RESUMO
BACKGROUND: Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete. OBJECTIVES: To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis. SEARCH METHODS: We identified studies through systematic searches of the following bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); and Embase from January 1947 to December 2020. In addition, we checked trial registries for ongoing or unpublished eligible trials and manually searched for abstracts from scientific and clinical meetings. SELECTION CRITERIA: We evaluated randomised controlled trials (RCTs) comparing two or more therapies in people with NETs (primarily gastrointestinal and pancreatic). DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data to a pre-designed data extraction form. Multi-arm studies were included in the network meta-analysis using the R-package netmeta. We separately analysed two different outcomes (disease control and progression-free survival) and two types of NET (gastrointestinal and pancreatic NET) in four network meta-analyses. A frequentist approach was used to compare the efficacy of therapies. MAIN RESULTS: We identified 55 studies in 90 records in the qualitative analysis, reporting 39 primary RCTs and 16 subgroup analyses. We included 22 RCTs, with 4299 participants, that reported disease control and/or progression-free survival in the network meta-analysis. Precision-of-treatment estimates and estimated heterogeneity were limited, although the risk of bias was predominantly low. The network meta-analysis of progression-free survival found nine therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.36 [95% CI, 0.28 to 0.46]), interferon plus somatostatin analogue (HR, 0.34 [95% CI, 0.14 to 0.80]), everolimus plus somatostatin analogue (HR, 0.38 [95% CI, 0.26 to 0.57]), bevacizumab plus somatostatin analogue (HR, 0.36 [95% CI, 0.15 to 0.89]), interferon (HR, 0.41 [95% CI, 0.18 to 0.94]), sunitinib (HR, 0.42 [95% CI, 0.26 to 0.67]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.48 [95% CI, 0.28 to 0.83]), surufatinib (HR, 0.49 [95% CI, 0.32 to 0.76]), and somatostatin analogue (HR, 0.51 [95% CI, 0.34 to 0.77]); and six therapies for gastrointestinal NETs: 177-Lu-DOTATATE plus somatostatin analogue (HR, 0.07 [95% CI, 0.02 to 0.26]), everolimus plus somatostatin analogue (HR, 0.12 [95%CI, 0.03 to 0.54]), bevacizumab plus somatostatin analogue (HR, 0.18 [95% CI, 0.04 to 0.94]), interferon plus somatostatin analogue (HR, 0.23 [95% CI, 0.06 to 0.93]), surufatinib (HR, 0.33 [95%CI, 0.12 to 0.88]), and somatostatin analogue (HR, 0.34 [95% CI, 0.16 to 0.76]), with higher efficacy than placebo. Besides everolimus for pancreatic NETs, the results suggested an overall superiority of combination therapies, including somatostatin analogues. The results indicate that NET therapies have a broad range of risk for adverse events and effects on quality of life, but these were reported inconsistently. Evidence from this network meta-analysis (and underlying RCTs) does not support any particular therapy (or combinations of therapies) with respect to patient-centred outcomes (e.g. overall survival and quality of life). AUTHORS' CONCLUSIONS: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.
Assuntos
Neoplasias Pancreáticas , Sulfonamidas , Humanos , Indóis , Metanálise em Rede , Neoplasias Pancreáticas/tratamento farmacológico , Tomografia por Emissão de Pósitrons , Pirimidinas , CintilografiaRESUMO
BACKGROUND: High-volume caseload in thyroid surgery is associated with lower postoperative complication rates resulting to better outcomes. The aim of the present study was to investigate the correlation of the departments' annual number of thyroid surgeries on the adherence to consensus guidelines and on the implementation of measures for quality assurance. METHODS: In 2016, we sent an anonymous electronic survey with questions related to the perioperative management in thyroid surgery to all directors of departments in operative medicine in Switzerland and Austria. We compared the pre- and postoperative management with the summarized recommendations of the four most frequently used consensus guidelines. Analogously, we analyzed the implementation of six measures for quality assurance related to thyroid surgery for each participating department. Using logistic regression analysis, we evaluated the correlation of number of guidelines respected and number of measures for quality assurance with the departments' annual number of surgeries performed. Furthermore, we evaluated the number of departments providing thyroid cancer surgery and their experience in neck dissection. RESULTS: The management corresponded in 64.0% to the summarized recommendations. Adherence to the summarized recommendations and implementation of measures for quality assurance were significantly more likely with increasing numbers of surgeries performed (p = 0.049 and p < 0.001). Ninety-two departments provided thyroid cancer surgery, whereas 12/92 (13.0%) were not able to perform central and/or lateral neck dissection. CONCLUSION: Consensus guidelines are insufficiently implemented within thyroid surgery, and quality management is associated with surgical volume.
Assuntos
Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Garantia da Qualidade dos Cuidados de Saúde , Neoplasias da Glândula Tireoide/cirurgia , Humanos , Modelos Logísticos , Esvaziamento Cervical , Complicações Pós-Operatórias/epidemiologia , Guias de Prática Clínica como AssuntoRESUMO
OBJECTIVE: Little is known about the natural changes in parathyroid function after successful parathyroid surgery for primary hyperparathyroidism. The association of intact parathyroid hormone (iPTH) and calcium (Ca) with "temporary hypoparathyroidism" and "hungry bone syndrome" (HBS) was evaluated. DESIGN: Potential risk factors for temporary hypoparathyroidism and HBS were evaluated by taking blood samples before surgery, intra-operatively, at postoperative day (POD) 1, at POD 5 to 7, in postoperative week (POW) 8 and in postoperative month (POM) 6. PATIENTS: Of 425 patients, 43 (10.1%) had temporary hypoparathyroidism and 36 (8.5%) had HBS. MEASUREMENTS: The discriminative ability of iPTH and Ca on POD 1 for temporary hypoparathyroidism and HBS. RESULTS: Intact parathyroid hormone (IPTH) on POD 1 showed the highest discriminative ability for temporary hypoparathyroidism (C-index = 0.952), but not for HBS. IPTH was helpful in diagnosing HBS between POD 5 and 7 (C-index = 0.708). Extending the model by including Ca resulted in little improvement of the discriminative ability for temporary hypoparathyroidism (C-index = 0.964) and a decreased discriminative ability for HBS (C-index = 0.705). Normal parathyroid metabolism was documented in 139 (32.7%) patients on POD 1 and in 423 (99.5%) 6 months postoperatively, while 2 (0.5%) patients had persistent hyperparathyroidism, one diagnosed between POD 5 and 7 and another at POW 8. No patients suffered from permanent hypoparathyroidism. CONCLUSIONS: The necessity for Ca and vitamin D3 substitution cannot be predicted with certainty before POD 5 to 7 without serial laboratory measurements. Based on the results, a routine 8-week course of Ca and vitamin D3 treatment seems reasonable and its necessity should be evaluated in a follow-up study.
Assuntos
Hiperparatireoidismo Primário/metabolismo , Glândulas Paratireoides/metabolismo , Período Pós-Operatório , Adulto , Cálcio/sangue , Cálcio/uso terapêutico , Feminino , Humanos , Hiperparatireoidismo Primário/cirurgia , Hipoparatireoidismo , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fatores de Risco , Fatores de Tempo , Vitamina D/uso terapêuticoRESUMO
BACKGROUND: It is of major importance in clinical surgery to identify potential patterns and specific causes of complications. Therefore, morbidity and mortality meetings (M&M) are widely used to discuss and evaluate deviations from expected outcomes in order to improve surgical practice. Moreover, M&M represent an important tool for continuous medical education. In this study, we introduced an electronic voting system to assess whether anonymity during M&M could limit potential biases due to hierarchical structures or opinion leaders. METHODS: This study was conducted in the surgical department of a European tertiary care center. During the study period, electronic voting was applied in 412 M&M cases and compared with a baseline of 330 conventional M&M entries. In this interrupted time series, the educational quality and participant satisfaction of the M&M were assessed using surveys before and after the introduction of electronic voting. The surveys were refined using principle component analysis. In addition, the classification of the cause of the complication was recorded. RESULTS: The introduction of electronic voting led to a significant increase in perceived educational quality from 2.63 to 3.36 (p < 0.01), and the overall participant satisfaction increased from 2.6 ± 0.9 to 3.7 ± 1.2 (p < 0.01) on a five-point Likert scale. The frequency of voting shifted from "patient's disease" (before 42.9, after 27.6%, p = 0.04) to "misadventure" (before 1.1, after 16.0%, p < 0.01). The voting frequencies for the causes attributed to "management" and "technical" remained constant. CONCLUSIONS: An electronic voting system in M&M meetings increases perceived educational quality and participant satisfaction.
Assuntos
Privacidade , Melhoria de Qualidade , Procedimentos Cirúrgicos Operatórios , Visitas de Preceptoria , Viés , Europa (Continente) , Docentes de Medicina , Feminino , Humanos , Internato e Residência , Análise de Séries Temporais Interrompida , Masculino , Qualidade da Assistência à Saúde , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Normal or elevated 24-hour urinary calcium (Ca) excretion is a diagnostic marker in primary hyperparathyroidism (PHPT). It is used to distinguish familial hypocalciuric hypercalcaemia (FHH) from PHPT by calculating the Ca/creatinine clearance ratio (CCCR). The variance of CCCR in patients with PHPT is considerable. The aim of this study was to analyse the parameters affecting CCCR in patients with PHPT. DESIGN: The data were collected prospectively. Patients with sporadic PHPT undergoing successful surgery were included in a retrospective analysis. PATIENTS: The analysis covered 381 patients with pre-operative workup 2 days before removal of a solitary parathyroid adenoma. MEASUREMENTS: The impact of serum Ca and 25-hydroxyvitamin D3 (25-OH D3) on CCCR. RESULTS: The coefficient of determination (R2 ) in the multivariable model for CCCR consisting of age, Ca, 25-OH D3, 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), testosterone (separately for males and females), intact parathyroid hormone (iPTH) and osteocalcin was 25.8%. The only significant parameters in the multivariable analysis were 1,25-(OH)2 D3 and osteocalcin with a drop in R2 of 15.4% (P<.001) and 2.4% (P=.006), respectively. Bone mineral densities at the lumbar spine, distal radius and left femoral neck were not associated with CCCR (r=-.08, r=-.10 and r=-0.09). CONCLUSIONS: In multivariable analysis, 1,25-(OH)2 D3 and osteocalcin were the only factors correlating with CCCR. Vitamin D3 replacement may therefore impair the diagnostic value of CCCR and increase the importance of close monitoring of urinary Ca excretion during treatment.
Assuntos
Cálcio/urina , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/urina , Idoso , Creatinina/urina , Diagnóstico Diferencial , Feminino , Humanos , Hipercalcemia/congênito , Hipercalcemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Neoplasias das Paratireoides/cirurgia , Período Pré-Operatório , Estudos Retrospectivos , Vitamina D/análogos & derivados , Vitamina D/sangueRESUMO
PURPOSE: Minimal access thyroidectomy, using various techniques, is widely known, but respective data on thyroidectomy for thyroid cancer with lymphadenectomy is scarce. The present study aims to evaluate the feasability of extended subplatysmal dissection in combination with a small incision ("mobile window" technique). METHODS: A retrospective study was performed analysing data from 93 patients. All patients suffered from thyroid carcinoma and underwent (total) thyroidectomy, bilateral cervico-central (levels VI and VII) and functional lateral neck dissection (levels II to V) on the side of the malignancy. In group A, consisting of 47 patients, the operation was performed by a traditional Kocher incision (minimal range 6-7 cm), in 46 patients (group B) a mini-incision (≤4 cm) was made. Intra- and postoperative morbidity as well as oncological accuracy were assessed. RESULTS: There was no significant difference between the two groups comparing postoperative pathological diagnosis, intra- and postoperative complications and the number of removed lymph nodes. However, operating time was slightly longer in group A and thyroid weight was heavier in group B. CONCLUSIONS: Extended subplatymsal dissection allows thyroidectomy and even lateral lymphadenectomy for thyroid carcinoma via "mobile" mini-incision. The procedure is safe, of equivalent oncological accuracy compared to traditional incision and the cosmetic results are excellent.
Assuntos
Carcinoma/cirurgia , Excisão de Linfonodo/métodos , Esvaziamento Cervical/métodos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Carcinoma/patologia , Dissecação/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Duração da Cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Adulto JovemRESUMO
OBJECTIVES: Preoperative and intraoperative diagnostic tools influence the surgical management of primary hyperparathyroidism (PHPT), whereby their performance of classification varies considerably for the two common causes of PHPT: solitary adenomas and multiglandular disease. A consensus on the use of such diagnostic tools for optimal perioperative management of all PHPT patients has not been reached. DESIGN: A decision tree model was constructed to estimate and compare the clinical outcomes and the cost-effectiveness of preoperative imaging modalities and intraoperative parathyroid hormone (ioPTH) monitoring criteria in a 21-year time horizon with a 3% discount rate. The robustness of the model was assessed by conducting a one-way sensitivity analysis and probabilistic uncertainty analysis. SETTING: The US healthcare system. POPULATION: A hypothetical population consisting of 5000 patients with sporadic, symptomatic or asymptomatic PHPT. INTERVENTIONS: Preoperative and intraoperative diagnostic modalities for parathyroidectomy. MAIN OUTCOME MEASURES: Costs, quality-adjusted life-years (QALYs), net monetary benefits (NMBs) and clinical outcomes. RESULTS: In the base-case analysis, four-dimensional (4D) CT was the least expensive strategy with US$10 276 and 15.333 QALYs. Ultrasound and 99mTc-Sestamibi single-photon-emission CT/CT were both dominated strategies while 18F-fluorocholine positron emission tomography was cost-effective with an NMB of US$416 considering a willingness to pay a threshold of US$95 958. The application of ioPTH monitoring with the Vienna criterion decreased the rate of reoperations from 10.50 to 0.58 per 1000 patients compared to not using ioPTH monitoring. Due to an increased rate of bilateral neck explorations from 257.45 to 347.45 per 1000 patients, it was not cost-effective. CONCLUSIONS: 4D-CT is the most cost-effective modality for the preoperative localisation of solitary parathyroid adenomas and multiglandular disease. The use of ioPTH monitoring is not cost-effective, but to minimise clinical complications, the Miami criterion should be applied for suspected solitary adenomas and the Vienna criterion for multiglandular disease.
Assuntos
Análise Custo-Benefício , Árvores de Decisões , Hiperparatireoidismo Primário , Paratireoidectomia , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Paratireoidectomia/economia , Hiperparatireoidismo Primário/cirurgia , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/economia , Técnicas de Apoio para a Decisão , Hormônio Paratireóideo/sangue , Tomografia Computadorizada Quadridimensional , Neoplasias das Paratireoides/cirurgia , Neoplasias das Paratireoides/diagnóstico , Resultado do TratamentoRESUMO
Resecting a large goiter extending into the retrosternal space is challenging, especially when a sternotomy or thoracotomy is required. The transthoracic approach is linked to higher postoperative morbidity, reaching up to 30% when compared to the transcervical approach. Although alternative options like thoracoscopic resection have shown promising results, the morbidity of mediastinal dissection remains a concern. Thoracoscopic-assisted transcervical approach might be a feasible, less invasive alternative. This video outlines the steps and potential pitfalls of the procedure. The patient is positioned supine with an extended neck. Initially, the endocrine surgeon mobilizes the thyroid gland through cervical access. If a transcervical resection is not feasible, the patient is mobilized into a lateral decubitus position, and a second team thoracoscopically guides the mediastinal tumor through the thoracic inlet. This allows a stepwise controlled transcervical dissection of the retrosternal mass until complete resection is achieved, thus eliminating the need for mediastinal dissection. To demonstrate the procedure, we present the case of an 84-year-old male with lymph node-positive oncocytic thyroid carcinoma and a large retrosternal goiter extending posteriorly into the mediastinum up to the aortic arch. Thoracoscopic-assisted transcervical resection was performed. The recurrent laryngeal nerve was identified and monitored with a neurostimulation device during dissection. No palsy was noted in the postoperative evaluation. The patient had an uneventful postoperative course and was discharged on the second postoperative day. Thoracoscopic-assisted transcervical resection of large retrosternal goiter seems a feasible alternative to mitigate risks associated with thoracotomy, sternotomy, or thoracoscopic mediastinal dissection. Potential advantages include decreased postoperative morbidity and length of stay. This technique requires thoracoscopic expertise and may be limited depending on the goiter's size and mediastinal positioning.
Assuntos
Bócio Subesternal , Humanos , Masculino , Idoso de 80 Anos ou mais , Bócio Subesternal/cirurgia , Bócio Subesternal/diagnóstico por imagem , Cirurgia Torácica Vídeoassistida/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologiaRESUMO
The calcium sensing receptor (CaSR) is a ubiquitously expressed G-protein coupled receptor (GPCR) that regulates extracellular calcium signals via the parathyroid glands. CaSR has recently also been implicated in noncalcitropic pathophysiologies like asthma, gut inflammation, and cancer. To date, molecular tools that enable the bioimaging of CaSR in tissues are lacking. Based on in silico analyses of available structure-activity relationship data on CaSR ligands, we designed and prepared silicon-rhodamine (SiR) conjugates of the clinically approved drug evocalcet. The new probes EvoSiR4 and EvoSiR6, with differing linker lengths at the evocalcet carboxyl end, both showed a 6-fold and 3-fold increase in potency toward CaSR (EC50 < 45 nM) compared to evocalcet and the evocalcet-linker conjugate, respectively, in an FLIPR-based cellular functional assay. The specificity of the EvoSiR probes toward CaSR binding and the impact of albumin was evaluated in live cell experiments. Both probes showed strong albumin binding, which facilitated the clearance of nonspecific binding interactions. Accordingly, in zebrafish embryos, EvoSiR4 specifically labeled the high CaSR expressing neuromasts of the lateral line in vivo. EvoSiR4 was also assessed in human parathyroid tissues ex vivo, showing a specific absolute CaSR-associated fluorescence compared to that of parathyroid autofluorescence. In summary, functionalization of evocalcet by SiR led to the preparation of potent and specific fluorescent CaSR probes. EvoSiR4 is a versatile small-molecular probe that can be employed in CaSR-related biomedical analyses where antibodies are not applicable.
RESUMO
Primary hyperparathyroidism with parathyroid tumors is a typical manifestation of Multiple Endocrine Neoplasia Type 1 (MEN1) and is historically termed "primary hyperplasia". Whether these tumors represent a multi-glandular clonal disease or hyperplasia has not been robustly proven so far. Loss of Menin protein expression is associated with inactivation of both alleles and a good surrogate for a MEN1 gene mutation. The cyclin-dependent kinase inhibitor 1B (CDKN1B) gene is mutated in MEN4 and encodes for protein p27 whose expression is poorly studied in the syndromic MEN1 setting.Here, we analyzed histomorphology and protein expression of Menin and p27 in parathyroid adenomas of 25 patients of two independent, well-characterized MEN1 cohorts. The pattern of loss of heterozygosity (LOH) was assessed by fluorescence in situ hybridization (FISH) in one MEN1-associated parathyroid adenoma. Further, next-generation sequencing (NGS) was performed on eleven nodules of four MEN1 patients.Morphologically, the majority of MEN1 adenomas consisted of multiple distinct nodules, in which Menin expression was mostly lost and p27 protein expression reduced. FISH analysis revealed that most nodules exhibited MEN1 loss, with or without the loss of centromere 11. NGS demonstrated both subclonal evolution and the existence of clonally unrelated tumors.Syndromic MEN1 parathyroid adenomas therefore consist of multiple clones with subclones, which supports the current concept of the novel WHO classification of parathyroid tumors (2022). p27 expression was lost in a large fraction of MEN1 parathyroids and must therefore be used with caution in suggesting MEN4.
Assuntos
Adenoma , Inibidor de Quinase Dependente de Ciclina p27 , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias das Paratireoides , Proteínas Proto-Oncogênicas , Humanos , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/genética , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/patologia , Masculino , Proteínas Proto-Oncogênicas/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Pessoa de Meia-Idade , Feminino , Adulto , Adenoma/patologia , Adenoma/genética , Idoso , Perda de Heterozigosidade , Hiperparatireoidismo Primário/patologia , Hiperparatireoidismo Primário/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Adulto Jovem , Sequenciamento de Nucleotídeos em Larga Escala , Hibridização in Situ FluorescenteRESUMO
Introduction: Students frequently rely on part-time jobs to earn a living wage. We sought to evaluate the sociodemographic status of Swiss medical students and their perception regarding equal career opportunities in view of impaired part-time job opportunities under the COVID-19 pandemic. Methods: We conducted an anonymous online survey among Swiss medical students from Bern and Geneva over a period of 4 months between December 2020 and April 2021. We evaluated sociodemographic data, current living situation, part-time job occupation as well as other sources of income to fund living expenses, and, by means of a five-point Likert scale (1=strongly disagree and 5=strongly agree), whether COVID-19 was perceived as impeding equal career opportunities. Results: Of 968 participants, corresponding to around 13.8% of all medical students in Switzerland, 81.3% had part-time jobs. Amongst the employed, 54.8% worked to afford living expenses and 28.9% reported a negative financial impact due to reduced part-time jobs under the pandemic. The loss of part-time jobs was perceived to make medical studies a privilege for students with higher socioeconomic status (4.11±1.0), whose opportunity to study is independent of a regular income. A governmental backup plan was considered crucial to support affected students (4.22±0.91). Discussion: COVID-19 and its sequelae are perceived as a threat for Swiss medical students and lead to a disadvantage for those with lower socioeconomic status. Nationwide measures should be established to foster equal career opportunities.
Assuntos
COVID-19 , Estudantes de Medicina , Humanos , Estudos Transversais , Suíça/epidemiologia , Pandemias , Escolha da Profissão , COVID-19/epidemiologia , OcupaçõesRESUMO
Introduction: The treatment of choice for retrosternal goiters (RSG) is surgical resection to relieve symptoms and rule out malignancy. Although the majority of RSG can be removed by a cervical approach only, an extracervical approach (e.g., sternotomy, thoracotomy or thoracoscopy) may be required. Herein, we describe a refined thoracoscopic-assisted cervical two-team RSG resection without thoracoscopic mediastinal dissection. Technique: A 57-year-old man presented with a large RSG with posterior mediastinal extension (PME) and extensive peritumoral vascularization. Due to its extension below the aortic arch and its small connection with the right thyroid lobe, a combined cervical and thoracoscopic approach was intended. The endocrine surgery unit performed the cervical mobilization of the right thyroid lobe, while the thoracic surgery unit gently pushed the mediastinal tumor through the thoracic inlet without performing mediastinal dissection. This allowed a safe visualization of the inserting vessels by the endocrine surgery team at the neck, followed by a stepwise division of the vessels and resection of the retrosternal nodule through the cervical access. Comment: The described approach is indicated for RSG with posterior mediastinal extension, anteroposterior dimension smaller than the thoracic inlet and inaccessibility from a cervical approach only. This minimally invasive approach is associated with a faster recovery, decreased morbidity and postoperative pain, shorter hospital stay and better cosmetic results.
RESUMO
IMPORTANCE: Multiple therapies are currently available for patients with neuroendocrine tumors (NETs), yet many therapies have not been compared head-to-head within randomized clinical trials (RCTs). OBJECTIVE: To assess the relative safety and efficacy of therapies for NETs. DATA SOURCES: PubMed, Embase, the Cochrane Central Register of Controlled Trials, trial registries, meeting abstracts, and reference lists from January 1, 1947, to March 2, 2018, were searched. Key search terms included neuroendocrine tumors, gastrointestinal neoplasms, therapy, and randomized controlled trial. STUDY SELECTION: Randomized clinical trials comparing 2 or more therapies in patients with NETs (primarily gastrointestinal and pancreatic) were evaluated. Thirty RCTs met the selection criteria. DATA EXTRACTION AND SYNTHESIS: Pairs of independent reviewers screened studies, extracted data, and assessed the risk of bias. A network meta-analysis with a frequentist approach was used to compare the efficacy of therapies; the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was used. MAIN OUTCOMES AND MEASURES: Disease control, progression-free survival, overall survival, adverse events, and quality of life. RESULTS: The systematic review identified 30 relevant RCTs comprising 3895 patients (48.4% women) assigned to 22 different therapies for NETs. These therapies showed a broad range of risk for serious and nonserious adverse events. The network meta-analyses included 16 RCTs with predominantly a low risk of bias; nevertheless, precision-of-treatment estimates and estimated heterogeneity were limited. The network meta-analysis found 7 therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.35 [95% CI, 0.28-0.45]), everolimus plus somatostatin analogue (HR, 0.35 [95% CI, 0.25-0.51]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.44 [95% CI, 0.26-0.75]), interferon (HR, 0.37 [95% CI, 0.16-0.83]), interferon plus somatostatin analogue (HR, 0.31 [95% CI, 0.13-0.71]), somatostatin analogue (HR, 0.46 [95% CI, 0.33-0.66]), and sunitinib (HR, 0.42 [95% CI, 0.26-0.67]), and 5 therapies for gastrointestinal NETs: bevacizumab plus somatostatin analogue (HR, 0.22 [95% CI, 0.05-0.99]), everolimus plus somatostatin analogue (HR, 0.31 [95% CI, 0.11-0.90]), interferon plus somatostatin analogue (HR, 0.27 [95% CI, 0.07-0.96]), Lu 177-dotatate plus somatostatin analogue (HR, 0.08 [95% CI, 0.03-0.26], and somatostatin analogues (HR, 0.40 [95% CI, 0.21-0.78]) with higher efficacy than placebo and suggests an overall superiority of combination therapies. CONCLUSIONS AND RELEVANCE: The findings from this study suggest that a range of efficient therapies with different safety profiles is available for patients with NETs.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Mentorship has been found as a key factor for a successful and satisfying career in academic medicine and surgery. The present study was conducted to describe the current situation of mentoring in the surgical community in Switzerland and to evaluate sex differences regarding the impact of mentoring on career success and professional satisfaction. METHODS: The study was designed as an anonymous national survey to all members of the Swiss Surgical Society in 2011 (820 ordinary and 49 junior members). It was a 25-item questionnaire addressing mentor-mentee relationships and their impact on the professional front. RESULTS: Of the 869 mailed surveys, 512 responses were received (response rate: 58.9%). Mentor-mentee relationships were reported by 344 respondents (68.1%) and structured mentoring programs were noted in 23 respondents (6.7%). Compared to individuals without mentors, male mentees exhibited significantly higher subjective career advancement (5.4±1.2 vs. 5.0±1.3; p=0.03) and career development (3.3±1.9 vs. 2.5±1.7; p<0.01) scores, but the differences for female mentees were not statistically significant (4.7±1.1 vs. 4.3±1.2, p=0.16; 2.5±1.6 vs. 1.9±1.4, p=0.26; respectively). The pursuit of an academic career was not influenced by the presence of a mentor-mentee relationship for female (p=0.14) or male participants (p=0.22). CONCLUSIONS: Mentor-mentee relationships are important for the career advancement of male surgeons. The reason for the lack of an impact on the careers of female surgeons is difficult to ascertain. However, mentoring also provides lifelong learning and personal development. Thus, specific attention should be paid to the development of more structured mentoring programs for both sexes.
Assuntos
Escolha da Profissão , Docentes de Medicina/estatística & dados numéricos , Mentores/estatística & dados numéricos , Estudantes de Medicina/estatística & dados numéricos , Procedimentos Cirúrgicos Operatórios/educação , Adulto , Idoso , Feminino , Humanos , Aprendizagem , Masculino , Pessoa de Meia-Idade , Satisfação Pessoal , Fatores Sexuais , SuíçaRESUMO
BACKGROUND: Whereas work-hour regulations have been taken for granted since 1940 in other occupational settings, such as commercial aviation, they have been implemented only recently in medical professions, where they lead to a lively debate. The aim of the present study was to evaluate arguments in favour of and against work-hour limitations in medicine given by Swiss surgeons, lawyers, and pilots. METHODS: An electronic questionnaire survey with four free-response items addressing the question of what arguments speak in favour of or against work-hour limitations in general and in medicine was sent to a random sample of board-certified surgeons, lawyers in labour law, and pilots from SWISS International Airlines Ltd. RESULTS: In all, 279/497 (56%) of the respondents answered the survey: 67/117 surgeons, 92/226 lawyers, and 120/154 pilots. Support for work-hour limitations in general and in medicine was present and higher among lawyers and pilots than it was in surgeons (p<0.001). The latter agreed more with work-hour limitations in general than in medicine (p<0.001). The most often cited arguments in favour of work-hour limitations were "quality and patient safety," "health and fitness," and "leisure and work-family balance," whereas the lack of "flexibility" was the most important argument against. Surgeons expected more often that their "education" and the "quality of their work" would be threatened (p<0.001). CONCLUSIONS: Work-hour limitations should be supported in medicine also, but a way must be found to reduce problems resulting from discontinuity in patient care and to minimise the work in medicine, which has no education value.
Assuntos
Aviação , Advogados , Cirurgiões , Inquéritos e Questionários , Trabalho/estatística & dados numéricos , Carga de Trabalho/estatística & dados numéricos , Adulto , Dissidências e Disputas , Humanos , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional/normas , Saúde Ocupacional/estatística & dados numéricos , Fatores de Tempo , Trabalho/normas , Tolerância ao Trabalho Programado , Carga de Trabalho/normasRESUMO
BACKGROUND: The aim of this study was to identify the factors perceived by surgeons that promote surgery as an attractive or unattractive career choice for today's graduates. In addition, it examined whether the perspectives of surgeons in different professional situations converges. The content of work, contextual work conditions, and calling to this job are discussed in the context of choosing surgery as a career. METHODS: Eight hundred sixty-nine surgeons were asked to answer open-ended questions regarding the factors that promote surgery as an attractive or unattractive career choice for today's graduates. Four hundred ninety-two surgeons participated, and 1,525 statements were analyzed using Mayring's content-analyses method. Chi-square tests were used to analyze the differences among hierarchical positions. RESULTS: With respect to the factors that promote surgery as a profession, 40.8% (209/492) of the surgeons stated that surgery is a calling, 29.1% (149/492) of the surgeons provided at least one argument related to the positive task characteristics, and 12.9% (66/492) of the surgeons provided statements related to the positive contextual factors. With respect to the factors that discourage surgery as a profession, 45.7% (234/492) of the surgeons provided at least one argument related to the discouraging work characteristics, and 67.6% (346/492) of the surgeons provided problematic contextual characteristics. CONCLUSION: This study emphasizes the importance of the calling to surgery as an important factor for choosing surgery as a career. However, the extensive workload, training, and poor work-family balance have been identified as factors that discourage graduates from choosing surgery as a career. The identified positive factors could be used to attract and maintain graduates in surgical disciplines.