic acid (RA)-resistant acute promyelocytic leukemia (APL). PLZF represses the CRABPI locus through propagation of chromatin condensation from a remote intronic binding element culminating in silencing of the promoter. Although the canonical, PLZF-RARalpha oncoprotein has no impact on PLZF-mediated repression, the reciprocal translocation product RARalpha-PLZF binds to this remote binding site, recruiting p300, inducing promoter hypomethylation and CRABPI gene up-regulation. In line with these observations, RA-resistant murine PLZF/RARalpha+RARalpha/PLZF APL blasts express much higher levels of CRABPI than standard RA-sensitive PML/RARalpha APL. RARalpha-PLZF confers RA resistance to a retinoid-sensitive acute myeloid leukemia (AML) cell line in a CRABPI-dependent fashion. This study supports an active role for PLZF and RARalpha-PLZF in leukemogenesis, identifies up-regulation of CRABPI as a mechanism contributing to retinoid resistance, and reveals the ability of the reciprocal fusion gene products to mediate distinct epigenetic effects contributing to the leukemic phenotype.


Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 17/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/metabolismo , Receptores do Ácido Retinoico/metabolismo , Sequência de Bases , Sítios de Ligação , Linhagem Celular , Cromatina/genética , Metilação de DNA , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Leucemia Promielocítica Aguda/patologia , Dados de Sequência Molecular , Proteína com Dedos de Zinco da Leucemia Promielocítica , Receptores do Ácido Retinoico/genética , Receptor alfa de Ácido Retinoico , Retinoides/farmacologia , Regulação para Cima
19.
Genes Chromosomes Cancer ; 48(3): 213-21, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19023877

RESUMO

The translocation t(16;21) involving RUNX1 (AML1) and resulting in the RUNX1-CBFA2T3 fusion is a rare but recurrent abnormality mostly found in therapy-related acute myeloid leukemia (t-AML) associated with agents targeting topoisomerase II (topo II). We characterized, at the genomic level, the t(16;21) translocation in a patient who developed t-AML after treatment of multiple sclerosis with mitoxantrone (MTZ). Long template nested PCR of genomic DNA followed by direct sequencing enabled the localization of RUNX1 and CBFA2T3 (ETO2) breakpoints in introns 5 and 3, respectively. Sequencing of the cDNA with specific primers showed the presence of the expected RUNX1-CBFA2T3 fusion transcript in leukemic cells. The RUNX1 intron 5 breakpoint was located at nucleotide position 24,785. This region contained an ATGCCCCAG nucleotide sequence showing approximately 90% homology to a "hotspot" DNA region ATGCCCTAG present in intron 6 of PML previously identified in therapy-related acute promyelocytic leukemia cases arising following treatment with MTZ. This study suggests a wider distribution in the human genome, and particularly at genes involved in chromosome translocations observed in t-AML, of DNA regions (hotspot) targeted by specific topo II drugs.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Mitoxantrona/efeitos adversos , Translocação Genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Análise Citogenética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mitoxantrona/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Análise de Sequência de DNA , Inibidores da Topoisomerase II , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
20.
Plast Reconstr Surg ; 144(5): 1171-1180, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31441806

RESUMO

BACKGROUND: When gastric pull-up is unsuccessful or unsuitable for total esophageal reconstruction, a supercharged pedicled jejunum can be used to reestablish gastrointestinal continuity. The authors reviewed their technique and outcomes of the supercharged pedicled jejunum for total esophageal reconstruction. METHODS: A retrospective review of a prospectively maintained database was performed of 100 patients who underwent supercharged pedicled jejunum for total esophageal reconstruction between 2000 and 2017 at the Texas Medical Center. Patient characteristics, technical details, and outcomes were analyzed. RESULTS: Mean patient age was 59.5 ± 11.4 years. Forty-two patients (42 percent) had surgical complications (18 percent at the recipient site, 13 percent at the donor site, and 11 percent at both). Medical complications occurred in 28 patients (28 percent). A major surgical complication occurred in 20 patients (20 percent). The average length of stay was 15 days (range, 6 to 152 days). At last follow-up, 20 patients (20 percent) had metastatic disease and six (6 percent) had local recurrence. Fifty-four patients (54 percent) died during the follow-up period. Of 79 patients with follow-up longer than 6 months, 68 (86 percent) tolerated a solid or soft oral diet, with a 16 percent tube feed-dependence rate. Overall survival at 1, 3, and 5 years was 78.8, 53.7, and 33.1 percent, respectively. The median survival time was 38.7 months. CONCLUSIONS: The authors present their experience with 100 supercharged pedicled jejunums for total esophageal reconstruction. Functional outcomes are comparable to, or better than, other salvage modalities. With careful multidisciplinary planning and meticulous, well-orchestrated surgical technique, swallowing function can be restored to provide quality of life in patients with few remaining surgical options.


Assuntos
Neoplasias Esofágicas/mortalidade , Esofagectomia/métodos , Jejuno/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Idoso , Bases de Dados Factuais , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Procedimentos de Cirurgia Plástica/mortalidade , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
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