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1.
J Surg Oncol ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32153030

RESUMO

BACKGROUND AND OBJECTIVES: The number of patients diagnosed with head and neck squamous cell carcinoma (HNSCC) at an advanced age has increased. The aim of this study is to evaluate the age at which disease-specific survival (DSS) significantly decreases in HNSCC. METHODS: We performed a retrospective study of 5469 patients with HNSCC treated at our center (1985-2016). External validation with 2082 oral squamous cell carcinomas from a collaborative institution from another continent was performed. RESULTS: We observed an orderly decrease in overall survival as age at diagnosis increased. There were no differences in DSS based on age for patients <80 years old (P = .623), while older patients had a significant decrease in DSS. These results were validated in the independent dataset. In a multivariable analysis performed in the test set, compared to patients <80 years old, patients between 80 to 85 had a 1.50 times higher risk of disease-specific death (95% confidence interval [CI]: 1.19-1.89; P = .001), and patients >85 had a 2.19 times higher risk (95% CI: 1.68-2.87; P < .001). CONCLUSIONS: DSS started to significantly decrease in HNSCC at 80 years old. These findings, validated in an independent cohort, indicate that chronological age on its own should not withhold curative treatment in the majority of patients with HNSCC.

2.
Nat Biomed Eng ; 4(3): 272-285, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32165735

RESUMO

For oral, oropharyngeal and oesophageal cancer, the early detection of tumours and of residual tumour after surgery are prognostic factors of recurrence rates and patient survival. Here, we report the validation, in animal models and a human, of the use of a previously described fluorescently labelled small-molecule inhibitor of the DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP1) for the detection of cancers of the oral cavity, pharynx and oesophagus. We show that the fluorescent contrast agent can be used to quantify the expression levels of PARP1 and to detect oral, oropharyngeal and oesophageal tumours in mice, pigs and fresh human biospecimens when delivered topically or intravenously. The fluorescent PARP1 inhibitor can also detect oral carcinoma in a patient when applied as a mouthwash, and discriminate between fresh biopsied samples of the oral tumour and the surgical resection margin with more than 95% sensitivity and specificity. The PARP1 inhibitor could serve as the basis of a rapid and sensitive assay for the early detection and for the surgical-margin assessment of epithelial cancers of the upper intestinal tract.

3.
Nucl Med Biol ; 84-85: 80-87, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-32135475

RESUMO

OBJECTIVES: The evaluation of disease extent and post-therapy surveillance of head and neck cancer using 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) PET is often complicated by physiological uptake in normal tissues of the head and neck region, especially after surgery or radiotherapy. However, irrespective of low positive predictive values, [18F]FDG PET remains the standard of care to stage the disease and monitor recurrences. Here, we report the preclinical use of a targeted poly (ADP-ribose) polymerase1 (PARP1) binding PET tracer, fluorine-18 labeled poly (ADP-ribose) polymerase1 inhibitor ([18F]PARPi), as a potential alternative with greater specificity. METHODS: Using an orthotopic xenograft mouse model injected with either FaDu or Cal 27 (human squamous cell carcinoma cell lines) we performed PET/CT scans with the 2 tracers and compared the results. Gamma counts and autoradiography were also assessed and correlated with histology. RESULTS: The average retained activity of [18F]PARPi across cell lines in tumor-bearing tongues was 0.9 ±â€¯0.3%ID/g, 4.1 times higher than in control (0.2 ±â€¯0.04%ID/g). Autoradiography and histology confirmed that the activity arose almost exclusively from the tumor areas, with a signal/normal tissue around a ratio of 42.9 ±â€¯21.4. In vivo, [18F]PARPi-PET allowed delineation of tumor from healthy tissue (p < .005), whereas [18F]FDG failed to do so (p = .209). CONCLUSIONS AND IMPLICATIONS FOR PATIENT CARE: We demonstrate that [18F]PARPi is more specific to tongue tumor tissue than [18F]FDG. [18F]PARPi PET allows for the straightforward delineation of oral cancer in mouse models, suggesting that clinical translation could result in improved imaging of head and neck cancer when compared to [18F]FDG.

4.
Oral Oncol ; 104: 104607, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32208339

RESUMO

PURPOSE OF REVIEW: The objective of this article is to critically review the rationale for the changes in the staging of the oral cavity cancers. RECENT FINDINGS: After reviewing many recent studies about oral cancer and analyzing multi-institutional data for outcomes, the staging system was updated to include new knowledge of the disease and its biological behavior. SUMMARY: This article reviews the changes in the staging of oral cavity cancers published in the 8th edition of the AJCC/UICC TNM cancer staging manual and discusses future directions.

6.
Immunopharmacol Immunotoxicol ; 42(2): 128-137, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32070162

RESUMO

Objective: Asthma is a very common airway inflammatory disease for which the existing drug therapy options are insufficient. In this study, we explored the mechanisms underlying the anti-inflammatory potential of Sarsapogenin (SG) and its combination with Fluticasone (FC) in ovalbumin (OVA)-induced allergic asthma in mice.Methods: In a standard experimental model, asthma in mice was sensitized and challenged by OVA. The mice were treated with SG and SG + FC during OVA challenge. At the completion, lung weight, inflammatory cell count in bronchoalveolar lavage fluid (BALF), serum cytokines levels, immunoglobulin E (IgE) levels, lung nitrate/nitrite (NO) levels, and lung tissue oxidative stress biomarkers were determined. Histopathological evaluation of the lung tissue was also performed.Key findings: Treatment of mice with SG and SG + FC combination intensely diminished the trafficking of total and differential inflammatory cells count into BALF. SG and SG + FC administration significantly reduced the production of inflammatory cytokines, serum IgE levels and restoration of antioxidant stress markers. Histopathological analysis of lung samples effectually weakened bronchial inflammation and mucus production in the lung with a significant reduction in inflammation and mucus score.Conclusion: Our study results suggested that SG and SG + FC effectively reduced allergic airway inflammation via inhibiting pro-inflammatory cytokines, NO expressions and oxidative stress parameters. So, it could be used as a therapeutic potential agent for the treatment of asthma by decreasing its dose in combination with FC to avoid the chronic adverse effects of FC.

7.
Cancer ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32097509

RESUMO

BACKGROUND: Distant metastases (DMs) are the primary cause of treatment failure in patients with salivary gland carcinoma. There is no consensus on the standard treatment. METHODS: Patients with DMs were identified from an institutional database of 884 patients with salivary gland cancer who underwent resection of the primary tumor between 1985 and 2015. Survival outcomes for patients with DMs were determined with the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify factors associated with DM. RESULTS: Of the 884 patients identified, 137 (15%) developed DMs during follow-up. Most of the primary tumors (n = 77 [56%]) were located in a major salivary gland. At clinical presentation, 53% of the tumors were classified as T3 or T4, and 32% had clinical node metastases. The median time to DM was 20.3 months. The factors associated with shorter distant recurrence-free survival were male sex, high-risk tumor histology, and advanced pathological T and N classifications. Patients with bone metastases had a lower survival rate than patients with lung metastases. The total number of DMs in a patient was inversely associated with survival. Patients who underwent surgical resection of DMs had a significantly higher 5-year rate of metastatic disease-specific survival than patients who underwent observation or nonsurgical treatment (44%, 29%, and 19%, respectively; P = .003). CONCLUSIONS: In patients with DMs of salivary gland carcinoma, survival is negatively associated with high-grade histology, bone DMs, and the total number of DMs. Metastasectomy can help to lengthen disease-free survival.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32085934

RESUMO

BACKGROUND: There is a lack of evidence to guide appropriate donor sizing in recipients with moderate pulmonary hypertension (pHTN) awaiting heart transplantation (HTx). It is common practice to oversize donor hearts for such recipients to prevent post-operative right ventricular failure. Therefore, our objective was to determine if oversizing in pre-transplant moderate pHTN provides a survival advantage. METHODS: The United Network for Organ Sharing database was analyzed to include HTx recipients from 1994 to 2016. Recipients were considered as having moderate pHTN if the pulmonary vascular resistance (PVR) was 2.5 to 5 Wood units (WU) or transpulmonary gradient (TPG) was 10 to 18 mm Hg. Heart size mismatch was determined using the predicted heart mass equations. A size mismatch of ≥15% in either direction was considered undersized or oversized, respectively. Ninety-day and 1-year survival were analyzed based on size matching via univariate and Cox regression analysis. Propensity matching was performed to specifically evaluate the effect of donor sex among male transplant recipients. RESULTS: Among 29,441 HTx recipients, 10,666 had moderate pHTN by PVR criteria and 12,624 HTx patients had moderate pHTN according to TPG criteria. Among patients with a PVR of 2.5 to 5 WU, oversizing was not associated with lower mortality compared with matched hearts at 90 days (7.6% vs 7.4%; p = 0.75) and 1 year (12.1% vs 11.3%; p = 0.26). Conversely, undersizing the donor was associated with a higher 90-day (10.6% vs 7.6% vs 7.4%; p < 0.01) and 1-year (15.3% vs 12.1% vs 11.3%; p < 0.01) mortality than recipients receiving oversized or matched hearts, respectively. On Cox regression analysis, there was no benefit with oversizing at 90 days (hazard ratio [HR] 0.88; p = 0.23) and 1 year (HR 0.99; p = 0.90), whereas undersizing was associated with higher 90-day (HR 1.32; p = 0.02) and 1-year mortality (HR 1.23; p = 0.03) compared to size-matched controls. Among patients with moderate pHTN based on TPG of 10 to 18 mm Hg, neither undersizing nor oversizing was predictive of mortality at 90 days and 1 year according to Cox regression analysis. Propensity matching revealed that female-to-male transplantation had similar 1-year mortality to male-to-male transplantation, and there was no advantage to oversizing female donors for male recipients. CONCLUSIONS: In this registry-based analysis, there was no benefit to oversizing donors for cardiac transplant recipients with moderate pHTN. Elimination of this restriction could increase the donor pool and reduce wait times for such recipients.

9.
Thyroid ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31910129

RESUMO

Background: Retropharyngeal lymph node metastases (RPMs) from differentiated thyroid carcinoma (DTC) are rare. Treatment includes surgical resection, radioactive iodine (RAI) therapy, or external beam radiation therapy (EBRT). The objective of this study was to describe our experience in the management of DTC-associated RPMs. Methods: Patients diagnosed with a DTC-associated RPM from 1999 to 2018 were identified at our institution, using key search terms in imaging and histology reports. Patient and tumor characteristics were recorded, and patients were grouped according to RPM management: observation, nonsurgical treatment, or surgical resection. The estimated rates of local RPM control, disease-specific survival (DSS), and distant metastasis-free probability (DMFP) were calculated by using the Kaplan-Meier method. Results: Of the 65 patients identified, 53 (82%) had an RPM as a manifestation of recurrent disease. Twenty-five patients (38%) underwent observation, 13 (20%) received nonsurgical treatment (RAI, EBRT, and/or systemic therapy), and 27 (42%) underwent surgical resection. In the observation cohort, all patients had a stable RPM, which in the majority (80%) of cases remained <1.5 cm during the period of observation (median 28 months). Of the 13 patients in the nonsurgical treatment cohort, 3 received RAI therapy, 7 received EBRT, and 3 received systemic therapy only. In the surgical cohort, the median RPM maximum diameter was 2.0 cm (range 0.8-4.2 cm). The size of the RPM was predictive of surgical resection versus observation (p < 0.001). A transcervical approach was employed in 19 patients, and a transoral approach was used in 8 patients. The 5-year rate of local RPM control was 92%. For the whole cohort, the 5- and 10-year DMFP were 72% and 62%, respectively; the 5- and 10-year DSS were 93% and 81%, respectively. Conclusions: DTC-associated RPMs manifest as recurrent disease in the majority of patients. Select patients with a small-volume and nonprogressive RPM may be suitable for observation, whereas surgery is likely warranted in large or progressing RPMs. In general, the presence of an RPM from DTC appears to be associated with aggressive disease.

11.
Cancer ; 126(5): 994-1003, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31809562

RESUMO

BACKGROUND: Inflammation and immune surveillance evasion are cancer hallmarks. Peripheral blood leukocytes (PBLs) represent both. The aim of the current study was to examine PBLs as predictors of outcomes in oral cavity squamous cell carcinoma (OSCC), and to find specific cutoffs with the goal of including PBLs as host factor in patients' preoperative risk assessment. METHODS: Previously established head and neck squamous cell carcinoma (HNSCC) cutoffs were examined in an independent cohort of 1369 OSCC patients. Then optimal OSCC cutoffs were found and validated in the subset of patients with OSCC (n = 119) from the external HNSCC cohort. The PBLs analyzed were neutrophils, monocytes, and lymphocytes individually, the neutrophil-to-lymphocyte ratio (NLR), and a combined index using all PBLs called Systemic Inflammation Response Index (SIRI). RESULTS: All parameters were significant predictors of survival using the previous cutoffs. However, OSCC cutoffs stratified survival outcomes better. Considering neutrophils ≤4.8 × 109 /L as reference, patients with 4.8-9.1 × 109 /L neutrophils had 1.536 times higher risk of death (95% CI, 1.295-1.822), and patients with ≥9.1 × 109 /L had 3.076 times higher risk (95% CI: 2.170-4.360). All PBLs maintained independent prognostic capacity in multivariable analysis. Neutrophils, NLR, and SIRI were significant predictors of survival when validating OSCC cutoffs in the external validation cohort. CONCLUSIONS: Pretreatment peripheral blood neutrophils, NLR, and SIRI are the most robust independent predictors of overall survival among all PBLs in OSCC. The authors report externally validated cutoffs that demonstrate the feasibility of including PBLs as host features in the preoperative prognostication of OSCC.

12.
ASAIO J ; 66(3): 277-282, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30973402

RESUMO

Fibrinogen is a clotting factor and a major determinant of platelet aggregation. Albumin, on the other hand, inhibits platelet function and thrombus formation. Taken together, an elevated fibrinogen albumin ratio (FAR) has been described as a marker of disease severity during prothrombotic conditions. We evaluated the association of FAR and ischemic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. A single center, retrospective study was performed including all adult patients placed on VA ECMO. FAR was calculated from fibrinogen and albumin measurements in the first 24 hours of VA-ECMO initiation. Patients were categorized into high (≥125) and low (<125) FAR groups and the risk of eventual ischemic stroke was determined. There were 201 patients who underwent VA ECMO placement and 157 had a FAR. They were 56 ± 14 years old and 66 (42%) had a high FAR. Patients with a high FAR had lower survival free from an ischemic stroke during VA ECMO (log rank p < 0.001; adjusted hazard ratio 5.51; 95% CI: 1.8-16.5). In tertile analysis, the level of FAR was associated with an incrementally higher likelihood of eventual ischemic stroke (log rank p = 0.004). Those with a high FAR had greater mean platelet volume (10.8[10.4-12] vs. 10.5[10.2-11.9]fl, p = 0.004). An elevated FAR during the first 24 hours of VA ECMO placement is associated with a greater risk of a subsequent ischemic stroke. Our findings suggest that assessment of FAR soon after VA ECMO placement may assist with early stratification of patients at risk for an ischemic stroke.

14.
Surgery ; 167(1): 10-17, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31515125

RESUMO

BACKGROUND: Multifocality in papillary thyroid carcinoma is common. The aim of this study is to determine whether patients with multifocal disease, treated with lobectomy alone, have an increased risk of contralateral lobe papillary thyroid carcinoma, regional recurrence, and poorer survival. METHODS: After institutional review board approval, papillary thyroid carcinoma patients managed from 1986 to 2015 with lobectomy alone were identified from an institutional database. Papillary thyroid carcinoma patients with pT3 to T4 classification, nodal disease, or distant metastases were excluded. After excluding 40 patients who underwent an immediate completion thyroidectomy, 849 were included in the analysis; 619 (72.9%) had unifocal disease and 230 (27.1%) had multifocal disease. Contralateral lobe papillary thyroid carcinoma-free probability, regional recurrence-free probability, disease-specific survival, and overall survival were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 58 months, unifocal disease and multifocal disease patients had similar rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival (10-year contralateral lobe papillary thyroid carcinoma-free probability 98.6% vs 97.8%; regional recurrence-free probability 99.5% vs 99.4%; overall survival 91.6% vs 93.1%, respectively). There were no disease-related deaths. CONCLUSION: Select multifocal disease patients, managed with lobectomy alone, have rates of contralateral lobe papillary thyroid carcinoma, regional recurrence, and overall survival comparable to unifocal disease patients. Multifocal disease should not be an indication for completion thyroidectomy.

15.
Head Neck ; 42(1): 14-24, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31593349

RESUMO

BACKGROUND: This study aims to evaluate the impact of perioperative fluid administration, defined as fluid delivered intraoperatively and in the postanesthesia care unit, on postoperative outcomes. METHODS: Medical records of 102 patients with oral cavity squamous cell carcinoma undergoing free flap reconstruction between January 2011 and December 2015 were reviewed. The primary endpoint was development of a postoperative complication according to the Clavien-Dindo classification. Perioperative factors recorded were Washington University Head and Neck Comorbidity Index, operating time, vasopressor use, blood loss, intraoperative fluid, and perioperative fluid. RESULTS: Greater perioperative fluid administration was independently associated with surgical complications, flap complications, overall incidence of any complication, and increased length of stay. Greater intraoperative fluid administration was independently associated with higher rates of surgical complications. Intraoperative delivery of vasopressors was not associated with flap or surgical complications. CONCLUSION: Receiving less perioperative fluid was associated with fewer complications and decreased length of stay.

16.
Sci Adv ; 5(12): eaax5208, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31840066

RESUMO

Accurate detection and quantification of metastases in regional lymph nodes remain a vital prognostic predictor for cancer staging and clinical outcomes. As intratumoral heterogeneity poses a major hurdle to effective treatment planning, more reliable image-guided, cancer-targeted optical multiplexing tools are critically needed in the operative suite. For sentinel lymph node mapping indications, accurately interrogating distinct molecular signatures on cancer cells in vivo with differential levels of sensitivity and specificity remains largely unexplored. To address these challenges and demonstrate sensitivity to detecting micrometastases, we developed batches of spectrally distinct 6-nm near-infrared fluorescent core-shell silica nanoparticles, each batch surface-functionalized with different melanoma targeting ligands. Along with PET imaging, particles accurately detected and molecularly phenotyped cancerous nodes in a spontaneous melanoma miniswine model using image-guided multiplexing tools. Information afforded from these tools offers the potential to not only improve the accuracy of targeted disease removal and patient safety, but to transform surgical decision-making for oncological patients.

17.
Ann Thorac Surg ; 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31816283

RESUMO

BACKGROUND: The impact of different types of regional wall motion abnormalities(RWMAs) including Takotsubo-syndrome like(TTS-like) phenotype, on post-transplant outcomes when using donor hearts with transient left ventricular systolic dysfunction(LVSD) is unknown. We evaluated the prevalence, clinical characteristics, and prognostic association of different RWMAs including TTS-like hypokinesis, and post-transplant outcomes when using donor hearts with transient LVSD. METHODS: From all the adult(≥18 years) heart transplants in UNOS between January-2007 and September-2015, we identified 472 donor hearts with improving or transient LVSD- defined as LVEF≤40% on initial trans-thoracic echocardiogram(TTE) that improved to ≥50% on follow up TTE during donor evaluation. These improved LVSD donors were then sub-divided into 3 groups based on RWMAs on the initial TTE: TTS-like 49(10.38%), non-TTS RWMAs 74(15.68%) and diffuse global-hypokinesis(GH) 349(73.94%); and compared for baseline characteristics and post-transplant outcomes with follow up until June-2018. RESULTS: Donors with TTS-like LVSD were older and more likely to be female. The type of RWMA on initial TTE (including TTS-like) of transient LVSD donor hearts was not associated with 1-year or 5-year post-transplant mortality. Post-transplant functional status scores of recipients (at 1 year) and donor LVEF (at median follow up of 3.6 years) improved in all 3 sub-groups. Rates of stroke or pacemaker pre-discharge were also similar. CONCLUSIONS: In the largest analysis of transplanted donor hearts with transient LVSD, 1 in 4 had RWMAs on the initial TTE; but this was not associated with adverse post-transplant outcomes. Donor hearts with initial LVSD should be pursued irrespective of TTS-like hypokinesis or other RWMAs.

18.
Molecules ; 24(24)2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31847085

RESUMO

Selective targeting of anticancer drugs to the tumor site is beneficial in the pharmacotherapy of hepatocellular carcinoma (HCC). This study evaluated the prospective of galactosylated chitosan nanoparticles as a liver-specific carrier to improve the therapeutic efficacy of gemcitabine in HCC by targeting asialoglycoprotein receptors expressed on hepatocytes. Nanoparticles were formulated (G1-G5) by an ionic gelation method and evaluated for various physicochemical characteristics. Targeting efficacy of formulation G4 was evaluated in rats. Physicochemical characteristics exhibited by nanoparticles were optimal for administering and targeting gemcitabine effectively to the liver. The biphasic release behavior observed with G4 can provide higher drug concentration and extend the pharmacotherapy in the liver target site. Rapid plasma clearance of gemcitabine (70% in 30 min) from G4 was noticed in rats with HCC as compared to pure drug (p < 0.05). Higher uptake of gemcitabine predominantly by HCC (64% of administered dose; p < 0.0001) demonstrated excellent liver targeting by G4, while mitigating systemic toxicity. Morphological, biochemical, and histopathological examination as well as blood levels of the tumor marker, alpha-fetoprotein, in rats confirmed the curative effect of G4. In conclusion, this study demonstrated site-specific delivery and enhanced in vivo anti-HCC efficacy of gemcitabine by G4, which could function as promising carrier in hepatoma.

19.
Am Surg ; 85(9): 939-943, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31638503

RESUMO

Reoperative parathyroid surgery (REOPS) is often associated with lower cure rates and greater risk of nerve injury and hypoparathyroidism. The aim of this study was to evaluate cure rates, pathology, complications, and the efficacy of preoperative localization in patients requiring REOPS. Between 1992 and 2017, 2491 consecutive patients underwent parathyroidectomy for primary hyperparathyroidism. With Institutional Review Board approval, our prospectively collected parathyroidectomy outcomes database was queried for operative findings, outcomes, pathology, and localization methodology. Three hundred forty-six patients had REOPS (111 men/32% and 235 women/68%), with an overall cure rate of 91 per cent and a mean follow-up of 1.9 ± 0.7 years. The average preoperative serum calcium and parathyroid hormone were 11 ± 1 mg/dL and 373 ± 796 pg/mL, respectively. Normalization of intraoperative parathyroid hormone occurred in 248 patients and it was predictive of cure in 98.8 per cent of patients. A single adenoma was resected in 253 patients (75%), and the superior gland location was most common at 57 per cent. Ectopic glands were identified in only 33 patients. When preoperative imaging localized a lesion, a tumor was identified in that location in 75.4 per cent of sestamibi or SPECT/CT scans, 57.8 per cent of CT, 61.2 per cent of MRI, and 46.2 per cent of US. When at least two imaging modalities were concordant, sensitivity improved to 91.6 per cent (P < 0.001). Complication rates of permanent hypoparathyroidism and recurrent nerve palsy occurred in 0.03 per cent of patients. REOP for recurrent or persistent primary hyperparathyroidism has a cure rate of 91 per cent. Most missed parathyroid tumors are in the neck, and multimodal imaging improves preoperative localization and success.


Assuntos
Adenoma/cirurgia , Hiperparatireoidismo Primário/cirurgia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Reoperação , Adenoma/sangue , Adenoma/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/sangue , Feminino , Seguimentos , Humanos , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico por imagem , Hipoparatireoidismo , Masculino , Pessoa de Meia-Idade , Paralisia , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/sangue , Neoplasias das Paratireoides/diagnóstico por imagem , Paratireoidectomia/efeitos adversos , Complicações Pós-Operatórias , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Tecnécio Tc 99m Sestamibi , Adulto Jovem
20.
Bioconjug Chem ; 30(11): 2879-2888, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31647222

RESUMO

Twenty million Americans suffer from peripheral nerve injury caused by trauma and medical disorders, resulting in a broad spectrum of potentially debilitating side effects. In one out of four cases, patients identify surgery as the root cause of their nerve injury. Particularly during tumor resections or after traumatic injuries, tissue distortion and poor visibility can challenge a surgeon's ability to precisely locate and preserve peripheral nerves. Intuitively, surgical outcomes would improve tremendously if nerves could be highlighted using an exogeneous contrast agent. In clinical practice, however, the current standard of care-visual examination and palpation-remains unchanged. To address this unmet clinical need, we explored the expression of voltage-gated sodium channel Nav1.7 as an intraoperative marker for the peripheral nervous system. We show that expression of Nav1.7 is high in peripheral nerves harvested from both human and mouse tissue. We further show that modification of a Nav1.7-selective peptide, Hsp1a, can serve as a targeted vector for delivering a fluorescent sensor to the peripheral nervous system. Ex vivo, we observe a high signal-to-noise ratio for fluorescently labeled Hsp1a in both histologically prepared and fresh tissue. Using a surgical fluorescent microscope, we show in a simulated clinical scenario that the identification of mouse sciatic nerves is possible, suggesting that fluorescently labeled Hsp1a tracers could be used to discriminate nerves from their surrounding tissues in a routine clinical setting.

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