RESUMO
BACKGROUND: Central pancreatectomy (CP) is a parenchymal-sparing technique indicated for the resection of selected lesions of the neck or proximal body of the pancreas.1,2 The risk of postoperative complications is theoretically doubled because the surgeon has to manage two cut surfaces of the pancreas. The video shows a fully robotic CP to treat a 62-year-old male patient with a mixed-type intraductal papillary mucinous neoplasm (IPMN) of the pancreatic neck, using ultrasound (US) and Wirsung endoscopic evaluation to guide the pancreatic resection and ensure optimal resection margins. MATERIALS AND METHODS: A US-guided robotic CP was carried out, and an intraoperative endoscopic evaluation of the MPD was performed to determine the distal transection level. A transmesocolic, end-to-side, robot-sewn Wirsung-jejunostomy with internal MPD stenting was then created. The procedure was completed with a side-to-side jejunojejunostomy. RESULTS: The operative time was 290 min, with negligible blood loss. During the postoperative course, the patient experienced bleeding from a branch of the gastroduodenal artery with subsequent fluid collection, which was successfully treated with angioembolization and percutaneous drainage. He was discharged home on postoperative day 22. Final pathology revealed a non-invasive IPMN with low-grade dysplasia and free surgical margins. At 12 months of follow-up, the patient was doing well, with no evidence of local recurrence and endocrine or exocrine pancreatic insufficiency. CONCLUSIONS: The combination of robotic surgery with intraoperative US and Wirsungoscopy may offer distinct technical advantages for challenging pancreatectomies that follow the principles of parenchymal-sparing surgery.
Assuntos
Pancreatectomia , Ductos Pancreáticos , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Pancreatectomia/métodos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Ductos Pancreáticos/cirurgia , Ductos Pancreáticos/patologia , Ductos Pancreáticos/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/cirurgia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/diagnóstico por imagem , PrognósticoRESUMO
Central pancreatectomy (CP) is indicated for benign or low-grade pancreatic tumors located in the neck or proximal pancreatic body. This procedure is demanding and has a high rate of postoperative complications. Minimally invasive surgery is now commonly used for CP but it is still unclear whether the robotic approach offers any advantages over conventional pancreatic minimally invasive surgery. Most studies on robotic CP are limited to case reports or case series; however, there are two important studies on this topic. Currently, the evidence on robotic CP remains limited, making it challenging to draw definitive conclusions in favor of one technique over the other. The use of a robotic platform, with its integrated tools such as intraoperative ultrasound, can guide the surgeon in performing this technically demanding procedure in a safer manner. The controversy regarding the best minimally invasive surgery approach for CP is still ongoing and requires further research.
Assuntos
Pancreatectomia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/prevenção & controle , PrognósticoRESUMO
AIM: Ensuring an adequate distal resection margin (DRM) is a key factor in achieving the gold standard in surgical treatment for rectal surgery. The aim of this article is to describe our surgical technique and the usefulness of intraoperative ultrasonography (IOUS) for evaluating the DRM during robotic rectal surgery (RRS). METHOD: Prospective data on five consecutive patients with rectal cancer who underwent RRS between January 2023 and December 2023 were collected. IOUS was utilized to evaluate the DRM in all patients. RESULTS: The mean time for the IOUS examination ranged from 5 to 10 min. There were no intraoperative complications or conversions to open surgery. The median length of hospital stay was 6.4 days (±1.67 days). During hospitalization, one patient experienced a Grade II complication according to the Clavien-Dindo classification, specifically postoperative ileus. Furthermore, one patient experienced a delayed anastomotic fistula, which was conservatively treated without readmission. At definitive pathology, the median distance of the tumour from the DRM was 29 mm (±1.41 mm) and all patients had an R0 resection. CONCLUSION: IOUS is a reproducible and helpful modality for identifying the distal margin of the cutting line during robotic resection of rectal cancers. It does not affect the operating time compared with other methods and could be an alternative method for assessment of the DRM during RRS.
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BACKGROUND: Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease. METHODS: In a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves' ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful). RESULTS: A total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (-2.82 mm vs. -0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation. CONCLUSIONS: Among patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.).
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Receptor IGF Tipo 1/antagonistas & inibidores , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Diplopia/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Exoftalmia/tratamento farmacológico , Oftalmopatia de Graves/diagnóstico por imagem , Humanos , Análise de Intenção de Tratamento , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Órbita/diagnóstico por imagem , Receptor IGF Tipo 1/imunologia , AutorrelatoRESUMO
BACKGROUND: The adoption of robotic surgery for esophageal cancer has been expanding rapidly over the recent years. In the setting of two-field esophagectomy, different techniques exist for intrathoracic esophagogastric anastomosis, although the superiority of one over another has not been clearly demonstrated. Potential benefits in terms of anastomotic leakage and stenosis have been reported in association with a linear-stapled anastomosis as compared to the more widespread techniques of circular mechanical and hand-sewn reconstructions, however, there is still limited reported evidence on its application to robotic surgery. We here report our fully robotic technique of side-to-side, semi-mechanical anastomosis. METHODS: All consecutive patients undergoing fully robotic esophagectomy featuring intrathoracic side-to-side stapled anastomosis by a single surgical team were included in this analysis. Operative technique is detailed, and perioperative data are assessed. RESULTS: A total of 49 patients were included. There were no intraoperative complications and no conversion occurred. The rate of overall postoperative morbidity was 25, 14% being the relative rate of major complications. With anastomotic-related morbidity in particular, one patient developed minor anastomotic leakage. CONCLUSIONS: Our experience demonstrates that a linear, side-to-side fully robotic stapled anastomosis can be created with a high technical success and minimal incidence of anastomosis-related morbidity.
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Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Humanos , Esofagectomia/efeitos adversos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/etiologia , Fístula Anastomótica/prevenção & controle , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento , Anastomose Cirúrgica/efeitos adversos , Neoplasias Esofágicas/complicações , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
PURPOSE: Graves orbitopathy (GO) is the most common extrathyroidal manifestation of Graves disease. Although its pathogenesis is not fully elucidated, GO is commonly considered an autoimmune disease due to loss of self-tolerance against autoantigens shared by thyroid epithelial cells and orbital fibroblasts. High-dose intravenous glucocorticoids (ivGCs) are the most used treatment for moderate-to-severe, active GO, but the addition of other immunomodulating treatments can improve the efficacy of ivGCs. Among the various risk factors that can affect the occurrence of GO, cholesterol may be worthy of interest. Since 2015 the role of cholesterol and cholesterol-lowering medications has been investigated. The purpose of this review is to discuss this topic, thereby offering new therapeutic opportunities for patients with GO. METHODS: We searched PubMed for studies published between January 1, 1980 and June 1, 2023, using the search terms "Graves orbitopathy," "thyroid eye disease," "Graves ophthalmopathy," "thyroid ophthalmopathy," "thyroid-associated ophthalmopathy," "endocrine ophthalmopathy," "cholesterol," "lipids," "statins," "low-density lipoprotein," "atorvastatin," and "cholesterol-lowering drugs." Only English-language articles were included. RESULTS: A correlation between low-density lipoprotein cholesterol and the risk of GO development has been reported. Furthermore, low-density lipoprotein cholesterol has been proposed as a risk factor that can affect the course of GO and the response to ivGCs. The protective role of cholesterol-lowering medications in preventing GO has been also investigated. Statin treatment was found to have potential benefits in reducing the risk of GO in patients with Graves disease. Given these findings, measurement of low-density lipoprotein cholesterol and treatment of hypercholesterolemia in patients with moderate-to-severe, active GO may be considered before starting ivGCs administration. Recently, a randomized clinical trial aimed at investigating the effects of statins in GO suggested that the addition of oral atorvastatin to ivGCs improves the overall outcome of moderate-to-severe, active GO in hypercholesterolemic patients given ivGCs. CONCLUSIONS: Overall, statins seem to have a preventive and therapeutic role in moderate-to-severe active GO. Their efficacy can be related to cholesterol-lowering activity, pleiotropic actions, and interaction with methylprednisolone.
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Doença de Graves , Oftalmopatia de Graves , Inibidores de Hidroximetilglutaril-CoA Redutases , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Oftalmopatia de Graves/tratamento farmacológico , Atorvastatina , Glucocorticoides/uso terapêutico , Lipoproteínas LDL , Colesterol , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.
Assuntos
Exoftalmia , Oftalmopatia de Graves , Anticorpos Monoclonais Humanizados/uso terapêutico , Diplopia , Oftalmopatia de Graves/tratamento farmacológico , HumanosRESUMO
INTRODUCTION: Dysthyroid optic neuropathy (DON) is the most severe complication of Graves' orbitopathy (GO) and its management may require decompression surgery. Clear recommendations do not exist about which surgery should be performed and how extended the decompression should be. In this paper we present our experience regarding the management of DON via 3 different surgical protocols: a modified extended orbital apex decompression, a 2 walls decompression (inferior and lateral) and a 3 walls decompression (inferior, lateral and medial) and evaluate the functional outcomes. METHODS: Retrospective evaluation of subjects affected by DON not responding to medical therapy has been performed. All patients were submitted to pre- and post-operative ophthalmologic evaluations and orbital and sinuses CT scan in order to evaluate functional and surgical outcomes. RESULTS: 27 patients were enrolled in the study. Surgical procedures were performed on 42 orbits. A statistically significant post-operative improvement was recorded in visual acuity, proptosis, color vision and fundus oculi evaluation for all groups. No patient developed major or minor complications after surgery. CONCLUSIONS: Extended endonasal approach and 3 walls decompression have been proved effective in the management of DON. The choice between them is done according to degree of proptosis, general status and eye-surface damages.
Assuntos
Exoftalmia , Oftalmopatia de Graves , Doenças do Nervo Óptico , Descompressão Cirúrgica/métodos , Exoftalmia/cirurgia , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/cirurgia , Humanos , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/cirurgia , Órbita/cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: Graves' orbitopathy (GO) reflects an autoimmune response against antigens expressed by the thyroid and orbital tissues. Elimination of thyroid antigens may be beneficial for GO. Total thyroid ablation (TTA) [thyroidectomy (Tx), followed by 30 mCi of radioiodine] was shown to exert a beneficial effect on GO following intravenous glucocorticoids (ivGC) compared with Tx alone. Here, we investigated retrospectively whether TTA performed with a 15 mCi of radioiodine still maintains advantages over Tx. METHODS: Thirty-two subjects, 13 treated with TTA (performed with 15 mCi of radioiodine) and 19 with Tx alone, all with moderately severe, active GO, treated with ivGC, were studied. The primary objective was the outcome of GO at 24 weeks based on a composite evaluation. RESULTS: The two groups did not differ at baseline in terms of sex, age, smoking habits, TSH, anti-TSH receptor autoantibodies, GO duration and eye features. The proportion of GO responders at 24 weeks was greater in the TTA (61.5%) than in the Tx group (26.3%, P = 0.046). In contrast, GO outcome at 48 weeks did not differ between the two groups (69.2% vs 52.6% of responder in TTA and Tx group, respectively). The outcome of the individual GO features did not differ between the two groups both a 24 and 48 months. CONCLUSIONS: The advantage of total thyroid ablation seems to be a more rapid response for GO to ivGC treatment. Prospective, randomized studies in a larger number of subjects are needed to confirm our findings.
Assuntos
Técnicas de Ablação/métodos , Glucocorticoides/administração & dosagem , Oftalmopatia de Graves , Radioisótopos do Iodo/uso terapêutico , Tireoidectomia/métodos , Administração Intravenosa , Terapia Combinada , Relação Dose-Resposta à Radiação , Feminino , Oftalmopatia de Graves/sangue , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/terapia , Humanos , Imunoglobulinas Estimuladoras da Glândula Tireoide/sangue , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
PURPOSE: To compare optic disc, retinal and choroidal measurements in patients with Graves' disease with or without orbitopathy, and healthy controls. METHODS: Optical coherence tomography and Heidelberg retinal tomography were performed in 40 patients with Graves' orbitopathy (GO), 40 subjects with Graves's disease (GD) with no sign of orbitopathy and 40 healthy controls. Degree of exophthalmos, ocular alignment, clinical activity score (CAS), choroidal thickness, retinal thickness, ganglion cell layer (GCL) thickness, disc area, cup area, rim area, cup/disc area ratio, linear cup/disc ratio and mean peripapillary retinal nerve fibre layer thickness were analysed. RESULTS: GO patients and healthy controls significantly differ regarding mean central retinal thickness (275 ± 19 µm and 285 ± 20 µm, P = 0.017); mean central GCL thickness (14.87 ± 3.0 µm and 17.92 ± 5.02 µm, P = 0.001); mean disc area (2.00 ± 0.44 mm2 and 1.72 ± 0.37 mm2, P = 0.003); mean cup area (0.53 ± 0.52 mm2 and 0.31 ± 0.20 mm2, P = 0.003); cup/disc area ratio (0.22 ± 0.10 and 0.17 ± 0.08, P = 0.010); and linear cup/disc ratio (0.47 ± 0.15 and 0.40 ± 0.13, respectively, P = 0.011). No difference was found between patients without orbitopathy and healthy controls. No significant difference was found regarding the choroidal thickness between the three groups. There was no statistically significant relationship between retinal thickness, ganglion cell layer thickness, mean disc area, mean cup area, cup/disc area ratio, linear cup/disc ratio, CAS, exophthalmometric value and ocular alignment. CONCLUSION: GO patients showed significant changes in foveal and GCL thickness, and optic nerve head morphology suggesting a possible influence of the orbital inflammatory process.
Assuntos
Oftalmopatia de Graves , Disco Óptico , Estudos Transversais , Oftalmopatia de Graves/complicações , Oftalmopatia de Graves/diagnóstico , Humanos , Retina , Tomografia de Coerência ÓpticaRESUMO
Based on the role of oxidative stress in the pathogenesis of Graves' hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent selenium has been proposed and several studies on the subject have been conducted, both in vitro and in vivo. Whereas a true benefit related to the use of selenium in patients with Graves' hyperthyroidism has been questioned, its use in patients with mild Graves' orbitopathy is generally believed to be beneficial because of which selenium has entered in the clinical practice for this eye condition.
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Oftalmopatia de Graves/tratamento farmacológico , Selênio/uso terapêutico , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Estresse Oxidativo , Qualidade de Vida , Selênio/farmacologia , Inquéritos e QuestionáriosRESUMO
PURPOSE: To review the in vitro and in vivo studies supporting a role of selenium for the treatment of mild Graves orbitopathy. METHODS: Review of the current literature on the role of selenium in the management of Graves orbitopathy. RESULTS: Graves orbitopathy (GO) is a disfiguring and disabling disorder usually observed in patients with Graves hyperthyroidism, and more rarely in patients with hypothyroid autoimmune thyroiditis or in the absence of overt thyroid dysfunction. Noninvasive treatments include intravenous glucocorticoids and orbital radiotherapy and are generally offered to patients with moderately severe GO. In contrast, patients with mild GO are generally treated only with local measures. Thus, the benefits of intravenous glucocorticoids in mild GO are limited and do not justify the risks that the treatment carries. However, a medical treatment for mild GO is heavily wanted, as a relevant proportion of patients have a significant decrease in their quality of life, and GO can progress into more severe forms. Because of the role of oxidative stress in the pathogenesis of GO, an antioxidant approach has been proposed and the antioxidant agent selenium has been shown to be effective for GO. CONCLUSION: Studies have shown that a 6-month course of sodium selenite can improve the course of mild GO and prevent deterioration when compared with placebo.
Assuntos
Gerenciamento Clínico , Oftalmopatia de Graves/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ácido Selenioso/uso terapêutico , Oftalmopatia de Graves/metabolismo , Humanos , Oligoelementos/uso terapêutico , Resultado do TratamentoAssuntos
Doença Diverticular do Colo , Diverticulite , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Diverticulite/cirurgia , Colo Sigmoide/cirurgia , Biópsia , Doença Diverticular do Colo/complicações , Doença Diverticular do Colo/cirurgiaRESUMO
OBJECTIVE: Intravenous (iv) glucocorticoids (GC) (ivGC) are used for active Graves orbitopathy (GO), but factors affecting GO outcome are poorly understood. We performed a retrospective study to investigate the variables affecting GO after ivGC. METHODS: We evaluated 83 consecutive GO patients treated with ivGC but not orbital radiotherapy (ORT) and re-examined them after a median of 47 months. The endpoints were the relationships between GO outcome or additional treatments with age, sex, smoking habits, thyroid volume, thyroid treatment, time since thyroid treatment, antithyroid-stimulating hormone receptor antibodies (TRAb), GO duration, GO features, and follow-up time. RESULTS: GO features improved after treatment, resulting in moderate and marked amelioration in ~75% and ~41% of patients respectively. By multivariate analysis, a moderate GO improvement correlated with diplopia at first observation, which was more severe in responders. A marked GO improvement correlated with time between first and last observation and time after thyroid treatment, which were longer in responders. This likely reflected the combination of an early effect of GC and a late, spontaneous improvement of GO, as shown by analyses of GO outcome at various time points. Additional treatments after ivGC correlated by multivariate analysis with eyelid aperture, diplopia and NOSPECS score (NOSPECS stands for no GO signs [N], only eyelid sign [O], soft tissue involvement [S], proptosis [P], extraocular motility restriction [E], corneal involvement [C], and sight loss [S]) at first observation, which were more severe in responders. CONCLUSION: Our study shows that response to ivGC increases with time, likely reflecting the known tendency of GO to improve spontaneously, and is more pronounced when GO is more severe to begin with, which is associated with more additional treatments. ABBREVIATIONS: ANOVA = analysis of variance CAS = clinical activity score GC = glucocorticoids GO = Graves orbitopathy 131I = radioactive iodine iv = intravenous ivGC = high-dose intravenous glucocorticoid pulse therapy MMI = methimazole OD = orbital decompression ORT = orbital radiotherapy TRAb = antithyroid-stimulating hormone receptor antibodies.
Assuntos
Glucocorticoides/administração & dosagem , Oftalmopatia de Graves/tratamento farmacológico , Metimazol/administração & dosagem , Administração Intravenosa , Adulto , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/radioterapia , Humanos , Masculino , Metimazol/efeitos adversos , Pessoa de Meia-Idade , Prognóstico , Pulsoterapia , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Growing evidence suggests that the intracorporeal fashioning of an anastomosis after a laparoscopic right colectomy may offer several advantages. However, due to the difficulty of the intracorporeal technique, laparoscopic extracorporeal confectioning of the anastomosis remains the most widely adopted technique. Although the purpose of the robotic approach was to overcome the limitations of the laparoscopic technique and to simplify the most demanding surgical procedures, such as performing an intracorporeal anastomosis, evidence is lacking that compares the robotic right colectomy with intracorporeal anastomosis (RRCIA) technique with both the conventional laparoscopic right colectomy with extracorporeal anastomosis (LRCEA) and the laparoscopic right colectomy with intracorporeal anastomosis confectioning (LRCIA) techniques. This study aims to compare the intraoperative and postoperative outcomes of the RRCIA to those of both the LRCEA and the LRCIA. METHODS: A retrospective review of a prospectively maintained database of two Italian centres was performed on the data on patients undergoing an RRCIA, LRCEA or LRCIA for cancer or adenomas. RESULTS: Two hundred and thirty-six patients (RRCIA = 102, LRCEA = 94, LRCIA = 40) met the criteria for inclusion in the study. The three groups were comparable in their demographic and baseline characteristics. No significant differences were found in the conversion to open rates, intraoperative blood loss, 30-day morbidity and mortality, number of lymphnodes harvested and other pathological characteristics. Compared with the LRCEA, the RRCIA required a longer operative time (P < 0.0001) but had better recovery outcomes, such as a shorter length of hospital stay (P < 0.0001). Compared with the LRCIA, the RRCIA had a shorter time to first flatus (P < 0.0001) but offered no advantages in terms of the length of the hospital stay. CONCLUSION: Performing the RRCIA offers significantly better perioperative recovery outcomes compared with the LRCEA, with a substantial reduction in the length of the hospital stay. The RRCIA does not offer the same advantages compared with the LRCIA.
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Colectomia/métodos , Colo/cirurgia , Neoplasias do Colo/cirurgia , Íleo/cirurgia , Laparoscopia/métodos , Robótica , Idoso , Anastomose Cirúrgica/métodos , Feminino , Humanos , Tempo de Internação/tendências , Masculino , Duração da Cirurgia , Estudos RetrospectivosRESUMO
OBJECTIVE: The Vps10p family member sortilin is expressed in thyroid epithelial cells where it contributes to recycling of the thyroid hormone precursor thyroglobulin (Tg), a process that is thought to render hormone release more effective. Here we investigated the functional impact of sortilin in the thyroid gland using sortilin-deficient mice. METHODS: We measured free T4, thyroid-stimulating hormone (TSH) and Tg serum levels and studied thyroid morphology in 14 sortilin-deficient (Sort1)(-/-)and 12 wildtype (WT) mice. RESULTS: Serum free T4 levels did not differ between Sort1(-/-)and WT females but were significantly lower in Sort1(-/-)males compared with WT (P = .0424). Neither serum TSH nor Tg levels differed between Sort1(-/-)and WT mice, regardless of sex. On the same line, no thyroid histology differences were observed. CONCLUSION: Our findings seem to exclude a role of sortilin in thyroid hormone secretion, although it is possible that the absence of sortilin may result in a thyroid phenotype if combined with other molecular defects of thyroid hormone synthesis and secretion or under iodine deficiency.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/deficiência , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Glândula Tireoide/fisiologia , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Tireoglobulina/sangue , Glândula Tireoide/anatomia & histologia , Glândula Tireoide/metabolismo , Tireotropina/sangue , Tiroxina/sangueRESUMO
Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), ß-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.
Assuntos
Antitireóideos/uso terapêutico , Doença de Graves/diagnóstico , Doença de Graves/tratamento farmacológico , Metimazol/uso terapêutico , Propiltiouracila/uso terapêutico , Animais , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Resultado do TratamentoRESUMO
Vascular tone regulation is a crucial aspect of cardiovascular physiology, with significant implications for overall cardiovascular health. However, the precise physiological mechanisms governing smooth muscle cell contraction and relaxation remain uncertain. The complexity of vascular tone regulation stems from its multiscale and multifactorial nature, involving global hemodynamics, local flow conditions, tissue mechanics, and biochemical pathways. Bridging this knowledge gap and translating it into clinical practice presents a challenge. In this paper, a computational model is presented to integrate chemo-mechano-biological pathways with cardiovascular biomechanics, aiming to unravel the intricacies of vascular tone regulation. The computational framework combines an algebraic description of global hemodynamics with detailed finite element analyses at the scale of vascular segments for describing their passive and active mechanical response, as well as the molecular transport problem linked with chemo-biological pathways triggered by wall shear stresses. Their coupling is accounted for by considering a two-way interaction. Specifically, the focus is on the role of nitric oxide-related molecular pathways, which play a critical role in modulating smooth muscle contraction and relaxation to maintain vascular tone. The computational framework is employed to examine the interplay between localized alterations in the biomechanical response of a specific vessel segment-such as those induced by calcifications or endothelial dysfunction-and the broader global hemodynamic conditions-both under basal and altered states. The proposed approach aims to advance our understanding of vascular tone regulation and its impact on cardiovascular health. By incorporating chemo-mechano-biological mechanisms into in silico models, this study allows us to investigate cardiovascular responses to multifactorial stimuli and incorporate the role of adaptive homeostasis in computational biomechanics frameworks.
Assuntos
Simulação por Computador , Análise de Elementos Finitos , Modelos Cardiovasculares , Fenômenos Biomecânicos , Humanos , Estresse Mecânico , Hemodinâmica/fisiologia , Óxido Nítrico/metabolismo , Mecanotransdução Celular/fisiologia , Vasos Sanguíneos/fisiologiaRESUMO
Graves disease is the most common cause of hyperthyroidism in iodine-sufficient areas. The main responsible mechanism is related to autoantibodies that bind and activate the thyrotropin receptor (TSHR). Although Graves hyperthyroidism is relatively common, no causal treatment options are available. Established treatment modalities are antithyroid drugs, which reduce thyroid hormone synthesis, radioactive iodine and surgery. However, emerging drugs that target the main autoantigen (monoclonal antibodies, small molecules, peptides) or block the immune pathway have been recently tested in clinical trials. Graves disease can involve the thyroid exclusively or it can be associated with extrathyroidal manifestations, among which Graves orbitopathy is the most common. The presence of Graves orbitopathy can change the management of the disease. An established treatment for moderate-to-severe Graves orbitopathy is intravenous glucocorticoids. However, recent advances in understanding the pathogenesis of Graves orbitopathy have allowed the development of new target-based therapies by blocking pro-inflammatory cytokine receptors, lymphocytic infiltration or the insulin-like growth factor 1 receptor (IGF1R), with several clinical trials providing promising results. This article reviews the new discoveries in the pathogenesis of Graves hyperthyroidism and Graves orbitopathy that offer several important tools in disease management.