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BACKGROUND: The aim of this study is to describe the management and associated follow-up strategies adopted by thyroid surgeons with different surgical volumes when loss of signal (LOS) occurred on the first side of planned bilateral thyroid surgery, and to further define the consensus on intraoperative neuromonitoring (IONM) applications. METHODS: The International Neural Monitoring Study Group (INMSG) web-based survey was sent to 950 thyroid surgeons worldwide. The survey included information on the participants, IONM team/equipment/procedure, intraoperative/postoperative management of LOS, and management of LOS on the first side of thyroidectomy for benign and malignant disease. RESULTS: Out of 950, 318 (33.5%) respondents completed the survey. Subgroup analyses were performed based on thyroid surgery volume: <50 cases/year (n = 108, 34%); 50 to 100 cases/year (n = 69, 22%); and >100 cases/year (n = 141, 44.3%). High-volume surgeons were significantly (P < .05) more likely to perform the standard procedures (L1-V1-R1-S1-S2-R2-V2-L2), to differentiate true/false LOS, and to verify the LOS lesion/injury type. When LOS occurs, most surgeons arrange otolaryngologists or speech consultation. When first-side LOS occurs, not all respondents decided to perform stage contralateral surgery, especially for malignant patients with severe disease (eg, extrathyroid invasion and poorly differentiated thyroid cancer). CONCLUSIONS: Respondents felt that IONM was optimized when conducted under a collaborative team-based approach, and completed IONM standard procedures and management algorithm for LOS, especially those with high volume. In cases of first-site LOS, surgeons can determine the optimal management of disease-related, patient-related, and surgical factors. Surgeons need additional education on LOS management standards and guidelines to master their decision-making process involving the application of IONM.
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Tiroidectomía , Humanos , Tiroidectomía/métodos , Encuestas y Cuestionarios , Monitorización Neurofisiológica Intraoperatoria , Enfermedades de la Tiroides/cirugía , Pautas de la Práctica en Medicina/estadística & datos numéricos , Traumatismos del Nervio Laríngeo Recurrente/prevención & control , Traumatismos del Nervio Laríngeo Recurrente/etiología , Parálisis de los Pliegues Vocales/etiología , Femenino , MasculinoRESUMEN
PURPOSE: No genomic data have been put forth that prove beyond a shadow of doubt that sporadic medullary thyroid cancer (MTC) occurs in infancy, childhood, and/or adolescence. METHODS: This was a retrospective comparative study of consecutive patients with MTC who had neck surgery at a tertiary center over a 30-year period. RESULTS: Included were 1252 patients with MTC (337 hereditary and 915 sporadic), of whom 107 (8.5%) were operated before the age of 18 yrs. Only 4 (3.7%) of the 107 pediatric patients, aged 14, 16, 17 and 17 years, had sporadic MTC. These 4 patients, 3 of whom had been referred for completion surgery, revealed much larger thyroid tumors (medians of 20 mm vs. 1.5-5 mm) than the 103 pediatric patients with hereditary MTC. As for extrathyroid extension and nodal metastases, the 4 patients with sporadic MTC were more comparable to the 37 carriers of highest-risk mutations, 31 (84%) of whom were index patients with de novo disease, than to the 66 carriers of high-risk, intermediate-risk, or low-risk RET mutations (25-38% vs. 0-8%, and medians of 9-9.5 vs. 0 node metastases after dissection of more (medians of 72-91.5 vs. 4.5-9) nodes). CONCLUSION: Sporadic MTC, arising rarely, if ever, below the age of 14 years, is exceptional in infancy and childhood, and infrequent in adolescence. At diagnosis, it is almost as widely metastatic as hereditary MTC of the highest-risk category which almost always, like sporadic MTC, presents as de novo disease.
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Carcinoma Medular , Carcinoma Neuroendocrino , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Adolescente , Estudios Retrospectivos , Masculino , Femenino , Niño , Carcinoma Neuroendocrino/genética , Carcinoma Neuroendocrino/patología , Carcinoma Medular/genética , Carcinoma Medular/congénito , Carcinoma Medular/patología , Preescolar , Proteínas Proto-Oncogénicas c-ret/genética , Tiroidectomía , Lactante , Neoplasia Endocrina Múltiple Tipo 2a/genética , Adulto Joven , MutaciónRESUMEN
Medullary thyroid cancer (MTC) is the most frequent manifestation of multiple endocrine neoplasia type 2 (MEN2) that determines the oncological outcome. Germline mutations in the rearranged during transfection (RET) protooncogene, a tumor suppressor gene on chromosome 10q11.2, were identified 30 years ago as the genetic basis of MEN2 and published in 1993 and 1994. These seminal findings gave rise to the concept of prophylactic thyroidectomy for asymptomatic gene mutation carriers based on a positive RET gene test, which has become the standard of care ever since. Clinical genetic investigations showed genotype-phenotype correlations with respect to the individual gene mutation regarding the penetrance and onset of MTC and to a lesser extent also with respect to the other components of MEN2, pheochromocytoma and primary hyperparathyroidism. From this a clinically relevant risk stratification could be derived. Initially, the optimal timing of prophylactic thyroidectomy was primarily based on the RET genotype alone, which was not sufficient for a precise age recommendation and subsequently required additional consideration of calcitonin serum levels for fine tuning. Calcitonin levels first show the risk of lymph node metastasis when they exceed the upper normal limit of the assay independent of carrier age and RET mutation. Routine calcitonin screening of patients with nodular thyroid disease, screening of families on identification of MEN2 index patients, and pre-emptive thyroidectomy in carriers of gene mutations with normal calcitonin levels have led to the fact that nowadays, 30 years after the first description of the gene mutations causing the disease, the life-threatening hereditary MTC has become curable: a shining example for the success of translational transnational medical research for the benefit of patients.
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Neoplasia Endocrina Múltiple Tipo 2a , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides , Tiroidectomía , Investigación Biomédica Traslacional , Humanos , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/prevención & control , Proteínas Proto-Oncogénicas c-ret/genética , Neoplasia Endocrina Múltiple Tipo 2a/genética , Neoplasia Endocrina Múltiple Tipo 2a/cirugía , Neoplasia Endocrina Múltiple Tipo 2a/patología , Carcinoma Medular/genética , Carcinoma Medular/cirugía , Carcinoma Medular/congénito , Carcinoma Medular/patología , Procedimientos Quirúrgicos Profilácticos , Carcinoma Neuroendocrino/genéticaRESUMEN
Background: Skip metastases, node metastases in the lateral neck sparing the ipsilateral central neck, challenge the current concept of central-to-lateral lymphatic spread. This study sought to delineate patterns of central and lateral neck involvement in unilateral papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC). Methods: This was a retrospective correlative analysis of nodal patterns in surgical specimens from patients with unilateral PTC or MTC who had undergone thyroidectomy with at least ipsilateral central neck dissection between November 1994 and January 2024 at a tertiary referral center. Results: Included were 833 patients with unilateral PTC and 640 patients with unilateral MTC. Simultaneous presence or absence of node metastases was noted in ipsilateral central and lateral neck compartments in 76.6-78.1% of patients with PTC (both node positive in 27.0-54.7% and both node negative in 23.4-49.6%) and 77.3-80.0% of patients with MTC (both node positive in 26.6-33.2% and both node negative in 44.1-53.4%). Only one ipsilateral neck compartment was node positive in 21.9-23.4% of patients with PTC and 20.0-22.7% of patients with MTC. The ipsilateral central, but not the ipsilateral lateral compartment, was node positive in 8.8-16.9% with PTC and 8.6-8.8% of patients with MTC, whereas the ipsilateral lateral, but not the ipsilateral central compartment, was node positive in 6.5-13.1% with PTC and 11.3-14.1% with MTC. Ipsilateral lateral neck involvement sparing the ipsilateral central neck was 1.5-2 times more frequent in patients with node positive MTC than patients with node positive PTC (24.2-25.2% vs. 12.9-17.1%). Greater numbers of node metastases in the ipsilateral central neck compartment were associated with more frequent involvement of the ipsilateral lateral, contralateral central, and contralateral lateral neck compartments. Thyroid tumor diameter intensified nodal spread without changing nodal spread patterns. Conclusions: These histopathological findings, which need to be interpreted in light of the respective tumor biology, offer an unprecedented glimpse at the metastatic patterns of unilateral PTC and MTC. Customizing neck dissection to the patterns of nodal spread, considering operative status (initial vs. reoperative surgery) and experience with neck dissection, may require more frequent concomitant dissections of ipsilateral central and ipsilateral lateral neck compartments.
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Carcinoma Neuroendocrino , Metástasis Linfática , Disección del Cuello , Cáncer Papilar Tiroideo , Neoplasias de la Tiroides , Tiroidectomía , Humanos , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Carcinoma Neuroendocrino/patología , Carcinoma Neuroendocrino/cirugía , Cáncer Papilar Tiroideo/patología , Cáncer Papilar Tiroideo/cirugía , Anciano , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Cuello/patología , Adulto JovenRESUMEN
The age-specific development of the three constituent components of multiple endocrine neoplasia type 2 (MEN 2) is incompletely characterized for many of the >30 causative rearranged during transfection (RET) mutations, which this genetic association study aimed to specify. Included in the study were 683 carriers of heterogeneous RET germline mutations: 53 carriers with 1 highest-risk mutation (codon 918); 240 carriers with 8 different high-risk mutations (codon 634); 176 carriers with 16 different intermediate-risk mutations (codon 609, 611, 618, 620, or 630); and 214 carriers with 6 different low-risk mutations (codon 768, 790, 804, or 891).There was a strong genotype-specific development of MEN 2 constituent components, with distinct age gradients from C cell disease to node negative medullary thyroid cancer (MTC), from node negative to node positive MTC, from node positive MTC to pheochromocytoma, and from pheochromocytoma to primary hyperparathyroidism. Primary hyperparathyroidism was not observed among the 53 MEN 2B patients who carried highest-risk mutations (age range: 0.5-50 years), of whom no more than 12 (23%) and 3 (6%) carriers were older than age 30 years and 35 years, respectively. The age-specific development of MTC differed significantly between the four RET risk categories, whereas the age-specific development of pheochromocytoma differed significantly only between the two strongest RET risk categories. No significant differences were noted in the development of primary hyperparathyroidism. These findings delineate age-specific disease manifestation corridors for the three constituent components of MEN 2 by RET genotype. These corridors are useful for initial risk assessment and organ-specific surveillance of newly identified RET carriers going forward.
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Neoplasias de las Glándulas Suprarrenales , Genotipo , Neoplasia Endocrina Múltiple Tipo 2a , Feocromocitoma , Proteínas Proto-Oncogénicas c-ret , Neoplasias de la Tiroides , Humanos , Proteínas Proto-Oncogénicas c-ret/genética , Persona de Mediana Edad , Adulto , Neoplasia Endocrina Múltiple Tipo 2a/genética , Adolescente , Masculino , Femenino , Neoplasias de la Tiroides/genética , Adulto Joven , Feocromocitoma/genética , Niño , Anciano , Preescolar , Neoplasias de las Glándulas Suprarrenales/genética , Lactante , Mutación de Línea Germinal , Carcinoma Neuroendocrino/genética , Heterocigoto , Hiperparatiroidismo Primario/genética , Neoplasia Endocrina Múltiple Tipo 2b/genética , Anciano de 80 o más AñosRESUMEN
[This corrects the article DOI: 10.3389/fped.2023.1170563.].
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BACKGROUND: Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)). METHODS: We recruited 77 patients with relapsing-remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse. RESULTS: After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029). CONCLUSIONS: Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.
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Biomarcadores , Proteína Ácida Fibrilar de la Glía , Imagen por Resonancia Magnética , Proteínas de Neurofilamentos , Humanos , Masculino , Femenino , Adulto , Proteína Ácida Fibrilar de la Glía/líquido cefalorraquídeo , Proteína Ácida Fibrilar de la Glía/sangre , Proteínas de Neurofilamentos/sangre , Proteínas de Neurofilamentos/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Biomarcadores/sangre , Estudios Transversales , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/sangre , Esclerosis Múltiple Recurrente-Remitente/patología , Persona de Mediana Edad , Adulto Joven , Axones/patología , Neuroglía/patología , Enfermedades Desmielinizantes/líquido cefalorraquídeo , Enfermedades Desmielinizantes/diagnóstico por imagen , Enfermedades Desmielinizantes/sangreRESUMEN
(1) Background: The wider adoption of a preoperative ultrasound and calcitonin screening complemented by an intraoperative frozen section has increased the number of patients with occult sporadic medullary thyroid cancer (MTC). These advances offer new opportunities to reduce the extent of the initial operations, minimizing operative morbidity and the risk of postoperative thyroxin supplementation without compromising the cure. (2) Methods: This systematic review of the international literature published in the English language provides a comprehensive update on the latest progress made in the risk-adapted surgery for sporadic and hereditary MTC guided by an intraoperative frozen section. (3) Results: The current evidence confirms the viability of a hemithyroidectomy for desmoplasia-negative sporadic MTC. To add an extra safety margin, the hemithyroidectomy may be complemented by a diagnostic ipsilateral central node dissection. Despite the limited extent of the surgery, all the patients with desmoplasia-negative sporadic tumors achieved a biochemical cure with excellent clinical outcomes. A hemithyroidectomy decreases the need for postoperative thyroxine substitution, but a total thyroidectomy may be required for bilateral nodular thyroid disease. Hereditary MTC is a different issue. Because each residual thyroid C cell carries its own risk of malignant progression, a total thyroidectomy remains mandatory for hereditary MTC. (4) Conclusion: In experienced hands, a hemithyroidectomy, which minimizes morbidity without compromising the cure, is an adequate therapy for desmoplasia-negative sporadic MTC.
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Post-surgical reproductive performance following ovine caesarean section has not been well studied. To assess any direct effects of surgical delivery in the absence of confounders such as dystocia or underlying diseases, we studied elective surgery performed in healthy animals for teaching purposes. Four hundred and eleven paired breeding records following vaginal delivery (n = 233), elective caesarean section (n = 122), and subsequent further vaginal deliveries in animals with a history of one prior elective caesarean operation (n = 56) were evaluated retrospectively. The overall subsequent pregnancy rate was 95%. Multivariable statistical analyses did not reveal any significant influence of planned caesarean surgery on subsequent conception, stillbirth, perinatal lamb mortality, lamb birth weights, or the incidence of premature foetal death (mummification and abortion). A significantly higher number of mating attempts was, however, necessary. Also, a significant reduction in litter size was seen in the first pregnancy immediately following a surgical delivery in comparison to animals which had previously only delivered vaginally (p = 0.001), but litter size returned to pre-caesarean levels in further follow-up pregnancies in animals with a history of one elective caesarean section (p = 0.436). Subsequent long-term reproductive performance of sheep following elective caesarean section is thus excellent, and the results encourage retention for breeding.
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Objective: Approximately 50% of adolescents who have undergone scoliosis surgery still experience severe pain one year postoperatively. We explored the postoperative pain trajectory and the potential value of preoperative Thermal Quantitative Sensory Testing (T-QST) as predictor of chronic postsurgical pain after scoliosis surgery. Design: Single-center prospective cohort study in adolescents undergoing scoliosis surgery. Outcomes: Prevalence of chronic postsurgical pain (CPSP) one year after scoliosis surgery and postsurgical pain course during this year. The need for rescue medication and the relationship between pre-operative T-QST, acute pain and CPSP. Results: Thirty-nine patients (mean age 13.9 years; SD 1.9 years) completed the study. One year postoperatively, ten patients (26%) self-reported pain [numeric rating scale (NRS) score ≥ 4]) when moving and two (5%) when in rest. Four of these patients (10.3%) experienced neuropathic pain. The pre-operative cold pain threshold was lower (p = 0.002) in patients with CPSP at 12 months. Preoperative cold and heat pain thresholds were correlated with the number of moderate or severe pain reports (NRS ≥ 4) in the first week postoperatively (r -.426; p = 0.009 and r.392; p = 0.016, respectively). Conclusions: One year after scoliosis surgery, a significant part of patients (26%) still reported pain, some with neuropathic characteristics. Better diagnosis and treatment is needed; our study suggests that T-QST could be further explored to better understand and treat children with this negative outcome.
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BACKGROUND: Fighter aircraft pilots are regularly exposed to physiological challenges from high acceleration (Gz) forces, as well as increased breathing pressure and oxygen supply in the support systems. We studied whether effects on the lung and systemic oxidative stress were detectable after real training flights comprising of a wide variety of exposure conditions, and their combinations. METHODS: Thirty-five pilots of the German Air Force performed 145 flights with the Eurofighter Typhoon. Prior to and after flight lung diffusing capacity for carbon monoxide (DLCO) and nitric oxide (DLNO), alveolar volume (VA), and diffusing capacities per volume (KCO, KNO) were assessed. In addition, the fractional concentration of exhaled nitric oxide (FeNO) was determined, and urine samples for the analysis of molecular species related to 8-hydroxy-2'-deoxyguanosine (8-OHdG) were taken. For statistical analysis, mixed ANOVA models were used. RESULTS: DLNO, DLCO, KNO, KCO and VA were reduced (p < 0.001) after flights, mean ± SD changes being 2.9 ± 5.0, 3.2 ± 5.2, 1.5 ± 3.7, 1.9 ± 3.7 and 1.4 ± 3.1%, respectively, while FeNO decreased by 11.1% and the ratio of 8-OHdG to creatinine increased by 15.7 ± 37.8%. The reductions of DLNO (DLCO) were smaller (p < 0.001) than those of KNO (KCO). In repeated flights on different days, baseline values were restored. Amongst various flight parameters comprising Gz-forces and/or being indicative of positive pressure breathing and oxygenation support, the combination of long flight duration and high altitude appeared to be linked to greater changes in DLNO and DLCO. CONCLUSIONS: The pattern of reductions in diffusing capacities suggests effects arising from atelectasis and increased diffusion barrier, without changes in capillary blood volume. The decrease in exhaled endogenous NO suggests bronchial mucosal irritation and/or local oxidative stress, and the increase in urinary oxidized guanosine species suggests systemic oxidative stress. Although changes were small and not clinically relevant, their presence demonstrated physiological effects of real training flights in a modern 4th generation fighter jet.
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Pulmón , Óxido Nítrico , Humanos , Capacidad de Difusión Pulmonar/fisiologíaRESUMEN
Thyroid cancer is the only nonreproductive cancer with striking female predominance, although men with thyroid cancer develop more aggressive disease. This study aimed to quantify sex-specific differences in medullary thyroid cancer (MTC) spread after controlling for primary thyroid tumor size. Included in this retrospective analysis were all patients with unilateral solitary MTC who underwent initial neck surgery at a tertiary referral center. A total of 565 patients, 255 men and 310 women, were identified, of whom 467 had sporadic and 98 hereditary MTC. When stratified by sex, and after correction for multiple testing, men had higher preoperative basal calcitonin levels (medians of 655 vs 181 pg/mL; P < 0.001), more frequent extrathyroid extension (25 vs 9%; P < 0.001) and node metastasis (53 vs 27%; P < 0.001) with more involved nodes (medians of 2 vs 0 nodes; P < 0.001) than women but achieved less often biochemical cure (53 vs 74%; P < 0.001). Although absent in patients with very small (≤5 mm) thyroid tumors, sex disparities were immediately apparent in patients with 5.1-40 mm (node metastasis and biochemical cure) and 10.1-40 mm (extrathyroid extension) large thyroid tumors but were lost in patients with thyroid tumors >40 mm as women caught up. Sex disparities were strongest for node metastasis with a 27-41% (overall 24.0%) point difference, followed by biochemical cure with a -15-35% (overall -20.3%) point difference and extrathyroid extension with a 17-24% (14.2% overall) point difference. These findings indicate that the male predominance in MTC aggressiveness is largely biologically driven, warranting further research.
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Carcinoma Neuroendocrino , Escisión del Ganglio Linfático , Neoplasias de la Tiroides , Humanos , Masculino , Femenino , Estudios Retrospectivos , Caracteres Sexuales , Tiroidectomía , Neoplasias de la Tiroides/patologíaRESUMEN
INTRODUCTION: Propofol and sevoflurane have a long history in pediatric anesthesia. Combining both drugs at low dose levels offers new opportunities. However, monitoring the hypnotic effects of this drug combination in children is challenging, because the currently available processed EEG-based systems are insufficiently validated in young children and the co-administration of anesthetics. This study investigated electroencephalographic density spectral array monitoring during propofol/sevoflurane coadministration with fixed sevoflurane- and variable propofol dosages. PATIENTS AND METHODS: We analyzed the density spectral array pattern recorded during propofol/sevoflurane anesthesia in pediatric patients from birth to 11 years of age. Data from 78 patients were suitable for analysis. The primary outcome parameter of this study was the correlation between variable propofol dosages and the expression of the four electroencephalogram frequency bands ß, α, θ, and δ. The main secondary outcome parameters were the intra-operative total EEG power and the prevalence of burst suppression. RESULTS: In patients above the age of 1 year, a dose-dependent correlation between the propofol dosage and the relative percentage of ß (-12.2%, p < 0.001) and δ (5.1%, p < 0.001) was found. There was an age-dependent trend toward increasing mean EEG power, with the most significant increase in the first year of life. In 14.1% of our patients, at least one episode of burst suppression occurred. CONCLUSION: DSA-guided augmentation of propofol anesthesia with sevoflurane provides sufficient depth of anesthesia at doses usually considered sub-anesthetic in children, leading to less anesthetic drug exposure for the individual child.
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Anestesia , Anestésicos por Inhalación , Anestésicos , Éteres Metílicos , Propofol , Niño , Preescolar , Humanos , Anestésicos Intravenosos/farmacología , Electroencefalografía , Éteres Metílicos/farmacología , Sevoflurano , Recién Nacido , LactanteRESUMEN
BACKGROUND: Approximately 21 900 women and 35 300 men developed lung cancer in Germany in 2018, and 16 999 women and 27 882 men died of it. The outcome mainly depends on the tumor stage. In early stages (stage I or II), treatment can be curative; unfortunately, because early-stage lung cancers are generally asymptom - atic, 74% of women and 77% of men already have advanced-stage disease (stage III or IV) at the time of diagnosis. Screening with low-dose computed tomography is an option enabling early diagnosis and curative treatment. METHODS: This review is based on pertinent articles retrieved by a selective search of the literature on screening for lung cancer. RESULTS: In the studies of lung cancer screening that have been published to date, sensitivity ranged from 68.5% to 93.8%, and specificity from 73.4% to 99.2%. A meta-analysis by the German Federal Office for Radiation Protection revealed a 15% reduction in lung cancer mortality when low-dose computed tomography was used in persons who were judged to be at high risk for lung cancer (risk ratio [RR] 0.85, 95% confidence interval [0.77; 0.95]). 1.9% of subjects died in the screening arm of the meta-analysis, and 2.2% in the control group. The observation periods ranged from 6.6 to 10 years; false-positive rates ranged from 84.9% to 96.4%. Malignant findings were confirmed in 45% to 70% of the biopsies or resective procedures that were performed. CONCLUSION: Systematic lung cancer screening with low-dose CT lowers mortality from lung cancer in (current or former) heavy smokers. This benefit must be weighed against the high rate of false-positive findings and overdiagnoses.
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Neoplasias Pulmonares , Trastornos del Inicio y del Mantenimiento del Sueño , Masculino , Humanos , Femenino , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Detección Precoz del Cáncer , Tamizaje Masivo/métodos , SueñoRESUMEN
Research on charge-density-wave (CDW) ordered transition-metal dichalcogenides continues to unravel new states of quantum matter correlated to the intertwined lattice and electronic degrees of freedom. Here, we report an inelastic x-ray scattering investigation of the lattice dynamics of the canonical CDW compound 2H-TaSe2 complemented by angle-resolved photoemission spectroscopy and density functional perturbation theory. Our results rule out the formation of a central-peak without full phonon softening for the CDW transition in 2H-TaSe2 and provide evidence for a novel precursor region above the CDW transition temperature TCDW, which is characterized by an overdamped phonon mode and not detectable in our photoemission experiments. Thus, 2H-TaSe2 exhibits structural before electronic static order and emphasizes the important lattice contribution to CDW transitions. Our ab-initio calculations explain the interplay of electron-phonon coupling and Fermi surface topology triggering the CDW phase transition and predict that the CDW soft phonon mode promotes emergent superconductivity near the pressure-driven CDW quantum critical point.
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The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAFV600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations (P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation (P < 0.01). This association was not observed for BRAFV600E mutations (P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy.
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Carcinoma Papilar , Telomerasa , Neoplasias de la Tiroides , Humanos , Cáncer Papilar Tiroideo/genética , Cáncer Papilar Tiroideo/radioterapia , Radioisótopos de Yodo/uso terapéutico , Telomerasa/genética , Proteínas Proto-Oncogénicas B-raf/genética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/patología , Biomarcadores , MutaciónRESUMEN
BACKGROUND: The absence of primary tumor desmoplasia, a marker of node metastases, on frozen section may help reduce the extent of surgery without compromising the biochemical cure. We aimed to clarify whether hemithyroidectomy with diagnostic ipsilateral central neck dissection can replace total thyroidectomy with routine central neck dissection in patients with sporadic medullary thyroid cancer. METHODS: We retrospectively evaluated data collected from patients who had undergone primary neck surgery for hypercalcitoninemic sporadic medullary thyroid cancer between January 2017 and December 2022 at one institution. RESULTS: Of the 25 patients we examined, 19 had desmoplasia-negative and 6 desmoplasia-positive primary thyroid tumors on frozen section. The desmoplasia-negative patients had undergone less surgery with fewer nodes removed than the desmoplasia-positive patients (medians of 6 vs 31 nodes, P < .001). The desmoplasia-negative patients had predominantly undergone hemithyroidectomy with ipsilateral central neck dissection. None of the desmoplasia-negative tumors was multifocal (0 of 19 desmoplasia-negative vs 2 of 6 desmoplasia-positive or 0% vs 33%, P = .050) or node-positive (0 of 19 vs 6 of 6 patients or 0% vs 100%; medians of 0 vs 3.5 node metastases; both P < .001). Despite limited surgery, all desmoplasia-negative patients attained and maintained biochemical cure. CONCLUSION: Hemithyroidectomy combined with diagnostic ipsilateral central neck dissection is a viable risk-reducing and curative strategy for desmoplasia-negative and node-negative, nonmetastatic unifocal tumors, for which we propose the term sporadic noninvasive medullary thyroid neoplasm (SNMTP).
Asunto(s)
Neoplasias de la Tiroides , Tiroidectomía , Humanos , Estudios Retrospectivos , Neoplasias de la Tiroides/cirugía , Neoplasias de la Tiroides/patología , Disección del CuelloRESUMEN
Abnormalities are indispensable for studying normal biological processes and mechanisms. In the present work, we draw attention to the remarkable phenomenon of a perpetually and robustly upregulated gene, the thyroglobulin gene (Tg). The gene is expressed in the thyroid gland and, as it has been recently demonstrated, forms so-called transcription loops, easily observable by light microscopy. Using this feature, we show that Tg is expressed at a high level from the moment a thyroid cell acquires its identity and both alleles remain highly active over the entire life of the cell, i.e., for months or years depending on the species. We demonstrate that this high upregulation is characteristic of thyroglobulin genes in all major vertebrate groups. We provide evidence that Tg is not influenced by the thyroid hormone status, does not oscillate round the clock and is expressed during both the exocrine and endocrine phases of thyrocyte activity. We conclude that the thyroglobulin gene represents a unique and valuable model to study the maintenance of a high transcriptional upregulation.