Janice L. Pasieka

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 received131I. The long-term mortality rate was 2.2%. We continue to advocate total thyroidectomy, cervical lymph node dissection, and postoperative131I therapy as the most conservative treatment regimen for children with differentiated thyroid carcinoma.RésuméEntre 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 lUniversité de Michigan. Cinquante huit dentre eux ont fait lobjet dune 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 na 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 dadénopathies 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%. Lincidence 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 dembl%ee soit secondairement. La thérapeutique des métastases ganglionnaires a varié depuis lexérèse régionale et le curage ganglionnaire cervical. Le taux global de paralysie récurrentielle et de lhypoparathyroïde était de 4.5%, mais aucune de ces deux complications na 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 liode 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 liode 131 comme le traitement les plus conservateurs du cancer différencié de la thyroïde chez lenfant.ResumenOchenta 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 recibió131I. La tassa de mortalidad a largo plazo fui 2.2%. Nuestro grupo continúa preconizando tiroidectomía total, disección ganglionar cervical y terapia postoperatoria con131I como la modalidad terapéutica más conservadora en carcinoma diferenciado de la glándula tiroidea en la niñez.

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.RésuméLe but de cette étude était dévaluer lévolution 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 dentre 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 na 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 lexistence dun 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 dune totalisation de thyroïdectomie. Latteinte 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 dune récidive régionale en éliminant un foyer de cancer non suspecté.ResumenEl 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.

Feasibility of sentinel lymph node biopsy and lymphatic mapping in nodular thyroid neoplasms

Although the prognostic significance of occult lymph node metastases in thyroid cancer remains controversial, identifying these patients may help direct therapy. The purpose of this study was to determine the feasibility and safety of sentinel lymph node biopsy (SLNBx) in thyroid nodular disease. Patients undergoing thyroid resection, with no evidence of clinical lymphadenopathy, were enrolled. The nodule was injected with isosulfan blue vital dye. Blue-stained lymphatic channels were traced within the central compartment to the SLN, which was excised. A total of 40 patients underwent SLNBx; lymphatics were seen in 31 patients, and SLNs were found in 26. In 11 patients the lymphatic vessels were traced through the central compartment into the lateral or mediastinal compartments, although a central SLN was retrieved in only 6. Of the 18 patients with benign neoplasms, 14 had benign SLNs, and no SLN was found in 4. A thyroid lymphoma patient had a true positive SLN. In the 12 patients with papillary thyroid cancer (PTC), 6 had true positive SLNs, and 2 had a true negative SLN. In one patient with metastatic PTC, the parathyroid stained blue. Another patient with PTC had lateral lymphatic channels, but no SLN was found. There were two false negatives, proven by a node dissection in one and lateral uptake on 131I scanning in the other. There were no postoperative complications. SLNBx for thyroid disease is feasible and safe. Potential staining of the parathyroids makes their identification before injection mandatory. The variable lymphatic drainage patterns and the two false-negative nodes indicate that further investigation is required before the procedure can be recommended for patients with thyroid disease.

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.RésuméDes 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. Daussi 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 dun SZE sporadique lorsquon 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.ResumenEstudios 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.Estos tumores frecuentemente están ocultos en la exploración convencional y requieren duodenotomía y meticulosa evaluación de la mucosa por eversión y palpación directa para su detección. Además, tumores pequeños, de 1 y 2 mm, pueden estar asociados con metástasis ganglionares. Se informan 7 casos adicionales de gastrinomas duodenales tratados en un periodo de dos años. Cuatro tenían síndrome de Zollinger-Ellison esporádico (SZE) y tres síndrome de NEM-1. Todos los 7 pacientes tenían gastrinomas duodenales malignos comprobado por la presencia de ganglios linfáticos metastásicos y, en un caso, también una metástasis hepática grande. La resección local del tumor, la disección de los ganglios y, en un caso, la lobectomía hepática, resultaron en eugastrinemia en los cuatro pacientes con SZE. Dos de los tres con SNEM-1 también aparecieron eugastrinémicos luego de procedimientos similares y la adición de pancreatectomía distal.La duodenotomía es considerada un procedimiento esencial en pacientes con SZE esporádico cuando no se encuentra tumor pancreático, en todos los pacientes con SNEM-1 SZE, no importa cuales sean los hallazgos en el páncreas. La resección de los ganglios regionales también es esencial en presencia de tumor duodenal.

What Should We Tell Our Patients? Lifetime Guarantee or is it 5- to 10-year Warranty on a Parathyroidectomy for Primary Hyperparathyroidism?

In the endocrine surgical world, a new debate has emerged—that being which operation is the best for sporadic primary hyperparathyroidism (HPT). Advances in technology, preoperative imaging, and intra-operative adjuncts have expanded the operative choices for our patients [1, 2]. No longer is it a mandatory 4-gland bilateral parathyroid exploration as it was in the days of Oliver Cope [3]. Today, with appropriate patient selection, surgeons are successfully utilizing a more focused approach such as imaged-directed or unilateral explorations in order to avoid a bilateral exploration and the additional risks [4–6]. However, recent data have emerged that 10-year cure rates following a focused approach may be lower than bilateral exploration [7, 8]. It has been long recognized that if one looks at all the glands at the initial operation, more histological abnormal glands are found [9]. Siperstein et al. found unrecognized multi-gland disease 16 % of the time when they proceeded to a 4-gland exploration following a ‘successful’ focused parathyroidectomy [10]. That, along with the fact that the now-recognized incidence of elevated PTH with normal calcium levels following parathyroid surgery (a potential harbinger for recurrence) appears to be higher following a focused approach compared to a bilateral exploration [11–13], has at least caused me to pause and reflect on which operation for sporadic HPT is the best. I attempted to bring about some reflection among the audience on this very topic at the 2014 Asian Association of Endocrine Surgeons meeting in Sri Lanka. I presented data demonstrating a long-term recurrence rate of 4–6 % with a focused approach compared to 1–2 % with a bilateral operation [7, 8]. Yet given over 80 % of patients with sporadic HPT have solitary adenomas, clearly the majority do achieve a life-long cure from a focused approach. I concluded my talk by stating that parathyroid surgeons need to reflect on the how far the pendulum has swung away from the gold-standard operation. A focused approach may not provide as robust long-term cure as the bilateral operation does, but it clearly has many advantages and should not be totally abandoned as some have advocated [8]. Since access to advanced preoperative imaging and adjuncts like intra-operative PTH (iPTH) are not always possible or have proven not to be cost-effective in some surgical units, many surgeons are providing an operative strategy that best suits their patients within their local healthcare environment and this is not wrong. We have to recognize that what works for one unit may not be the best strategy for another. Surgeons need to define their ‘go to operation’ and how successful it has been both in shortand long-term followup. When I sat down, the senior author of the Norlen paper (LD) leaned over and asked me ‘why do we endocrine surgeons feel the need to give a lifetime guarantee to our operations? The orthopedic surgeons give a 5–10 year warranty on the joints they replace and that is still considered a success.’ I have been reflecting on that provocative statement ever since. I believe our need to provide a lifetime guarantee of our work comes from our general surgical background. It is true that we guarantee no further attacks of biliary colic or appendicitis once we perform a cholecystectomy or appendectomy. Yet in our oncology work, we rarely provide a lifetime warrantee for disease-free survival at the time of informed consent. So instead of debating which & Janice L. Pasieka Janice.pasieka@albertahealthservices.ca

Primary Hepatic Gastrinoma Causing Zollinger-Ellison Syndrome: A Rare and Challenging Diagnosis

The majority of gastrinomas causing Zollinger-Ellison syndrome (ZES) are located in the duodenum or the pancreas. Primary hepatic gastrinomas (PHG) are extremely rare and difficult to diagnose because the liver is the commonest site of metastatic disease and gastrinomas can be very small. Furthermore, gastrinomas are typically slow-growing thus a missed, occult primary tumour may not become evident for many years. The diagnosis of PHG is therefore dependent on a careful search for a primary and long-term biochemical follow-up following curative hepatic resection. We report a case of a 7 cm PHG in a 48 year old man with ZES. Preoperatively, both a basal and stimulated gastrin levels were elevated. Surgical exploration including intraoperative ultrasound and duodenotomy, failed to reveal a primary. Patient underwent a right hepatectomy. Yearly, gastrin and secretin stimulation tests remain normal 6 years following surgery. He remains symptom free off all medication. An additional 26 cases of PHG were found. Including this case, 21 had at least 1 year follow-up, however only eight had greater than 5 years (median 24 months). Post-op gastrin levels were reported in 25, however provocative testing was done in only 10. Persistence and recurrence occurred in one and four, respectively. PHG causing ZES is extremely rare. Although the current literature claims to include 26 additional cases of PHG, without a thorough search for the primary and long-term follow-up data including provocative testing, this diagnosis remains a challenge.

Metastatic midgut carcinoid to the heart demonstrated on cardiac magnetic resonance imaging.

A 53-year-old man presented with vague abdominal cramps, pain, diarrhea, and increasing weight loss. He underwent colonoscopy and an abdominal computed tomography scan that demonstrated a mass in the cecum and liver lesions. At laparotomy, peritoneal seeding and liver metastases were found. The pathology revealed a well-differentiated neuroendocrine carcinoma (NET) arising from multiple small bowel tumors. On assessment in a multidisciplinary NET clinic, he had a classic type 3 carcinoid flush. There was a loud 3/6 holosystolic murmur at the lower left sternal border, increasing with inspiration. He had an elevated u5-hydroxyindoleacetic acid, 118 mol/L (normal 41) and an elevated chromogranin A 290 ng/mL (normal, 6–39). A magnetic resonance imaging (MRI) scan of abdomen demonstrated multiple hypervascular liver lesions and retroperitoneal lymph node enlargement. Both his metaiodo-benzylguanidine and octreotide scans (Fig. 1) confirmed multiple liver lesions, a lesion in the left anterior chest lesion. An echocardiogram demonstrated a cardiac mass arising from the right side of the ventricular septum that did not interfere with ventricular flow and moderate tricuspid regurgitation consistent with carcinoid heart disease. A cardiac MRI scan (Fig. 2) demonstrating a 4.1 4.1 cm mass arising from the interventricular septum and protruding into the right ventricle. Patient was placed on both short-acting and long-acting (LAR) somatostatin analogue. He underwent 3 cycles of I metaiodo-benzylguanidine therapy (4443 MGq each cycle), before reassessment. Eighteen months after his presentation, he is symptomatically controlled on 30 mg of LAR, and his cardiac examination is unchanged. To our knowledge, this is the second reported case of carcinoid metastases to the heart seen on cardiac MRI imaging. In contrast to the Puvaneneswary et al case, this metastasis is myocardial in origin and not arising from the pericardium. Metastatic tumors to the heart are relatively uncommon and are usually associated with carcinomas of the lung, breast, and melanomas. Since 1985 when the first report of myocardial metastases from NET was reported, there have only been 26 reported cases in the literature. Pandya et al reported 11 patients with myocardial metastases, in which the right ventricle was involved in 40%, the left ventricle in 53%, and the ventricular septum in 7%. Cardiovascular MRI and echocardiography are complimentary noninvasive methods for the diagnosis and follow-up of carcinoid heart disease. MRI has excellent tissue characterization ability and provides delineation of relative anatomy. The temporal resolution of echocardiography is, at present, the best technique for the interrogation of most valvular disease. Typically, carcinoid heart disease is characterized by plaque-like deposits and fibrous on the endocardium, resulting in degeneration of the valve leaflets. Bastarrika et al recently reported a case of carcinoid valvular heart disease diagnosis with cardiac MRI. They felt that cardiac MRI better defined their patient’s pulmonary valve disease compared with transesophageal echocardiogram and may, in the future, be the diagnostic imaging of choice in patients with carcinoid heart disease. It is, therefore, conceivable that more patients will be found to have metastatic myocardial disease of neuroendocrine origin as this technology becomes more readily available.