Protocolo Clínico e Diretrizes Terapêuticas da miastenia gravis / Clinical Protocol and Therapeutic Guidelines for myasthenia gravis

CONTEXTO: Os PCDT são documentos que visam garantir o melhor cuidado de saúde diante do contexto brasileiro e dos recursos disponíveis no SUS. Podem ser utilizados como materiais educativos aos profissionais de saúde, auxílio administrativo aos gestores, regulamentação da conduta assistencial perante o Poder Judiciário e explicitação de direitos aos usuários do SUS. Os PCDT são os documentos oficiais do SUS que estabelecem critérios para o diagnóstico de uma doença ou agravo à saúde; tratamento preconizado, com os medicamentos e demais produtos apropriados, quando couber; posologias recomendadas; mecanismos de controle clínico; e acompanhamento e verificação dos resultados terapêuticos a serem seguidos pelos gestores do SUS. Os PCDT devem incluir recomendações de condutas, medicamentos ou produtos para as diferentes fases evolutivas da doença ou do agravo à saúde de que se tratam, bem como aqueles indicados em casos de perda de eficácia e de surgimento de intolerância ou reação adversa relevante, provocadas pelo medicamento, produto ou procedimento de primeira escolha. A lei reforçou a análise baseada em evidências científicas para a elaboração dos protocolos, destacando os critérios de eficácia, segurança, efetividade e custo-efetividade para a formulação das recomendações sobre intervenções em saúde. Para a constituição ou alteração dos PCDT, a Portaria GM n° 2.009 de 2012 instituiu na Conitec uma Subcomissão Técnica de Avaliação de PCDT, com as competências de definir os temas para novos protocolos, acompanhar sua elaboração, avaliar as recomendações propostas e as evidências científicas apresentadas, além da revisão periódica dos PCDT vigentes, em até dois anos. A Subcomissão Técnica de Avaliação de PCDT é composta por representantes de Secretarias do Ministério da Saúde interessadas na elaboração de diretrizes clínicas: Secretaria de Atenção Primária à Saúde, Secretaria de Atenção Especializada à Saúde, Secretaria de Vigilância em Saúde, Secretaria Especial de Saúde Indígena e Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde. Após concluídas as etapas de definição do tema e escopo do PCDT, de busca, seleção e análise de evidências científicas e consequente definição das recomendações, a aprovação do texto é submetida à apreciação do Plenário da Conitec, com posterior disponibilização deste documento para contribuição de sociedade, por meio de consulta pública (CP) pelo prazo de 20 dias, antes da deliberação final e publicação. A consulta pública é uma importante etapa de revisão externa dos PCDT. O Plenário da Conitec é o fórum responsável pelas recomendações sobre a constituição ou alteração de PCDT, além dos assuntos relativos à incorporação, exclusão ou alteração das tecnologias no âmbito do SUS, bem como sobre a atualização da Relação Nacional de Medicamentos Essenciais (RENAME). É composto por treze membros, um representante de cada Secretaria do Ministério da Saúde ­ sendo o indicado pela Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) o presidente do Plenário ­ e um representante de cada uma das seguintes instituições: ANVISA, Agência Nacional de Saúde Suplementar - ANS, Conselho Nacional de Saúde - CNS, Conselho Nacional de Secretários de Saúde - CONASS, Conselho Nacional de Secretarias Municipais de Saúde - CONASEMS e Conselho Federal de Medicina - CFM. Cabe à Secretaria-Executiva, exercida pelo Departamento de Gestão e Incorporação de Tecnologias e Inovação em Saúde (DGITIS/SCTIE), a gestão e a coordenação das atividades da Conitec. Conforme o Decreto n° 7.646 de 2011, o Secretário de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde deverá submeter o PCDT à manifestação do titular da Secretaria responsável pelo programa ou ação a ele relacionado antes da sua publicação e disponibilização à sociedade. APRESENTAÇÃO: A proposta de atualização do PCDT de Miastenia Gravis é uma demanda que cumpre o Decreto nº 7.508 de 28 de junho de 2011 e as orientações previstas no artigo 26º e o parágrafo único, sobre a responsabilidade do Ministério da Saúde de atualizar os Protocolos Clínicos e Diretrizes Terapêuticas. Este PCDT apresenta a atualização da versão publicada em 2015, com inclusão do exame complementar de diagnóstico dosagem sérica de anticorpos de acetilcolina (anti-AChR). DELIBERAÇÃO INICIAL: Os membros da Conitec presentes na 88ª Reunião do Plenário, realizada nos dias 07, 08 e 09 de julho de 2020, deliberaram para que o tema fosse submetido à consulta pública com recomendação preliminar favorável à publicação deste Protocolo. CONSULTA PÚBLICA: A Consulta Pública nº 27/2020 foi realizada entre os dias 21 de julho a 10 de agosto de 2020. A seguir é apresentado o resumo da análise das contribuições recebidas, ressaltando-se que foram consideradas apenas as encaminhadas no período estipulado e por meio do sítio eletrônico da Conitec. Os dadosforam avaliados quantitativa e qualitativamente, considerando asseguintes etapas: a) leitura de todas as contribuições, b) identificação e categorização das ideias centrais, e c) discussão acerca das contribuições. Foram recebidas ao todo 34 contribuições. A grande maioria dos participantes (n= 33; 97%) classificou a proposta de PCDT como boa ou muito boa na avaliação geral.

Modified Subxiphoid Thoracoscopic Thymectomy for Locally Invasive Thymoma.

BACKGROUND: We explored the feasibility and safety of modified subxiphoid thoracoscopic thymectomy for patients with locally invasive thymomas. METHODS: Subxiphoid thoracoscopic thymectomy was performed on select patients with locally invasive thymomas (Masaoka stage III) using an auxiliary sternal retractor to create a larger operative field. RESULTS: From June 2015 to March 2019, we performed modified subxiphoid thoracoscopic thymectomy on 48 patients with locally invasive thymomas: 39 patients had pericardium or lung infiltration and received a combination of a partial pericardium or lung wedge resection, and 9 patients had left innominate vein infiltration and underwent combined resection of the left innominate vein. Thoracoscopic thymectomy was performed from the subxiphoid pathway with an auxiliary sternal retractor in all 48 patients, and there were no conversions to median sternotomy. The median tumor size was 5 cm, and the maximal tumor size was 12 cm. The median blood loss was 50 mL. The median duration of chest tube placement was 3 days, and the median hospital stay was 4.5 days after surgery. All patients achieved a good recovery after surgery, and none had serious complications during the perioperative period. All patients underwent postoperative adjuvant radiotherapy and presented no local recurrence or distant metastasis until now. CONCLUSIONS: Modified subxiphoid thoracoscopic thymectomy with an auxiliary sternal retractor makes minimally invasive thymectomy easier and safer to perform and is an alternative approach for some patients with locally invasive thymomas.

Nonintubated Uniportal Thoracoscopic Thymectomy with Laryngeal Mask.

OBJECTIVE: To investigate whether laryngeal mask anesthesia had more favorable postoperative outcomes than double-lumen tube intubation anesthesia in uniportal thoracoscopic thymectomy. METHODS: Data were collected retrospectively from December 2013 to December 2017. A total of 96 patients with anterior mediastinum mass underwent nonintubated uniportal video-assisted thoracoscopic thymectomy with laryngeal mask, and 129 patients underwent intubated uniportal video-assisted thoracoscopic thymectomy. A single incision of ∼3 cm was made in an intercostal space along the anterior axillary line. Perioperative outcomes between nonintubated uniportal video-assisted thoracoscopic surgery (NU-VATS) and intubated uniportal video-assisted thoracoscopic surgery (IU-VATS) were compared. RESULTS: In both groups, incision size was kept to a minimum, with a median of 3 cm, and complete thymectomy was performed in all patients. Mean operative time was 61 minutes. The mean lowest SpO2 during operation was not significantly different. However, the mean peak end-tidal carbon dioxide in the NU-VATS group was higher than in the IU-VATS group. Mean chest tube duration in NU-VATS group was 1.9 days. Mean postoperative hospital stay was 2.5 days, with a range of 1 to 4 days. Time to oral fluid intake in the NU-VATS group was significantly less than in the IU-VATS group (p < 0.01). Several complications were significantly less in the NU-VATS group than in the IU-VATS group, including sore throat, nausea, irritable cough, and urinary retention. CONCLUSION: Compared with intubated approach, nonintubated uniportal thoracoscopic thymectomy with laryngeal mask is feasible for anterior mediastinum lesion, and patients recovered faster with less complications.

A Novel and Simple Method for Establishing the Subxiphoid Approach During Thoracoscopic Thymectomy.

The transsubxiphoid thoracoscopic approach is an ideal method for thoracoscopic thymectomy. This report introduces a simple method to establish the subxiphoid approach. The surgeon made an incision and inserted a homemade gasbag into the retrosternal space. The gasbag was inflated with 600 to 800 mL of air. The inflated gasbag was maintained for 5 minutes and removed. This technique was performed in 20 cases. This method provides the surgeon with a good field of view, rare thoracoscope contamination, and a smoother surgical procedure. Therefore, the method described in this study is a powerful option to establish the subxiphoid approach during thoracoscopic thymectomy.

Thymothymectomy with pulmonary partial resection using the subxiphoid approach: how to do it?

An open approach by sternotomy is still selected for locally advanced anterior mediastinal tumors. Technical and instrumental improvements to video-assisted thoracic surgery (VATS) have enabled the treatment of anterior mediastinal tumor in the last decade, and the indications of VATS for an anterior mediastinal tumor are thus expanding. Recently, a single-port thymectomy procedure using the subxiphoid approach has gained popularity worldwide because of its low invasiveness. Improvements to the thoracoscopic instruments and the development of a single-port device are expanding the adoption of single-port VATS in the thoracic surgical field, including resection of anterior mediastinal tumors. We, herein, report a case of thymothymectomy with pulmonary partial resection using the subxiphoid approach. This approach is useful for extended operation for anterior mediastinal tumors and provides favorable results regarding postoperative pain and cosmetic outcomes.

[Video-assisted thoracoscopic thymectomy in myasthenia gravis. New approach]. / Videoassistirovannaia torakoskopicheskaia timéktomiia pri miastenii. Novyi podkhod.

AIM: To present possibility and technical aspects of anesthetic management during video-assisted thoracoscopic thymectomy in patients with myasthenia gravis. MATERIAL AND METHODS: The article describes the proposed modified anesthetic method that is suitable for video-assisted thoracoscopic thymectomy in patients with myasthenia gravis. Nine patients with myasthenia underwent VATS-thymectomy. Anesthesia was performed with artificial airway and auxiliary ventilation without muscle relaxants administration.

Robotic Resection of 3 cm and Larger Thymomas Is Associated With Low Perioperative Morbidity and Mortality.

OBJECTIVE: The approach to thymoma resection has usually been determined by tumor size, although established guidelines do not exist. Minimally invasive approaches have been limited to tumors smaller than 5 cm, although 3 cm has been the suggested cutoff for performing an adequate oncologic procedure. No study has compared the perioperative outcomes of patients with 3 cm or larger tumors resected robotically versus sternotomy. METHODS: We reviewed patients who underwent resection of 3 cm or larger thymomas from 2004 to 2014. Patients were divided based on approach: robotic and open thymectomy/thymomectomy. RESULTS: Forty patients with tumors ranging from 3 to 13 cm were evaluated, 23 robotic and 17 open. Patient and tumor characteristics were similar. An R0 resection was primarily achieved: robotic, 91% (21/23); and open, 88% (15/17); P = 0.832. Adjuvant radiation rates were statistically equivalent: robotic, 17% (4/23) versus open, 41% (7/17); P = 0.191. Major postoperative complications were comparable: robotic, 4% (1/23) versus open, 29% (4/17); P = 0.184. Median chest tube duration was shorter for robotic (1 day) versus open (3 days); P = 0.001. The robotic approach had a shorter median intensive care unit stay compared to open (0 days vs 1 day); P = 0.024. The median hospital stay was shorter for robotic (2 days) versus open (5 days); P < 0.001. CONCLUSIONS: In 3 cm or larger thymomas, robotic thymectomy is feasible based on the ability to achieve a complete resection with similar adjuvant radiation therapy rates. Perioperatively, robotic thymectomy is associated with lower morbidity; and shorter chest tube duration, intensive care unit stay, and hospital stay compared to open. However, oncologic outcomes are immature and require prolonged surveillance.

Minimally invasive anterior chest wall lifting technique for thoracoscopic mediastinal approach.

Anterior chest wall lifting facilitates a wide view and allows easy access during thoracoscopic surgery in a supine position for anterior mediastinal lesions. We previously reported an anterior chest wall lifting method for a thymectomy that utilizes our original costal hooks. Here, we present a less invasive method that can be performed with only a needle puncture, i.e., a metal plate placed under the ribs is lifted with a wire inserted through the anterior chest wall. We have applied this novel 'T-lifting method' for 5 different cases with anterior mediastinal tumors, and found it to be simple and easy to perform, as well as less invasive for patients undergoing thoracoscopic surgery.

Timectomía transesternal ampliada en forma de alas de mariposa / "Butterfly wings" shape maximal trans sternal thymectomy

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[Application of the da Vinci robotic system in thoracic surgery]. / Anwendung des daVinci-Robotersystems in der Thoraxchirurgie.

INTRODUCTION: The latest technical developments of minimally invasive thoracic surgery are characterized by robotic-assisted operative procedures. Robotic-assisted thymectomy is the most advanced method in this field. METHODS: A systematic literature search (PubMed, Medline) was carried out and the databank system of Intuitive Surgical (Sunnyvale, CA) was analysed. Target criteria were the analysis of the quantitative data over time, technical advantages and limiting factors of robotic-assisted thoracic surgery. RESULTS: The da Vinci robotic system has been used in thoracic surgery since 2001, and up to 2012 a total of 10,895 robotic-assisted lobotomies have been carried out worldwide. A total of 12 ectopic parathyroid glands in the mediastinum were resected and published. Furthermore, more than 3,500 cases of robotic-assisted thymectomy were performed. A rapid increase in the number of operations has occurred particularly for thymectomy and lung resections. DISCUSSION: Acceptance of robotic-assisted thymectomy for myasthenia and/or thymoma and mediastinal tumors is growing rapidly. For anatomic lung resection in lung cancer, robotic-assisted hilar and lymph node dissection due to this new quality are also comparable to open surgical techniques. The principles form the intrinsic technical advantages of the da Vinci robotic system.

Novel use of the internal thoracic artery retractor in transcervical thymectomy.

Transcervical thymectomy is a standard approach to the thymus and anterior mediastinum, but it is limited by poor exposure of the lower recesses of the anterior mediastinum. A novel technique using the widely available internal thoracic artery sternal retractor and a 30°-video camera allows enhanced exposure of the anterior mediastinum.

Long-term effects of infrasternal mediastinoscopic thymectomy in myasthenia gravis.

BACKGROUND: Endoscopic thymectomy is commonly used for treatment of myasthenia gravis (MG) patients due to its relatively low invasiveness. However, the long-term effects of endoscopic thymectomy have not been fully evaluated. OBJECTIVE: To assess the long-term effects of extended infrasternal mediastinoscopic thymectomy (IMT) in MG patients and compare them with those of extended transsternal thymectomy (TT). METHODS: Among 24 MG patients without thymoma who underwent thymectomy in our Institute between January 1997 and December 2000, 14 patients who received IMT and 10 who received TT were enrolled in the present study. Quantitative myasthenia gravis (QMG) score and anti-acetylcholine receptor antibody (anti-AChR) titers were evaluated before and at five years after surgery. RESULTS: After five years, QMG scores were reduced from 6.6 to 1.8 (p<0.01) in the IMT group, and from 7.6 to 2.7 (p<0.01) in the TT group. The anti-AChR titers were reduced from 75.2 to 40.1 (p=0.027) in the IMT group, and from 224 to 61.3 (p=0.020) in the TT group. CONCLUSION: These data suggest that the long-term therapeutic effect of IMT is equivalent to TT, and is thus suitable for the treatment of MG patients.

Advancing neurosurgery with image-guided robotics.

Robotic systems are being introduced into surgery to extend human ability. NeuroArm represents a potential change in the way surgery is performed; this is the first image-guided, MR-compatible surgical robot capable of both microsurgery and stereotaxy. This paper presents the first surgical application of neuroArm in an investigation of microsurgical performance, navigation accuracy, and Phase I clinical studies. To evaluate microsurgical performance, 2 surgeons performed microsurgery (splenectomy, bilateral nephrectomy, and thymectomy) in a rodent model using neuroArm and conventional techniques. Two senior residents served as controls, using the conventional technique only (8 rats were used in each of the 3 treatment groups; the 2 surgeons each treated 4 rats from each group). Total surgery time, blood loss, thermal injury, vascular injury, and animal death due to surgical error were recorded and converted to an overall performance score. All values are reported as the mean +/- SEM when normally distributed and as the median and interquartile range when not. Surgeons were slower using neuroArm (1047 +/- 69 seconds) than with conventional microsurgical techniques (814 +/- 54 seconds; p = 0.019), but overall performance was equal (neuroArm: 1110 +/- 82 seconds; microsurgery: 1075 +/- 136 seconds; p = 0.825). Using microsurgery, the surgeons had overall performance scores equal to those of the control resident surgeons (p = 0.141). To evaluate navigation accuracy, the localization error of neuroArm was compared with an established system. Nanoparticles were implanted at predetermined bilateral targets in a cadaveric model (4 specimens) using image guidance. The mean localization error of neuroArm (4.35 +/- 1.68 mm) proved equal to that of the conventional navigation system (10.4 +/- 2.79 mm; p = 0.104). Using the conventional system, the surgeon was forced to retract the biopsy tool to correct the angle of entry in 2 of 4 trials. To evaluate Phase I clinical integration, the role of neuroArm was progressively increased in 5 neurosurgical procedures. The impacts of neuroArm on operating room (OR) staff, hardware, software, and registration system performance were evaluated. NeuroArm was well received by OR staff and progressively integrated into patient cases, starting with draping in Case 1. In Case 2 and all subsequent cases, the robot was registered. It was used for tumor resection in Cases 3-5. Three incidents involving restrictive cable length, constrictive draping, and reregistration failure were resolved. In Case 5, the neuroArm safety system successfully mitigated a hardware failure. NeuroArm performs as well and as accurately as conventional techniques, with demonstrated safety technology. Clinical integration was well received by OR staff, and successful tumor resection validates the surgical applicability of neuroArm.

National survey of endoscopic thymectomy: survey report from the Japanese Association for Research on the Thymus.

Currently, no specific item regarding endoscopic thymectomy for nonthymomatous myasthenia gravis is listed in the standards of deciding medical service fees. To understand the present situation regarding the medical fee-for-service for endoscopic thymectomy, a questionnaire survey was conducted involving the institutions and members participating in the Japanese Association for Research on the Thymus. Of 101 responding institutions, 18 (18%) reported basically performing endoscopic thymectomy in all qualifying patients, and 32% of the institutions reported mainly performing median sternotomy but sometimes performing endoscopic thymectomy. The methods of approaching endoscopic thymectomy varied among the institutions, but most included endoscopic clips or ultrasound-driven scalpels as well as anterior chest wall lifting devices. A total of 214 patients underwent thymectomy in 2004 in the responding institutions, of whom 77 patients (32%) underwent endoscopic thymectomy. In total, 71% of the responding institutions answered that a specific item regarding endoscopic thymectomy should be listed in the standards for deciding medical service fees.

Harmonic scalpel in video-assisted thoracoscopic thymic resections.

Video-assisted thoracoscopic thymectomy is safe, but the efficacy of this technique in thymomectomy is unproved. Data of 103 consecutive patients who had thoracoscopic thymectomy and thymomectomy between 1998 and 2006 were retrospectively reviewed. Conventional monopolar diathermy and endoscopic Liga clips were used in the first 50 patients, and the Harmonic Scalpel was employed in the next 53. Only mean tumor size differed between groups (56.6 +/- 18.2 vs 40.0 +/- 20.8 mm in Harmonic Scalpel group). A similar number of patients had myasthenia gravis in the first group (72%) and Harmonic Scalpel group (83%). There were 49 thymomas (22 in first group, 27 in Harmonic Scalpel group). Of the earlier patients, 2 were re-explored for excessive chest tube drainage, 1 had ipsilateral phrenic nerve injury, and 2 had left phrenic nerves sacrificed intraoperatively due to thymoma invasion, but there was no significant difference in complications between groups. At a mean follow-up of 3.40 +/- 2.38 years (range, 0.04-8.52 years), there was 1 thymoma recurrence in the first group. Use of the Harmonic Scalpel in video-assisted thoracoscopic thymic resection is safe and confers some advantages over conventional methods of dissection.

Early experience with robot-assisted surgery for mediastinal masses.

BACKGROUND: We report the experience of a single institution with the minimally invasive resection of mediastinal masses using the da Vinci robotic surgical system. METHODS: From August 2001 to June 2003, 14 patients (5 men and 9 women aged from 21 to 77 years) with mediastinal masses were operated on minimally invasively with the da Vinci robotic system. This consisted of 9 thymectomies (6 thymomas, 2 nonatrophic thymic glands, 1 thymic cyst), 3 resections of paravertebral neurinomas, 1 ectopic mediastinal parathyroidectomy, and 1 resection of a lymphangioma. RESULTS: Complete, extended thymectomy was accomplished in all 9 cases, proven by examination of the thymic bed and resected specimen. In 1 patient with an hourglass-shaped neurinoma, conversion to an open procedure was necessary because the excessive size of the tumor limited vision. The median overall operation time was 166 minutes (range, 61 to 182) including 110 minutes (range, 46 to 142) for the robotic act. There were no intraoperative complications or surgical mortality. CONCLUSIONS: These preliminary results of our series suggest that application of the da Vinci robotic surgical system for resection of selected mediastinal masses is technically feasible and safe. It provides an alternative to open approaches and "conventional" thoracoscopy. Nevertheless, this new technique requires further investigation in larger series and longer follow-up.