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1.
Head Neck ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119874

RESUMO

BACKGROUND: We aimed to identify predictors of distant metastatic recurrence (DMR) in patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) with nodal metastases treated with curative intent. METHODS: Predictors of DMR were identified using Cox regression in a multicenter study of 1151 patients. RESULTS: The 5-year risk of DMR was 9.6%. On multivariate analysis, immunosuppression (HR 2.93; 95% CI: 1.70-5.05; p < 0.001), nodal size >6 cm [versus ≤3 cm (HR 2.77; 95% CI: 1.09-7.03; p = 0.032)], ≥5 nodal metastases [versus 1-2 (HR 2.79; 95% CI: 1.63-4.78; p < 0.001)], and bilateral disease (HR 3.11; 95% CI: 1.40-6.90; p = 0.005) predicted DMR. A DMR risk score was developed that stratified risk from 6.6% (no risk factors) to 100% (≥3 risk factors) (p < 0.001). CONCLUSIONS: The risk of DMR in nodal metastatic HNcSCC increases with immunosuppression, nodal size >6 cm, ≥5 nodal metastases, and bilateral disease. A simple DMR risk score estimated prior to treatment may be clinically useful.

2.
Gland Surg ; 12(8): 1060-1066, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37701301

RESUMO

Background: Both subtotal parathyroidectomy (SPTX) and total parathyroidectomy with autotransplantation (TPTX + AT) are considered acceptable surgical approaches for renal patients. It is common that parathyroid surgery is performed in patients before they undergo kidney transplantation and there is currently no evidence considering the best surgical approach in this subset of patients. Methods: Two cohorts were identified of consecutive patients who underwent parathyroidectomy for renal hyperparathyroidism by two surgeons at a single institution over equivalent time periods (SPTX and TPTX + AT). A retrospective chart review was performed to assess these techniques, including outcomes following kidney transplantation. Results: There were 125 patients analysed, with 56 patients who underwent SPTX and 69 who underwent TPTX + AT. Both cohorts effectively reduced PTH post operatively. There were 22 patients in the SPTX cohort and 26 in the TPTX + AT cohort that subsequently received kidney transplants. There were no cases of recurrent hyperparathyroidism and one of hypoparathyroidism (4.5%) in the SPTX patients post-transplant. There was one case of recurrent hyperparathyroidism (3.8%) and four of persistent hypoparathyroidism (15.4%) in the TPTX + AT patients post-transplant. Conclusions: Surgery for renal hyperparathyroidism requires a careful balance of the extent of parathyroid resection to prevent persistent/recurrent disease and avoid permanent hypoparathyroidism. SPTX may be a more appropriate option in kidney transplant candidates in order to minimise the risk of long-term hypoparathyroidism.

3.
Front Endocrinol (Lausanne) ; 14: 1235243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600698

RESUMO

Aim: We seek a simple and reliable tool to predict malignant behavior of pheochromocytoma and paraganglioma (PPGL). Methods: This single-center prospective cohort study assessed size of primary PPGLs on preoperative cross-sectional imaging and prospectively scored specimens using the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS). Multiplication of PASS points with maximum lesion diameter (in mm) yielded the SIZEPASS criterion. Local recurrence, metastasis or death from disease were surrogates defining malignancy. Results: 76 consecutive PPGL patients, whereof 58 with pheochromocytoma and 51 female, were diagnosed at a mean age of 52.0 ± 15.2 years. 11 lesions (14.5%) exhibited malignant features at a median follow-up (FU) of 49 months (range 4-172 mo). Median FU of the remaining cohort was 139 months (range 120-226 mo). SIZEPASS classified malignancy with an area under the curve (AUC) of 0.97 (95%CI 0.93-1.01; p<0.0001). Across PPGL, SIZEPASS >1000 outperformed all known predictors of malignancy, with sensitivity 91%, specificity 94%, and accuracy 93%, and an odds ratio of 72 fold (95%CI 9-571; P<0.001). It retained an accuracy >90% in cohorts defined by location (adrenal, extra-adrenal) or mutation status. Conclusions: The SIZEPASS>1000 criterion is a lesion-based, clinically available, simple and effective tool to predict malignant behavior of PPGLs independently of age, sex, location or mutation status.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Glândulas Suprarrenais
4.
Surg Open Sci ; 14: 75-80, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37519329

RESUMO

Background: Despite technical advances, day surgery still accounts for <1 % of adrenal procedures. We investigated feasibility and safety of same day adrenalectomy (SDA). Methods: Between We recruited 30 patients with primary hyperaldosteronism (PHA) or Cushing's syndrome (CS) into a prospective matched, single centre cohort study to evaluate the impact of exposure to a same day discharge pathway (SDA cohort; n = 10) or inpatient adrenalectomy (PIPA cohort; n = 20). We compared results to a matched cohort (n = 40) from our prospective in-patient adrenalectomy registry (RIPA cohort). Results: Mean age was 51.3 ± 8.5 years, with 43 % female, 3.3 % ASA I and 96.7 % ASA II. Lesion size was 17 ± 9 mm (range 5-40 mm). 80 % of patients presented with PHA. The predefined primary endpoint (discharge on same calendar day without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, but none of the in-patients (χ2 = 57; p < 0.0001). The secondary endpoint (discharge within 23 h of surgery without major complications, emergency presentation or readmission) was achieved in 100 % of SDA, 90 % of PIPA (n.s.), 33 % of RIPA (33 %; χ2 = 14.6 p < 0.001), and 51.5 % of IPA patients (χ2 = 8.5 p < 0.01). Combining SDA and PIPA cohorts, 93.3 % of treatment episodes met widely used (WHO, United States) definitions of day surgery as completion of the hospital care episode within 23 h. Patients admitted for SDA were highly satisfied (100 %). Conclusion: Same day discharge after adrenalectomy is feasible, safe, and well-perceived in appropriately selected patients with PHA and Cushing's syndrome.

5.
Endocr Relat Cancer ; 30(4)2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621911

RESUMO

Parathyroid carcinoma is one of the least common endocrine malignancies and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. This review included 75 studies from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The 5-year overall survival ranged from 60 to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrant multidisciplinary management in a 'centre of excellence' with a track record in PC management.


Assuntos
Neoplasias das Paratireoides , Adulto , Humanos , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , Neoplasias das Paratireoides/terapia
6.
Cancers (Basel) ; 14(23)2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36497335

RESUMO

Parathyroid cancer (PC) is rare, but its pre-operative recognition is important to choose appropriate access strategies and achieve oncological clearance. This study characterizes features of mediastinal parathyroid cancer (MPC) and explores criteria aiding in the pre-operative recognition of malignancy. We assembled data from 502 patients with mediastinal parathyroid neoplasms (MPNs) from a systematic review of the literature 1968−2020 (n = 467) and our own patient cohort (n = 35). Thirty-two of the 502 MPNs (6.4%) exhibited malignancy. Only 23% of MPC patients underwent oncological surgery. Local persistence and early recurrence at a median delay of 24 months were frequent (45.8%), and associated with a 21.7-fold (95%CI 1.3−351.4; p = 0.03) higher risk of death due to disease. MPCs (n = 30) were significantly larger than cervical PC (n = 330), at 54 ± 36 mm vs. 35 ± 18 mm (χ2 = 20; p < 0.0001), and larger than mediastinal parathyroid adenomas (MPA; n = 226) at 22 ± 15 mm (χ2 = 33; p < 0.01). MPC occurred more commonly in males (60%; p < 0.01), with higher calcium (p < 0.01) and parathyroid hormone (PTH) levels (p < 0.01) than MPA. Mediastinal lesions larger than 3.0 cm and associated with a corrected calcium ≥ 3.0 mM are associated with a more than 100-fold higher odds ratio of being malignant (OR 109.2; 95%CI 1.1−346; p < 0.05). The composite 3 + 3 criterion recognized 74% of all MPC with an accuracy of 83%. Inversely, no MPN presenting with a calcium < 3.0 mM and size < 3.0 cm was malignant. When faced with pHPT in mediastinal location, consideration of the 3 + 3 rule may trigger an oncological team approach based on simple, available criteria.

7.
Cancers (Basel) ; 15(1)2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36612195

RESUMO

Long-term outcomes of parathyroid cancer remain poorly documented and unsatisfactory. This cohort includes 25 consecutive parathyroid cancer patients with median follow-up of 10.7 years (range 4.1−26.5 years). Pre-operative work-up in the center identified a suspicion of parathyroid cancer in 17 patients. En bloc resection, including the recurrent laryngeal nerve in 4/17 (23.5%), achieved cancer-free resection margins (R0) in 82.4% and lasting loco-regional disease control in 94.1%. Including patients referred after initial surgery elsewhere, R0 resection was achieved in merely 17/25 (68.0%) of patients. Cancer-positive margins (R1) in 8 patients led to local recurrence in 50%. On multivariate analysis, only margin status prevailed as independent predictor of recurrence free survival (χ2 19.5, p < 0.001). Local excision alone carried a 3.5-fold higher risk of positive margins than en bloc resection (CI95: 1.1−11.3; p = 0.03), and a 6.4-fold higher risk of locoregional recurrence (CI95: 0.8−52.1; p = 0.08). R1-status was associated with an 18.0-fold higher risk of recurrence and redo surgery (CI95: 1.1−299.0; p = 0.04), and a 22.0-fold higher probability of radiation (CI95: 1.4−355.5; p = 0.03). In patients at risk, adjuvant radiation reduced the actuarial risk of locoregional recurrence (p = 0.05). When pre-operative scrutiny resulted in upfront oncological surgery achieving cancer free margins, it afforded 100% recurrence free survival at 5- and 10-year follow-up, whilst failure to achieve clear margins caused significant burden by outpatient admissions (176 vs. 4 days; χ2 980, p < 0.001) and exposure to causes for concern (1369 vs. 0 days; χ2 11.3, p = 0.003). Although limited by cohort size, our study emphasizes the paradigm of getting it right the first time as key to improve survivorship in a cancer with excellent long-term prognosis.

8.
J Immunother Cancer ; 9(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34531247

RESUMO

BACKGROUND: We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer patients. METHODS: Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well as survival and tumor immunohistochemistry in dogs. Tumor biopsies were taken from human cancer patients on day 5 (all patients) and day 28 (some patients) of treatment and analyzed by histology. CT scans are provided from one patient. RESULTS: Significantly extended survival was observed in mouse P815 and 4T1 tumor models. Complete tumor regressions were observed in all three non-human species (6/186 (3%) of mouse mastocytomas; 3/14 (21%) of canine mastocytomas and 2/11 (18%) of equine melanomas). Evidence of systemic immune responses (regression of non-injected metastases) was also observed. Analysis of immune cells infiltrating mastocytoma tumors in mice showed that early neutrophil infiltration was predictive of treatment benefit. Analysis of the site of mastocytoma regression in dogs weeks or months after treatment demonstrated increased B and T cell infiltrates. Thus, activation of the innate immune system alone may be sufficient for regression of some injected tumors, followed by activation of the acquired immune system which can mediate regression of non-injected metastases. Finally, we report on the use of CFA in 12 human cancer patients. Treatment was well tolerated. CT scans showing tumor regression in a patient with late-stage renal cancer are provided. CONCLUSION: Our data demonstrate that intratumoral injection of CFA has major antitumor effects in a proportion of treated animals and is safe for use in human cancer patients. Further trials in human cancer patients are therefore warranted. Our novel treatment provides a simple and inexpensive cancer immunotherapy, immediately applicable to a wide range of solid tumors, and is suitable to patients in developing countries and advanced care settings.


Assuntos
Imunoterapia/métodos , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Cães , Feminino , Cavalos , Humanos , Masculino , Camundongos
9.
Oral Oncol ; 111: 104855, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32835932

RESUMO

OBJECTIVES: We aimed to determine if the number of nodal metastases is an independent predictor of survival in HNcSCC, whether it provides additional prognostic information to the AJCC N and TNM stage and identify optimal cut-points for risk stratification. MATERIALS AND METHODS: Retrospective multi-institutional cohort study of patients with parotid and/or cervical nodal metastases from HNcSCC treated with curative intent by surgery ±â€¯adjuvant therapy. The impact of number of nodal metastases on disease-specific and overall survival was assessed using multivariate Cox regression. Optimal cut-points for prognostic discrimination modelled using the AIC, BIC, C-index and PVE. RESULTS: The study cohort included 1128 patients, with 962 (85.3%) males, median age of 72.9 years (range: 18-100 years) and median follow-up 3.4 years. Adjuvant radiotherapy was administered to 946 (83.9%) patients. Based on objective measures of model performance, number of nodal metastases was classified as 1-2 (N = 816), 3-4 (N = 162) and ≥5 (N = 150) nodes. In multivariate analyses, the risk of disease-specific mortality progressively increased with 3-4 nodes (HR, 1.58; 95% CI: 1.03-2.42; p = 0.036) and ≥5 nodes (HR, 2.91; 95% CI: 1.99-4.25; p < 0.001) with similar results for all-cause mortality. This simple categorical variable provided superior prognostic information to the TNM stage. CONCLUSION: Increasing number of nodal metastases is an independent predictor of mortality in HNcSCC, with categorization as 1-2, 3-4 and ≥5 nodes optimizing risk stratification and providing superior prognostic information to TNM stage. These findings may aid in the development of future staging systems as well as identification of high-risk patients in clinical trials.


Assuntos
Linfonodos/patologia , Estadiamento de Neoplasias , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Comitês Consultivos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Pescoço , Neoplasias Parotídeas/secundário , Prognóstico , Radioterapia Adjuvante/estatística & dados numéricos , Análise de Regressão , Estudos Retrospectivos , Risco Ajustado , Neoplasias Cutâneas/terapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto Jovem
10.
Gland Surg ; 8(3): 226-236, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31328101

RESUMO

BACKGROUND: Vocal cord (VC) palsy following a thyroidectomy or parathyroidectomy can result in significant morbidity for the patient. We aimed to investigate the incidence of VC palsy in a tertiary referral Institution, track the management of these cases and record the long-term outcomes and VC recovery rates. METHODS: Retrospective review of all thyroidectomy/parathyroidectomy operations performed over 11 years. Patients with an unequivocal hoarse voice postoperatively were included. We analysed the patient's clinical characteristics and voice outcomes, operative, pathology and laryngoscopy reports during their follow-up. RESULTS: Ten patients fitted the inclusion criteria and were analysed. Median age at date of operation was 47.5 years (range, 16-81 years) and the M:F ratio was 1:2.3 (M:3, F:7). The median FU was 62.5 months (range, 12-144 months). The median hospital stay was 1.5 days (range, 1-87 days). There were 7 recurrent laryngeal nerve (RLN) injuries by manipulation, 1 case of RLN resection, 1 inadvertent division (with primary nerve repair) and 1 RLN was shaved off the thyroid. Long-term voice outcomes for the 7 patients with an RLN manipulation injury were: 3/7 patients had normal voice, 3/7 had moderate hoarseness and 1/7 had long-term hoarseness. The long-term voice outcome of the patient with RLN shaving off the thyroid gland was excellent while the 2 remaining patients (RLN resection and inadvertent division) needed 12 and 18 months respectively to achieve a normal quality of voice. Four out of the 10 patients had permanent VC palsy in the long-term and their voice outcomes varied: 1 patient had a normal voice, 2 patients had moderate hoarseness and 1 patient had persistent hoarseness. Only 1/10 patients did not show any voice improvement after 12 months. CONCLUSIONS: In the vast majority of cases post-operative hoarseness due to RLN palsy improves in the long-term, albeit voice may not return completely to normal.

11.
Ultrasound ; 26(2): 110-117, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30013611

RESUMO

PURPOSE: To identify the variant features encountered in parathyroid abnormalities and document those suggesting malignant change. MATERIALS AND METHODS: Data were collected from a cohort of patients who underwent investigation for primary hyperparathyroidism over a 10-year period. Ultrasonographic features: shape, presence of calcification, cystic changes, heterogeneous echogenicity, vascularity, capsular thickening, local invasion, and vascularity were reviewed retrospectively and were used to correlate with final histological findings. RESULTS: One hundred forty-seven patients with histology and concurrent ultrasonographic scans were reviewed, and divided into benign parathyroid lesions (nodular hyperplasia (n = 44), adenoma (n = 93)) and parathyroid carcinoma (n = 10). Parathyroid carcinomas were significantly larger than benign parathyroid lesions (P = 0.030). Benign parathyroid lesions showed variant sonographic features: irregular shape (16.8%), heterogenous echogenicity (24.1%), calcification (1.5%), capsular thickening (1.5%), and cystic change (19.7%). A significantly higher proportion of parathyroid carcinomas demonstrated heterogenous echogenicity (P = 0.022), capsular thickening (P = 0.023), and infiltrative margin (P < 0.0001) than benign parathyroid lesions. Of the 137 benign parathyroid lesions, 38 (27.7%), 76 (55.5%), 23 (16.8%) were avascular, vascular, and hypervascular, respectively. Of the 10 parathyroid carcinomas, 4 (40%), 3 (30%), and 3 (30%) of lesions were avascular, vascular, and hypervascular, respectively. The vascularity of the lesions did not differ significantly between the parathyroid carcinoma and benign parathyroid lesions (P = 0.281). CONCLUSION: Ultrasonographic features such as irregular shape, heterogeneous echogenicity, cystic change, and vascularity are nondiscriminatory features between benign or malignant lesions. Large lesion size together with the presence of calcification, capsular thickening, or infiltrative margin strongly raises the suspicion of a malignant parathyroid lesion, and management should be altered.

12.
Clin Chem ; 63(12): 1836-1846, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28904054

RESUMO

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy, with an annual incidence of 1 or 2 cases per million. Biochemical diagnosis is challenging because up to two-thirds of the carcinomas are biochemically silent, resulting from de facto enzyme deficiencies in steroid hormone biosynthesis. Urine steroid profiling by GC-MS is an effective diagnostic test for ACC because of its capacity to detect and quantify the increased metabolites of steroid pathway synthetic intermediates. Corresponding serum assays for most steroid pathway intermediates are usually unavailable because of low demand or lack of immunoassay specificity. Serum steroid analysis by LC-MS/MS is increasingly replacing immunoassay, in particular for steroids most subject to cross-reaction. METHODS: We developed an LC-MS/MS method for the measurement of serum androstenedione, corticosterone, cortisol, cortisone, 11-deoxycorticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, and testosterone. Assay value in discriminating ACC from other adrenal lesions (phaeochromocytoma/paraganglioma, cortisol-producing adenoma, and lesions demonstrating no hormonal excess) was then investigated. RESULTS: In ACC cases, between 4 and 7 steroids were increased (median = 6), and in the non-ACC groups, up to 2 steroids were increased. 11-Deoxycortisol was markedly increased in all cases of ACC. All steroids except testosterone in males and corticosterone and cortisone in both sexes were of use in discriminating ACC from non-ACC adrenal lesions. CONCLUSIONS: Serum steroid paneling by LC-MS/MS is useful for diagnosing ACC by combining the measurement of steroid hormones and their precursors in a single analysis.


Assuntos
Neoplasias do Córtex Suprarrenal/sangue , Carcinoma Adrenocortical/sangue , Esteroides/sangue , Espectrometria de Massas em Tandem/métodos , Neoplasias do Córtex Suprarrenal/diagnóstico , Carcinoma Adrenocortical/diagnóstico , Adulto , Idoso , Cromatografia Líquida/métodos , Feminino , Humanos , Limite de Detecção , Masculino , Pessoa de Meia-Idade
13.
J Ultrasound ; 17(4): 307-11, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25368690

RESUMO

A phaeochromocytoma is a rare catecholamine-secreting tumour arising from the chromaffin cells. We describe a case of a child with Von Hippel-Lindau disease, with an adrenal phaeochromocytoma who presented with severe dilated cardiomyopathy driven by secondary hypertension. Contrast-enhanced ultrasound findings are described and compared with both magnetic resonance imaging and computed tomography imaging.

14.
Curr Atheroscler Rep ; 16(11): 455, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25236775

RESUMO

Bariatric surgery has helped patients attain not only significant and sustained weight loss but has also proved to be an effective means of mitigating or reversing various obesity-related comorbidities. The impressive rates of remission or resolution of type 2 diabetes mellitus (T2D) following bariatric surgery are well documented and have rightly received great attention. Less understood are the effects of bariatric surgery on cardiovascular disease (CVD) and its underlying risk factors. Thanks to the availability of increasingly sensitive laboratory tools, the emerging science of lipidomics and metagenomics is poised to offer significant contributions to our understanding of metabolically induced vascular diseases. They are set to identify novel mechanisms explaining how the varied approaches of bariatric surgery produce the remarkable improvements in multiple organs observed during patient follow-up. This article reviews recent and novel findings in patients through the lens of lipidomics with an emphasis on CVD.


Assuntos
Cirurgia Bariátrica , Doenças Cardiovasculares/cirurgia , Diabetes Mellitus Tipo 2/cirurgia , Metabolismo dos Lipídeos/fisiologia , Obesidade/cirurgia , Humanos , Fatores de Risco
15.
BMJ Case Rep ; 20142014 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-24849634

RESUMO

A 59-year-old man with a giant recurrent intrathoracic goitre was admitted for completion thyroidectomy for recurrent severe retrosternal pain. The patient had undergone a cervical thyroidectomy elsewhere 13 years earlier, during which only the cervical part of the goitre had been resected. Owing to the previous operation with an expected scar around the innominate vein, and the goitre's size and localisation obstructing the upper chest aperture, we chose an alternate access. Clamshell thoracotomy with reverse sternotomy allows central vascular control and excision of large goitres bypassing predictable problems at the cervicothoracic junction. Surgery was performed with minimal blood loss and with excellent functional outcome. The described access adds to the repertoire to deal with this unusual situation.


Assuntos
Bócio Subesternal/cirurgia , Esternotomia/métodos , Toracotomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
16.
Clin Endocrinol (Oxf) ; 81(3): 343-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24712713

RESUMO

BACKGROUND: Adrenocortical neoplasms are classically divided into adenomas (ACA) and carcinomas (ACC). Heterogeneous appearance and greater size are criteria to suggest malignancy, along with the urinary steroid profile (USP). The presence of regression and myelolipomatous changes in adenomas (ACA-RML) can contribute to confusion with ACC and its USP remains unknown. OBJECTIVE: To evaluate the features of ACA-RML in comparison with other adrenocortical neoplasms. METHODS: We selected consecutive ACA (11), ACA-RML (7) and ACC (13) cases for which USP analysis was performed before surgery and tissue was available for histological evaluation (King's College Hospital, 2005-2012). Cases were classified according to WHO and Armed Forces Institute of Pathology criteria. USPs were obtained by gas chromatography/mass spectrometry. Total excretion of individual steroids and indices (sums and ratios chosen to reflect steroid metabolic activity) were compared between ACA-RML, ACA and ACC. RESULTS: In comparison with ACA, tumours in ACA-RML were significantly larger (8·5 ± 2·4 vs 3·5 ± 1·0, P = 0·002), presented in older patients and showed relatively higher incidence in males. Mitotic figure counts were significantly lower (0·39 ± 0·04 vs 0·93 ± 0·11 in ACA, P = 0·001) and revealed higher frequency of apoptotic cells (100% vs 9% in ACA, P = 0·001). The USP of ACA-RML showed no diagnostic features of ACC. No differences from ACA were significant, but there was a tendency towards lower dehydroepiandrosterone DHA and DHA metabolites. CONCLUSIONS: ACA-RML reveals distinctive histological features and lack of USP markers of malignancy. More cases of this rare tumour may confirm differences from ACA in steroid excretion. It is important to recognize ACA-RML because its size and heterogeneous appearance raise the possibility of ACC.


Assuntos
Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/urina , Adulto , Idoso , Desidroepiandrosterona/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esteroides/urina
17.
Proc Natl Acad Sci U S A ; 111(7): 2686-91, 2014 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-24492375

RESUMO

The immune system plays an instrumental role in obesity and insulin resistance. Here, we unravel the role of the costimulatory molecule CD40 and its signaling intermediates, TNF receptor-associated factors (TRAFs), in diet-induced obesity (DIO). Although not exhibiting increased weight gain, male CD40(-/-) mice in DIO displayed worsened insulin resistance, compared with wild-type mice. This worsening was associated with excessive inflammation of adipose tissue (AT), characterized by increased accumulation of CD8(+) T cells and M1 macrophages, and enhanced hepatosteatosis. Mice with deficient CD40-TRAF2/3/5 signaling in MHCII(+) cells exhibited a similar phenotype in DIO as CD40(-/-) mice. In contrast, mice with deficient CD40-TRAF6 signaling in MHCII(+) cells displayed no insulin resistance and showed a reduction in both AT inflammation and hepatosteatosis in DIO. To prove the therapeutic potential of inhibition of CD40-TRAF6 in obesity, DIO mice were treated with a small-molecule inhibitor that we designed to specifically block CD40-TRAF6 interactions; this compound improved insulin sensitivity, reduced AT inflammation, and decreased hepatosteatosis. Our study reveals that the CD40-TRAF2/3/5 signaling pathway in MHCII(+) cells protects against AT inflammation and metabolic complications associated with obesity whereas CD40-TRAF6 interactions in MHCII(+) cells aggravate these complications. Inhibition of CD40-TRAF6 signaling by our compound may provide a therapeutic option in obesity-associated insulin resistance.


Assuntos
Antígenos CD40/metabolismo , Resistência à Insulina/imunologia , Obesidade/imunologia , Transdução de Sinais/imunologia , Fator 6 Associado a Receptor de TNF/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Análise de Variância , Animais , Compostos Azo , Antígenos CD40/antagonistas & inibidores , Antígenos CD40/genética , Linfócitos T CD8-Positivos/imunologia , Calorimetria , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Citometria de Fluxo , Ligantes , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/complicações , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Ressonância de Plasmônio de Superfície , Fator 6 Associado a Receptor de TNF/antagonistas & inibidores
18.
Clin Nucl Med ; 39(3): 237-42, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24445273

RESUMO

AIM: The aim of this study was to assess the utility of combined C-methionine and F-FDG PET/CT imaging in hyperparathyroidism. PATIENTS AND METHODS: We reviewed all scans performed for hyperparathyroidism with both C-methionine and F-FDG PET/CT or PET in our institution since 1993. Forty-three patients (47 pairs of scans) were included (13 men and 30 women) with a mean age of 63 years. C-methionine and F-FDG PET/CT scans were classified as positive or negative for localization of abnormal parathyroid tissue, and the site of uptake was noted in the positive scans. Other concurrent imaging (Tc-MIBI scintigraphy, ultrasonography, CT, or MRI) findings were also noted when performed. Clinical follow-up information was available in 27 patients (30 episodes). RESULTS: Of the 47 PET scan episodes, 23 (49%) were positive. Twenty-two C-methionine scans showed abnormal focal localization of which 10 also showed concordant abnormal F-FDG uptake. One patient was positive with F-FDG and negative with C-methionine.Of the 16 patients who underwent subsequent surgery, 6 had concordant C-methionine, F-FDG, and surgical findings; 6 had concordant C-methionine and surgical findings; 1 had concordant F-FDG and surgical findings; and 3 had both PET scans negative but had adenomas excised during surgery.Of the 3 with both PET scans negative and discordant surgical findings, 1 had mediastinal parathyroid lipoadenoma excised and 2 had normally sited parathyroid adenoma excised. CONCLUSIONS: F-FDG PET/CT rarely provides additional information and could be saved for patients in whom C-methionine PET/CT is negative.


Assuntos
Fluordesoxiglucose F18 , Hiperparatireoidismo/diagnóstico por imagem , Metionina , Tomografia por Emissão de Pósitrons , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Hiperparatireoidismo/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/diagnóstico por imagem , Radiografia
19.
Endocr Pract ; 18(5): e130-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22982783

RESUMO

OBJECTIVE: To describe a patient with hereditary head and neck paraganglioma (HNPGL) and to review the literature on these rare tumors. METHODS: We review the English-language literature regarding SDH mutations, HNPGL, hereditary paraganglioma-pheochromocytoma syndrome, and the role of functional imaging in the follow-up of these tumors. We also describe the clinical findings, imaging results, and follow-up of a man who initially presented with HNPGL and subsequently developed metastatic pheochromocytoma 20 years later. RESULTS: A 66-year-old man presented with a history of hypertension, palpitations, sweating, and elevated urinary norepinephrine. Iodine-123-metaiodobenzylguanidine (123I-MIBG) scan demonstrated a left suprarenal mass and multiple avid lesions in the abdomen, chest, and posterior cranial fossa. Histologic examination confirmed a metastatic pheochromocytoma, and molecular genetic testing revealed a mutation in the SDHD gene. The patient had had surgery 20 years earlier for HNPGL. Although most HNPGLs arise sporadically, susceptibility genes have been identified in approximately one-third of cases. Optimal follow-up remains controversial. We reiterate a need for long-term follow-up of patients with a mutation in an SDH gene. 123I-MIBG, highly specific for identifying ectopic neuroendocrine tissue, may have a role in long-term follow-up. CONCLUSIONS: Although HNPGLs rarely metastasize, their malignant potential is difficult to predict. Routine surveillance for at-risk patients is recommended. Patients with a mutation in an SDH gene should therefore undergo regular surveillance.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Paraganglioma/diagnóstico , Paraganglioma/genética , Succinato Desidrogenase/genética , Idoso , Humanos , Masculino , Mutação
20.
Nat Rev Endocrinol ; 8(10): 612-22, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22751344

RESUMO

Parathyroid cancer is rare, but often fatal, as preoperative identification of malignancy against the backdrop of benign parathyroid disease is challenging. Advanced genetic, laboratory and imaging techniques can help to identify parathyroid cancer. In patients with clinically suspected parathyroid cancer, malignancy of any individual lesion is established by three criteria: demonstration of metastasis, specific ultrasonographic features, and a ratio >1 for the results of third-generation:second-generation parathyroid hormone assays. Positive findings for all three criteria dictate an oncological surgical approach, as appropriate radical surgery can achieve a cure. Mutation screening pinpoints associated conditions and asymptomatic carriers. Molecular profiling of tumour cells can identify high-risk features, such as differential expression of specific micro-RNAs and proteins, and germ line mutations in CDC73, but is unsuitable for preoperative assessment owing to the potential risks associated with biopsy. A validated, histopathology-based prognostic classification can identify patients in need of close follow-up and adjuvant therapy, and should prove valuable to stratify clinical trial cohorts: low-risk patients rarely die from parathyroid cancer, even on long-term follow-up, whereas 5-year mortality in high-risk patients is around 50%. This insight has improved the approach to parathyroid cancer by enabling risk-adapted surgery and follow-up.


Assuntos
Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/genética , Cálcio/sangue , Mutação em Linhagem Germinativa/genética , Humanos , Mutação , Proteínas Supressoras de Tumor/genética
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