Well-Differentiated Thyroid Carcinomas: Management of the Central Lymph Node Compartment and Emerging Biochemical Markers

Well-differentiated thyroid cancers (WDTCs) are generally indolent cancers that are associated with a low mortality. Although the incidence of these tumors is increasing, there has not been an associated increase in the mortality rates. As we gain a greater understanding and more experience with these good prognosis cancers, the way in which we treat these tumors is evolving. The definition of persistent or recurrent disease has seen a shift from being a clinical and/or radiological diagnosis to now one based on a biochemical blood marker, thyroglobulin. Central lymph node metastases are a very common problem in WDTC, being present in up to 90% of patients. The optimal surgical management of the central lymph node compartment remains a hotly debated topic. This paper identifies these controversies and presents available data surrounding these issues. Biochemical tumor markers are gaining wider use in practice and in time hopefully provide more specific information with which surgical decision-making can be based. A summary of the clinically available markers is presented

Duodenal gastrinomas, duodenotomy, and duodenal exploration in the surgical management of Zollinger-Ellison syndrome

Studies have shown that the duodenum is a more common site (30–40%) of primary gastrinomas than previously reported. These tumors are often occult to conventional exploration, and their detection requires duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Furthermore, tumors as small as 1 to 2 mm may be associated with lymph node metastases. Seven patients with duodenal gastrinomas treated during a 2-year period are reported. Four had sporadic Zollinger-Ellison syndrome (ZES), and three had multiple endocrine neoplasia type I (MEN-I) syndrome. All seven patients had malignant duodenal gastrinomas as proved by metastatic lymph nodes and in one case a large liver metastasis as well. Local excision of the tumor, lymph node excisions, and in one case liver lobectomy resulted in eugastrinemia in the 4 with sporadic ZES. Two of the three with MEN-I were also eugastrinemic after similar procedures, with the addition of distal pancreatectomy. Duodenotomy is considered an essential procedure in sporadic ZES patients when no pancreatic tumor is found and in all MEN-I/ZES patients, regardless of the pancreatic findings. Regional lymph node excisions are essential when a duodenal tumor has been found . Des études récentes ont démontré que les gastrinomes primitifs étaient localisés au duodénum dans 30 à 40% des cas, beaucoup plus fréquemment que communémment admis. La découverte de ces tumeurs reste souvent difficile par des investigations conventionelles et nécessitent une duodénotomie avec une exploration et une palpation méticuleuses de la muqueuse duodénale éversée. D'aussi petites tumeurs que de 1 ou de 2 mm peuvent être accompagnées de métastases ganglionnaires. Sept cas de gastrinomes duodénaux, traités en deux ans, sont étudiés. Quatre avaient un syndrome de Zollinger-Ellison (SZE) et trois avaient un syndrome MEN-I. Tous ces patients avaient un gastrinome malin car tous avaient des métastases ganglionnaires et dans un cas, des métastases hépatiques. En cas de SZE sporadique, une eugastrinémie a été obtenue par excision de la tumeur, associée à une lymphadénectomie et, dans un cas, à une lobectomie hépatique. Deux des trois patients ayant un syndrome MEN-I sont devenus eugastrinémiques après des interventions similaires associées dans un cas à une pancréatectomie distale. La duodénotomie est un geste essentiel dans le cas d'un SZE sporadique lorsqu'on ne retrouve pas de tumeur, et chez tous les patients ayant un syndrome MEN, quelle que soient les données pancréatiques. La lymphadénectomie régionale est également importante en cas de tumeur duodénale. Estudios recientes han demostrado que el duodeno es un lugar más común (30–40%) de ubicación de gastrinomas primarios de lo que había sido previamente reportado.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41293/1/268_2005_Article_BF01655104.pd

The incidence of bilateral well-differentiated thyroid cancer found at completion thyroidectomy

The purpose of this study was to evaluate the surgical outcome of completion thyroidectomy in patients with presumed unilateral well-differentiated thyroid cancer (WDTC). The medical records of all patients having had unilateral thyroid lobectomy for WDTC, who subsequently underwent completion thyroidectomy, were reviewed. From 1980 to 1991, 60 patients with WDTC underwent completion thyroidectomy. Forty-seven patients had presumed unilateral WDTC, with no evidence of residual disease prior to their completion thyroidectomy. Twenty-five (53%) of these patients were found to have residual neoplastic disease in the neck. In 20 (43%) of 47 patients, a focus of cancer was found in the remaining thyroid lobe and in 5 additional patients no cancer was found in the contralateral lobe, however, unsuspected nodal disease was found. The remaining 13 of the 60 patients presented with either regional recurrence (n=12) or distant metastases (n=1) at the time of their completion thyroidectomy. All (92%) but 1 of these 13 patients had cancer in the remaining thyroid lobe. Multifocal disease in the primary lobe was associated with bilateral thyroid cancer ( p <0.01). Complications were infrequent; transient hypocalcemia occurred in 5 (8%) patients, permanent hypoparathyroidism occurred in 1 (1.7%) patient, and transient recurrent laryngeal nerve palsy occurred in 3 (5%) patients. Residual WDTC was found in 37 (62%) of 60 patients undergoing completion thyroidectomy. Multifocal disease in the primary resected lobe was associated with a high incidence of contralateral thyroid cancer. Completion thyroidectomy is a safe procedure and may prevent the development of regional recurrence by eliminating an unsuspected focus of cancer. Le but de cette étude était d'évaluer l'évolution chirurgicale après thyroïdectomie totale des patients ayant un cancer thyroïdien présumé bien différencié et unilatéral (CTBD). Les données médicales de tous les patients ayant eu une lobectomie unilatérale de la thyroïde pour CTBD et qui ont eu secondairement une totalisation de la thyroïdectomie ont été revues. Entre 1980 et 1991, 60 patients ayant un CTBD ont eu une totalisation de la thyroïdectomie, quarante sept avaient un CTBD présumé unilatéral, sans argument pour une pathologie résiduelle avant la totalisation de la thyroïdectomie (groupe 1). Vingt cinq d'entre eux (53%) se sont avérés avoir un reliquat néoplasique persistant au niveau de la région cervicale. Chez 20/47 (43%) patients, on a retrouvé un foyer de cancer dans le lobe restant de la thyroïde. Chez 5 patients supplémentaires il n'a pas été retrouvé de cancer dans le lobe controlatéral mais une dystrophie nodulaire non suspecte. Les 13/60 patients restants présentaient soit une récidive régionale (12) soit des métastases à distance (1) au moment de la totalisation de la thyroïdectomie (groupe 2). Tous les patients du groupe 2 sauf un (92%) avaient un cancer dans le lobe restant. Une atteinte plurifocale dans le premier lobe était associée avec l'existence d'un cancer bilatéral ( p <0.01). Les complications ont été rares: une hypocalcémie transitoire est survenue chez 5 (8%) patients, une hypoparathyroïdie définitive est apparue chez 1 (1.7%) patient. Une paralysie récurentielle transitoire a été retrouvée chez 3 (5%) patients. Conclusions: Un reliquat de TCBD a été retrouvé chez 37/60 (62%) patients opérés d'une totalisation de thyroïdectomie. L'atteinte multifocale dans le premier lobe réséqué était associée avec une incidence élevée de cancer thyroïdien controlatéral. La totalisation de la thyroïdectomie est une procédure sans risque qui peut prévenir le développement d'une récidive régionale en éliminant un foyer de cancer non suspecté. El propósito del presente estudio fue valorar el resultado quirúrgico de completar a una tiroidectomía total la resección tiroidea realizada en pacientes con cáncer presumiblemente unilateral y bien diferenciado de la glándula tiroides (CTBD). Se revisaron las historias clínicas de todos los pacientes sometidos a lobectomía tiroidea unilateral por CTBD, en quienes subsiguientemente se completó la tiroidectomía, procedimiento que fue realizado en 60 pacientes con CTBD en el período 1980–1991. Cuarenta y siete pacientes tenían CTBD presumiblemente unilateral, sin evidencia de enfermedad residual antes de completarse la tiroidectomía (grupo 1); en veinticinco (53%) de estos pacientes se halló neoplasia residual en el cuello. En 20/47 (43%) pacientes se encontró un foco de cáncer en el lóbulo tiroideo remanente y en 5 casos adicionales aunque no se encontró cáncer en el lóbulo contralateral, se halló extensión ganglionar no sospechada. Los 13/60 pacientes restantes presentaron recurrencia (12) o metástasis distantes (1) en el momento de completarse la tiroidectomía (grupo 2). Todos los pacientes del grupo 2, excepto 1 (92%), presentaban cáncer en el lóbulo remanente. La presencia de enfermedad multifocal en el lóbulo primario apareció asociada con cáncer tiroideo bilateral ( p <0.01). Las complicaciones fueron raras; se presentó hipocalcemia transitoria en 5 (8%) pacientes, hipotiroidismo permanente en 1 (1.7%) y parálisis parcial y transitoria del nervio laríngeo recurrente en 3 (5%). Conclusiones: Se encontró CTBD en 37/60 (62%) pacientes en quienes se completó la tiroidectomía. La presencia de enfermedad multifocal en el lóbulo primario resecado apareció asociada con una alta incidencia de cáncer contralateral. El procedimiento de completar la tiroidectomía aparece como una operación segura que puede prevenir el desarrollo recurrencia regional al eliminar focos insospechados de cáncer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41292/1/268_2005_Article_BF02067365.pd

Differentiated thyroid carcinoma in children and adolescents

From 1936 to 1990, 89 children and adolescents (72 girls and 17 boys) were treated for differentiated thyroid carcinoma at the University of Michigan Medical Center; 58 of these patients were first reported in 1971. Thirty (34%) patients had previously received external irradiation to the head and neck, although only 1 (3%) patient of the last 33 patients seen had this history. Patients first presenting from 1971 to 1990 had less advanced disease than those seen earlier. Also, during this time period, the rate of initial palpable cervical adenopathy fell from 63% to 36%, local infiltration of primary cancer from 31% to 6%, and initial pulmonary metastases from 19% to 6%. The incidence of cervical nodal metastases has remained 88% for 54 years. Papillary or the follicular variant of papillary carcinoma was found in 93% of all patients. Seventy-nine (89%) patients had total or completion total thyroidectomy. Surgical management of lymphatic metastases varied from regional excision of nodes to radical neck dissection. The overall rate of permanent accidental recurrent laryngeal nerve palsy and hypoparathyroidism was 4.5%, although neither has occurred in a child or adolescent undergoing surgery at the center in the past 25 years. The most recent 33 patients had a low rate of local/regional persistence or recurrence. Cervical nodal persistence occurred in 21%; there were no thyroid recurrences. Eighty-two percent of patients received 131 I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative 131 I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma. Entre 1936 et 1990, 89 enfants et adolescents (72 filles et 17 garons) ont été traités pour cancer différencie de la thyroïde au Centre Médical de l'Université de Michigan. Cinquante huit d'entre eux ont fait l'objet d'une publication en 1971. Trente de ces patients (34%) avaient eu une radiothérapie externe au niveau de la tête et/ou du cou, mais ce facteur n'a été retrouvé que chez un des 33 derniers patients (3%). Les patients vus entre 1971 et 1990 avaient une maladie moins avancée. Pendant cette période, le taux d'adénopathies cervicales palpables est passée de 63 à 36%; le pourcentage de patients ayant une infiltration locale, de 31 à 6%, et celui de métastases pulmonaires de 19 à 6%. L'incidence des métastases ganglionnaires cervicales, par contre, est restée de 88% depuis 54 ans. Le cancer était papillaire ou folliculaire dans 93% des cas. Soixante-neuf patients (89%) ont eu une thyroïdectomie totale, soit d'embl%ee soit secondairement. La thérapeutique des métastases ganglionnaires a varié depuis l'exérèse régionale et le curage ganglionnaire cervical. Le taux global de paralysie récurrentielle et de l'hypoparathyroïde était de 4.5%, mais aucune de ces deux complications n'a été observée pour les enfants opérés dans notre centre au cours des 25 dernières années. Parmi les 33 derniers patients, le taux de tissu résiduel ou de récidive était bas. Dans 21% des cas, il persistait du tissu néoplasique après chirurgie, sans récidive. Quatre-vingt pour cent de ces patients ont eu un traitement par l'iode 131. La mortalité à distance était de 2.2%. Nous continuous de recommander une thyroïdectomie totale, une lymphadénectomie cervicale et une iodothérapie post-opératoire par l'iode 131 comme le traitement les plus conservateurs du cancer différencié de la thyroïde chez l'enfant. Ochenta y nueve niños y adolescentes (72 de sexo femenino y 17 de sexo masculino) fuiron tratados por carcinoma tiroideo diferenciado en el Centro Médico de la Universidad de Michigan; 58 de estos pacientes fueron reportados por primera vez en 1971. Treinta pacientes (34%) tenían historia de irradiación a la cabeza y el cuello; sin embargo, solamente uno de los últimos 33 (3%) presentó tal historia. Los pacientes vistos entre 1971 y 1990 exhibían enfermedad menos avanzada que aquellos vistos previamente. Así mismo, la incidencia de adenopatías cervicales palpables descendió de 63% a 36%, la de infiltración local por cáncer primario de 31% a 6% y la de metástasis pulmonares iniciales de 19% a 6%. La incidencia de metástasis ganglionares cervicales se ha mantenido en 88% por 54 años. La variante papilar o folicular del carcinoma papilar se encontró en 93% de los pacientes de la serie. Setenta y nueve pacientes (89%) fueron sometidos a toroidectomía total o a reoperación para completar la tiroidectomía total. El manejo quirúrgico de las metástasis linfáticas varió desde la resección regional de los ganglios hasta la disección radical del cuello. La tasa global de lesión accidental, permanente o temporal, del nervio recurrente laríngeo y de hopoparatiroidismo fue 4.5%, aunque ninguna de estas complicaciones ha ocurrido en un niño o en un adolescente sometido a cirugía en nuestro centro médico en los últimos 25 años. Los últimos 33 pacientes exhibieron una tasa reducida de persistencia o de recurrencia local/regional. La persistencia ganglionar cervical se presentó en 21% de los casos; no hubo recurrencias tiroideas. Ochenta y dos por ciento de los pacientes recibió 131 I. La tassa de mortalidad a largo plazo fui 2.2%. Nuestro grupo continúa preconizando tiroidectomía total, disección ganglionar cervical y terapia postoperatoria con 131 I como la modalidad terapéutica más conservadora en carcinoma diferenciado de la glándula tiroidea en la niñez.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41290/1/268_2005_Article_BF02067317.pd

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Well-Differentiated Thyroid Carcinomas: Management of the Central Lymph Node Compartment and Emerging Biochemical Markers

Well-differentiated thyroid cancers (WDTCs) are generally indolent cancers that are associated with a low mortality. Although the incidence of these tumors is increasing, there has not been an associated increase in the mortality rates. As we gain a greater understanding and more experience with these good prognosis cancers, the way in which we treat these tumors is evolving. The definition of persistent or recurrent disease has seen a shift from being a clinical and/or radiological diagnosis to now one based on a biochemical blood marker, thyroglobulin. Central lymph node metastases are a very common problem in WDTC, being present in up to 90% of patients. The optimal surgical management of the central lymph node compartment remains a hotly debated topic. This paper identifies these controversies and presents available data surrounding these issues. Biochemical tumor markers are gaining wider use in practice and in time hopefully provide more specific information with which surgical decision-making can be based. A summary of the clinically available markers is presented.Peer Reviewe

Staging for Papillary Thyroid Cancer

Staging is an essential component of cancer care. It is necessary to estimate prognosis, develop treatment plans, facilitate communication, and establish a bases for research efforts. Various clinicopathologic features of papillary thyroid cancer have been used to create a large number of staging systems. These systems incorporate preoperative risk factors, intraoperative findings, and postoperative results to estimate mortality and to a lesser degree recurrence. Preoperatively environmental exposures, age, gender, and genetics contribute to risk assessment in addition to physical exam and ultrasonographic findings. Intraoperative thyroid gland and lymph node assessment is important for guiding management both intraoperatively and postoperatively. Finally, postoperative response to therapy is becoming a guiding principle in the dynamic staging of patients with papillary thyroid cancer. This chapter discusses the evolution of staging systems for papillary thyroid cancer as well as patient and tumor characteristics that are evaluated at different time intervals as part of the staging process

Duodenal Hematoma – A Case Report of Duodenal Atresia following Conservative Management of a Duodenal Hematoma

In children, duodenal hematomas following blunt abdominal trauma are routinely treated conservatively. A case of a two-and-a-half-year-old female in whom conservative management was unsuccessful is presented. At surgery she was found to have an atretic duodenum secondary to the duodenal hematoma. Although uncommon, fibrotic stenosis must be considered in a patient who fails to show resolution of duodenal obstruction following conservative treatment for a duodenal hematoma