Métodos de diagnóstico de laboratorio e imagenológicos en el síndrome de Zollinger-Ellison

RESUMEN Introducción: el síndrome de Zollinger - Ellison es un tumor neuroendocrino que produce hipersecreción de ácido gástrico y úlcera péptica. Por lo que se realizó la revisión con el objetivo de describir los principales métodos diagnósticos de laboratorio e imagenológicos en el síndrome de Zollinger-Ellison. Desarrollo: se realizó una revisión bibliográfica con los descriptores en español e inglés "síndrome de Zollinger-Ellison", "tumor neuroendocrino" y gastrinoma, sacados de los descriptores en ciencias de la salud (DeCS/MeSH), en las bases de datos Google Académico, SciELO y National Library of Medicine. Como resultados se obtuvo que los métodos de laboratorio son la gastrina sérica basal en ayunas, la cual no es confiable debido a su alteración en diferentes enfermedades, el pH gástrico, excluye hipergastrinemias secundarias, y la secreción gástrica ácida basal, que diferencia las formas de hipergastrinemia. Estos análisis de laboratorio son complementarios entre sí, y para su realización se debe suspender la toma de los inhibidores de la bomba de protones. Otros estudios son la prueba de estimulación por secretina, que confirma la hipergastrinemia, y la prueba de estimulación por calcio, que diagnostica tumores > 1 mm que expresan receptores de calcio. Los métodos imagenológicos son fundamentales para la localización del tumor. La primera técnica de imagen que se debe realizar debido a su alta sensibilidad y especificidad es la gammagrafía con 111In-octreótido, esta localiza tumores no detectados con otras exploraciones y permite realizar el diagnóstico diferencial con lesiones hipervascularizadas. Conclusiones: el síndrome de Zollinger-Ellison requiere para un diagnóstico certero la utilización de métodos de laboratorio y de imagen novedosos.

ABSTRACT Introduction: Zollinger-Ellison syndrome is a neuroendocrine tumor that produces hypersecretion of gastric acid and peptic ulcer. Therefore, the review was carried out with the objective of describing the main laboratory and imaging diagnostic methods in Zollinger-Ellison syndrome. Development: a bibliographic review was carried out with the descriptors in Spanish and English "Zollinger-Ellison syndrome", "neuroendocrine tumor" and gastrinoma, taken from the descriptors in health sciences (DeCS / MeSH), in Google databases. Academic, SciELO and National Library of Medicine. As results, it was obtained that the laboratory methods are fasting basal serum gastrin, which is not reliable due to its alteration in different diseases, gastric pH, excludes secondary hypergastrinemias, and basal acid gastric secretion, which differentiates the forms of hypergastrinemia. These laboratory tests are complementary to each other, and to perform them, the intake of proton pump inhibitors must be suspended. Other tests include the secretin stimulation test, which confirms hypergastrinemia, and the calcium stimulation test, which diagnoses tumors >1 mm that express calcium receptors. Imaging methods are essential for tumor localization. The first imaging technique to be performed due to its high sensitivity and specificity is 111In-octreotide scintigraphy, which locates tumors not detected with other examinations and allows differential diagnosis with hypervascularized lesions. Conclusions: Zollinger-Ellison syndrome requires the use of novel laboratory and imaging methods for an accurate diagnosis.

RESUMO Introdução: a síndrome de Zollinger-Ellison é um tumor neuroendócrino que produz hipersecreção de ácido gástrico e úlcera péptica. Portanto, a revisão foi realizada com o objetivo de descrever os principais métodos de diagnóstico laboratorial e de imagem na síndrome de Zollinger-Ellison. Desenvolvimento: foi realizada revisão bibliográfica com os descritores em espanhol e inglês "Síndrome de Zollinger-Ellison", "tumor neuroendócrino" e gastrinoma, retirados dos descritores em ciências da saúde (DeCS/MeSH), nas bases de dados do Google. Acadêmico, SciELO e Biblioteca Nacional de Medicina. Como resultados, obteve-se que os métodos laboratoriais são a gastrina sérica basal em jejum, o que não é confiável devido à sua alteração em diferentes doenças, pH gástrico, exclui hipergastrinemias secundárias, e secreção gástrica ácida basal, o que diferencia as formas de hipergastrinemia. Esses exames laboratoriais são complementares entre si e, para realizá-los, deve-se suspender a ingestão de inibidores da bomba de prótons. Outros exames incluem o teste de estimulação de secretina, que confirma a hipergastrinemia, e o teste de estimulação de cálcio, que diagnostica tumores >1 mm que expressam receptores de cálcio. Os métodos de imagem são essenciais para a localização do tumor. A primeira técnica de imagem a ser realizada devido à sua alta sensibilidade e especificidade é a cintilografia com 111In-octreotide, que localiza tumores não detectados com outros exames e permite o diagnóstico diferencial com lesões hipervascularizadas. Conclusões: a síndrome de Zollinger-Ellison requer o uso de novos métodos laboratoriais e de imagem para um diagnóstico preciso.

Gastrinoma primario de ganglio linfático

Los gastrinomas son tumores neuroendocrinos localizados generalmente en duodeno y páncreas, en el contexto de una neoplasia endocrina múltiple y configurando un síndrome de Zollinger-Ellison. La localización de este tipo de tumor en ganglios linfáticos es extremadamente inusual y su diagnóstico precoz constituye un verdadero reto para poder instaurar un tratamiento adecuado y manejar las complicaciones que estos conllevan. Se presenta el caso de un paciente varón de 64 años con un gastrinoma de ganglio linfático y cuya extirpación quirúrgica resultó en la remisión inmediata del cuadro clínico del paciente.

Gastrinomas are neuroendocrine tumors usually located in the duodenum and pancreas, in the context of a Multiple Endocrine Neoplasm and forming a Zollinger-Ellison syndrome. The location of this type of lymph node tumor is extremely unusual and its early diagnosis constitutes a real challenge to be able to establish an adequate treatment and manage the complications that these entail. We present the case of a 64-year-old male patient with a lymph node gastrinoma and whose surgical removal resulted in the immediate remission of the patient's symptoms.

Neuroendocrine neoplasms associated with chronic diarrhea in children / 国际儿科学杂志

Tumor-related diarrhea is a rare cause of chronic diarrhea in children, which is usually one of the clinical manifestations of specific functional syndrome of neuroendocrine neoplasms.Diarrhea may appear as the initial symptom or accompany symptom of disease progression, and it is generally relieved or cured after surgical resection.The present review mainly introduces several common neuroendocrine neoplasms which cause chronic diarrhea in children, and summarizes their different diarrhea features and mechanisms, as well as key points in diagnosis and treatment, in order to improve the rate of early diagnosis and prognosis of children.

Comparison of clinical characteristics between sporadic gastrinoma and multiple endocrine neoplasia type 1-related gastrinoma / 中华胃肠外科杂志

Objective: To compare clinical characteristics of sporadic gastrinoma and multiple endocrine neoplasia type 1 (MEN1)-related gastrinoma. Methods: A retrospective cohort study was conducted. Patients with clinical manifestations of Zollinger-Ellison syndrome, pathological diagnosis as neuroendocrine neoplasm (NEN) and complete clinical and follow-up data were enrolled. Patients with only high gastric acid secretion but without evidence of NEN, or with other concurrent non-NEN tumors were excluded. According to the above criteria, the clinicopathological data of 52 cases of gastrinoma diagnosed from April 2003 to December 2020 in the First Affiliated Hospital, Sun Yat-sen University, were collected. Patients who met the diagnostic criteria of gastrinoma and met one of the following conditions were diagnosed as MEN1-related gastrinoma: (1) the presence of pathogenic mutations in the MEN1 gene confirmed by genetic testing; (2) NENs involving two or more endocrine glands, namely, pituitary, parathyroid, thymic, pancreatic, and adrenal NENs; (3) NEN and at least one first-degree relatives diagnosed as MEN1. The remaining gastrinomas were defined as sporadic gastrinoma. Student's t test and chi-square test were used for statistical analysis. Clinicopathological characteristics, endoscopic findings, imaging characteristics, treatment, and prognosis of sporadic and MEN1-related gastrinoma were compared. Results: Among 52 patients with gastrinoma, 33 were sporadic gastrinoma and 19 were MEN1-related gastrinoma. The common symptoms of both sporadic and MEN1-related gastrinomas were diarrhea (24/33, 72.7%; 17/19, 89.5%) and abdominal pain (19/33, 57.6%; 9/19, 47.4%). Compared with sporadic gastrinoma, MEN1-related gastrinoma needed longer time for diagnosis [(7.4±4.9) years vs. (3.9±5.2) years, t=-2.355, P=0.022), were more likely multiple tumors [47.4% (9/19) vs. 15.2% (5/33), χ(2)=6.361, P=0.012], had smaller diameter [(1.7±1.0) cm vs. (3.1±1.8) cm, t=2.942, P=0.005), presented the lower tumor grade [G1: 83.3% (15/18) vs. 39.4% (13/33); G2: 11.1% (2/18) vs. 54.5% (18/33); G3: 5.6% (1/18) vs. 6.1% (2/33), Z=-2.766, P=0.006], were less likely to have serum gastrin which was 10 times higher than normal [11.8% (2/17) vs. 56.0% (14/33), χ(2)=8.396, P=0.004], had higher probability of complication with type 2 gastric neuroendocrine tumors (g-NET) [31.6% (6/19) vs. 3.0%(1/33), χ(2)=6.163, P=0.013], and had lower rate of liver metastasis [21.1% (4/19) vs. 51.5% (17/33), χ(2)=4.648, P=0.031). There was no obvious difference between sporadic gastrinomas and MEN1-related gastrinomas in endoscopic findings. Both types presented enlarged and swollen gastric mucosa under the stimulation of high gastric acid, and multiple ulcers in the stomach and duodenum could be seen. Gastrinoma with type 2 g-NET presented multiple polypoid raised lesions in the fundus and body of the stomach. (68)Ga-SSR-PET/CT scan had a 100% detection rate for both types while (18)F-FDG-PET/CT scan had a higher detection rate for sporadic gastrinoma compared with MEN1-related gastrinoma [57.9% (11/19) vs. 20.0% (3/15), χ(2)=4.970, P=0.026]. Among the patients with sporadic gastrinoma, 19 received surgical treatment, 1 underwent endoscopic submucosal dissection, 8 underwent transcatheter arterial embolization (TAE), and 5 underwent surgery combined with TAE. Among patients with MEN1-related gastrinoma, 13 received surgical treatment, and the other 6 received conservative treatment. The median follow-up of all the patients was 21.5 (1-129) months, and the 5-year survival rate was 88.4%. The 5-year survival rate of patients with sporadic and MEN1-related gastrinomas was 89.5% and 80.0% respectively (P=0.949). The 5-year survival rate of patients with and without liver metastasis was 76.2% vs. 100%, respectively (P=0.061). Conclusions: Compared with sporadic gastrinoma, MEN1-related gastrinoma has longer diagnosis delay, smaller tumor diameter, lower tumor grading, lower risk of liver metastasis, and is more likely to complicate with type 2 g-NET, while there is no difference in survival between the two tumor types.

Zollinger-ellison syndrome. case report

ABSTRACT Introduction: The Zollinger-Ellison syndrome (ZES) is a pathology caused by a neuroendocrine tumor, usually located in the pancreas or the duodenum, which is characterized by elevated levels of gastrin, resulting in an excessive production of gastric acid. Case presentation: A 42-year-old female patient with a history of longstanding peptic ulcer disease, who consulted due to persistent epigastric pain, melena and signs of peritoneal irritation. Perforated peptic ulcer was suspected, requiring emergency surgical intervention. Subsequently, a tumor lesion in the head of the pancreas was documented and managed with Whipple procedure. The pathology results reported a tumor suggestive of neuroendocrine neoplasm. Discussion: The Zollinger-Ellison syndrome occurs in 0.1 to 3 people per 1 000 000 inhabitants worldwide and is predominant in women between 20 and 50 years of age. It usually appears as a refractory acid-peptic disease or as a complication of gastric acid hypersecretion. Medical therapy is the standard management, being proton pump inhibitors (PPI) the most effective option. Surgery is recommended for sporadic ZES. Conclusions: ZES has a low incidence rate. It is rarely considered in the differential diagnosis of chronic epigastric pain and high clinical suspicion is required to achieve adequate management. This article is highly relevant as it presents a confirmed clinical case of ZES in Colombia, highlighting the importance of producing local scientific literature to improve the diagnosis and treatment of this pathology.

RESUMEN Introducción. El síndrome de Zollinger-Ellison (SZE) es una patología producida por un tumor neuroendocrino habitualmente localizado a nivel duodenal o pancreático, el cual produce niveles elevados de gastrina, derivando en hipersecreción de ácido gástrico. Presentación del caso. Paciente femenino de 42 años con antecedente de enfermedad ulceropéptica de larga data, quién consulta por epigastralgia persistente y deposiciones melénicas y presenta signos de irritación peritoneal. Se sospecha una ulcera péptica perforada, requiriendo intervención quirúrgica de urgencia. Posteriormente se documenta una lesión tumoral en la cabeza del páncreas, manejada con cirugía de Whipple; en el reporte de patología se detecta un tumor sugestivo de neoplasia neuroendocrina. Discusión. El SZE se presenta en 0.1-3 personas por cada 1 000 000 de habitantes a nivel mundial, predominantemente en mujeres entre 20 y 50 años de edad. Suele debutar como enfermedad ácido-péptica refractaria o por complicaciones de la hipersecreción gástrica. La terapia médica es el manejo estándar, siendo la más efectiva la que involucra inhibidores de la bomba de protones. En SZE esporádico está recomendada la cirugía. Conclusiones. El SZE tiene una incidencia baja, raramente se considera en el diagnóstico diferencial de epigastralgia crónica y se requiere alta sospecha clínica para lograr un manejo adecuado. Este artículo es valioso al presentar un caso clínico confirmado de SZE en Colombia, destacando la importancia de producir bibliografía científica local para mejorar el diagnóstico y tratamiento de esta patología.

A Study of Propeller Flaps for the Reconstruction of Soft Tissue Defects of Lower Limbs

Introduction: Reconstruction of simple or complex woundsof the lower one third limb is a challenge for reconstructivesurgeons. Various local Fasciocutaneous, Musculocutaneousand free flaps have been described for reconstruction withtheir own merits and demerits. The perforator-based propellerflaps, harvested around a perforator pedicle by means of therotation of skin paddle, up to 1800 are now currently usedtechnique to cover the tissue loss in the lower extremities.There is no sacrifice of major blood vessel. The aim of thisstudy was to assess the versatility and reliability of the use ofpropeller flaps for leg defectsMaterial and Methods: 20 Patients with traumatic lower limbdefects of various sites and sizes treated in the Department ofPlastic Surgery, Gandhi Hospital, Secunderabad, during theperiod 2010 – 2013 were included in the study. A suitablesized perforator close to the defect was identified by hand heldHunt Leigh Doppler in all the patients.Results: Of the 20 patients 90% were males and commonestaetiology was trauma, 65% of the defects were in lower thirdlimb and our success rate is 70%.Conclusions: The perforator-based propeller flap adds newarmamentarium of reconstructive surgeons. This is a simpleversatile technique and is less time consuming with no donorsite morbidity. It is ideal for reconstruction of small-to mediumsize defects of distal leg and ankle region with good cosmetic,excellent colour, match

Malignant pancreatic gastrinoma in a maned wolf (Chrysocyon brachyurus): case report / Gastrinoma pancreático maligno em lobo-guará (Chrysocyon brachyurus): relato de caso

A captive 12-year-old female maned wolf (Chrysocyon brachyurus), previously diagnosed with visceral leishmaniasis, developed severe myiasis in the right ear, followed by prostration and death. A firm solid nodule, measuring 1 x 3cm, was grossly observed in the pancreas. Histologically, there was neoplastic proliferation in the pancreas and pancreatic lymph node. Neoplastic cells had a neuroendocrine pattern, and were positive for gastrin and pancreatic polypeptide by immunohistochemistry. The wolf had also ulcerative gastritis. To the best of our knowledge is the first reported case gastrinoma in this species.(AU)

Uma fêmea lobo-guará de cativeiro (Chrysocyon brachyurus), diagnosticada previamente com leishmaniose visceral, desenvolveu miíase grave na orelha direita, seguida por prostação e morte. Um nódulo sólido, firme e medindo 1 x 3cm, foi macroscopicamente observado no pâncreas. Histologicamente, observou-se proliferação neoplásica no pâncreas e linfonodo pancreático. As células neoplásicas tinham um padrão neuroendócrino e foram positivas para gastrina e polipeptideo pancreático por imuno-histoquímica. A loba tinha também gastrite ulcerativa. Este é o primeiro caso descrito de gastrinoma nessa espécie.(AU)

Incidental Detection of Parathyroid Adenoma on Somatostatin Receptor PET/CT and Incremental Role of ¹⁸F-Fluorocholine PET/CT in MEN1 Syndrome / 대한핵의학회잡지

Multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by combined occurrence of tumors of endocrine glands including the parathyroid, the pancreatic islet cells, and the anterior pituitary gland. Parathyroid involvement is the most common manifestation and usually the first clinical involvement inMEN1 syndrome, followed by gastroentero-pancreatic neuroendocrine tumors (NETs). Here we present a case where the patient initially presented with metastatic gastric NET and a single parathyroid adenoma was detected incidentally on ⁶⁸Ga-DOTANOC PET/CT done as part of post ¹⁷⁷Lu-DOTATATE therapy (PRRT) follow-up. Further ¹⁸F-fluorocholine PET/CT showed four adenomas for which the patient subsequently underwent subtotal parathyroidectomy.

A Case of Multiple Endocrine Neoplasia Type 1 in Type 2 Diabetes Mellitus with Poor Glycemic Control / 임상당뇨병

The primary causes of uncontrolled diabetes are poor life-style, infection, ischemic heart disease and inappropriate usage of oral anti-diabetic agents and insulin. Supplementary causes are stroke, acute pancreatitis and endocrine diseases. Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant syndrome characterized by primary hyperparathyroidism, pituitary neoplasia, and foregut lineage neuroendocrine tumors, and is associated with increased glucose levels. We present a case of a 69-year-old woman who had polyuria, polydipsia, weight loss and hyperglycemia over 6 months. She had hypertrophy of the face, hand, and foot, and active bleeding and large folds were observed in the stomach and duodenum upon esophagogastroduodenoscopy. She also had high levels of IGF-1 and gastrin and got the failure of growth hormone suppression after an oral glucose load (75 g). These findings suggested a diagnosis of acromegaly and gastrinoma, which was clinically diagnosed along with MEN 1. The patient improved glycemic control and symptoms after being treated with somatostatin analogues and insulin therapy over a 5-month follow-up period. Here, we report a case of MEN 1 in type 2 diabetes mellitus with a poorly controlled blood glucose level. Clinicians should consider endocrine disease in patients with poor glycemic control in diabetes.

Síndrome de Zollinger-Ellison: revisión del conocimiento actual / Zollinger-Ellison syndrome: review of current knowledge

El síndrome de Zollinger-Ellison se caracteriza por la presencia de úlceras pépticas resistentes al tratamiento que se deben a la hipersecreción ectópica de gastrina por un tumor neuroendocrino, que es el gastrinoma y que resulta en la hipersecreción de ácido clorhídrico en el estómago. Este síndrome se presenta en forma esporádica y también se asocia al síndrome de neoplasia neuroendocrina múltiple de tipo 1. Se describen ambas presentaciones clínicas, así como también la fisiopatología, el diagnóstico, el estudio, el tratamiento y el pronóstico, enfatizando en los detalles técnicos de la cirugía. El pronóstico de los gastrinomas cuando son identificados precozmente es bueno, aun en aquellos casos malignos, por lo que la sospecha clínica asociada al estudio específico y al tratamiento de estos pacientes es fundamental. Dada la tecnología diagnóstica disponible en la actualidad, la identificación de estos tumores será cada vez más frecuente, por lo que el conocimiento de los detalles esenciales para su tratamiento es importante para el cirujano.

Zollinger-Ellison syndrome is characterized by peptic ulcers refractory to treatment secondary to ectopic gastrin hypersecretion by a neuroendocrine tumor called gastrinoma resulting in gastric hydrochloride acid hypersecretion. This syndrome occurs sporadically and is also associated to Multiple Neuroendocrine Neoplasia type 1. The present article describes their clinical presentations, as well as their pathophysiology, diagnosis, study, treatment and prognosis, emphasizing the surgical technical details. Early diagnosis of gastrinoma carries a good prognosis, even in those malignant cases. Consequently, clinical suspicion associated to specific study leading to diagnosis and treatment is fundamental for these patients. Due to the available current technology, the diagnosis of these tumors should be more common, as a consequence the knowledge of important details within their management is important for the surgeon.

Síndrome de zolinger - Elison / Syndrome of Zolinger - Elison

Resumen:El síndrome de Zollinger - Ellison es una endocrinopatía que fue descrita en 1955 por los doctores Robert Zollinger y Edwin Ellison, quienes propusieron la triada diagnóstica que incluye hipersecreción gástrica ácida, úlcera péptica y gastrinoma. Esta enfermedad predomina en mujeres entre los 50 y 60 años de edad. Según su etiología, este síndrome se clasifica en una forma esporádica o asociada a neoplasia endocrina múltiple tipo 1 (NEM - 1).Más de la mitad de los gastrinomas se localizan en la pared duodenal, el páncreas es la segunda ubicación en frecuencia. Existen localizaciones ectópicas en ovario, mesenterio, hígado y ducto biliar. A nivel histopatológico se encuentran células tumorales redondas, con núcleos pequeños y nucléolos prominentes. La hipersecreción ácida gástrica está asociada a un defecto en la inhibición del retrocontrol negativo de la somatostatina sobre las células G antrales productoras de gastrina. Clínicamente, los pacientes manifiestan dolor abdominal, diarrea, pirosis, náuseas y vómitos; relacionados principalmente a la formación de úlceras pépticas. El diagnóstico debe incluir una medición en los niveles séricos de gastrina y valores de pH gástrico. El tratamiento de primera línea es la terapia antisecretora, principalmente con inhibidores de la bomba de protones. Los estudios de imágenes son deutilidad para detectar metástasis y evaluar la enfermedad quirúrgicamente resecable. Se debe hacer diagnóstico diferencial con otros tumores neuroendocrinos y causas de hipergastrinemia.

Abstract:Zollinger - Ellison syndrome is an endocrinopathy that was first described in 1955 by doctors Robert Zollinger and Edwin Ellison, who proposed the diagnostic triad that includes gastric acid hypersecretion, peptic ulcer and gastrinoma. This disease predominates in women between 50 and 60 years old. Based on the etiology, the syndrome is classified in sporadic or associated with multiple endocrine neoplasia type 1 (NEM - 1). Over half of gastrinomas are located in the duodenal wall, the pancreas is the second frequency location. There are ectopic locations, such as ovary, mesentery, liver and bile duct. Round cells, small nuclei and prominent nucleoli, are the main hispathologycal characteristics. Gastric acid hypersecretion is associated with a defect in the negative feedback inhibition of somatostatin on G antral gastrin-producing cells. Clinically, patients present abdominal pain, diarrhea, heartburn, nausea and vomiting; primarily related to the development of peptic ulcers. Diagnosis includes a measurement in serum gastrin levels and gastric pH values. The first line treatment is the antisecretory therapy, primarily proton-pump inhibitor. Imaging studies are useful to detect metastases and evaluate the surgically resectable disease. Neuroendocrine tumors and hypergastrinemia causes are the main differential diagnoses, the clinician should consider.

Synchronous Peripancreatic Lymph Node Gastrinoma and Gastric Neuroendocrine Tumor Type 2

A 34-year-old man was referred to our hospital with gastric polypoid lesions and biopsy-confirmed neuroendocrine tumor (NET). Computed tomography (CT) revealed a 3×3.5×8-cm retroperitoneal mass behind the pancreas, with multiple hepatic metastases. His serum gastrin level was elevated to 1,396 pg/mL. We performed a wedge resection of the stomach, a right hemi-hepatectomy, and a retroperitoneal mass excision. After careful review of the clinical, radiological, histopathological, and immunohistochemical findings, peripancreatic gastrinoma, and synchronous gastric NET were ultimately diagnosed. We reviewed a CT scan that had been performed 6 years previously after surgery for a duodenal perforation. There was no evidence of gastric or hepatic lesions, but the retroperitoneal mass was present at the same site. Had gastrinoma been detected earlier, our patient could have been cured using less invasive treatment. This case demonstrates how important it is to consider Zollinger-Ellison syndrome in patients with a recurrent or aggressive ulcer.

A Case of Zollinger-Ellison Syndrome in Multiple Endocrine Neoplasia Type 1 with Urolithiasis as the Initial Presentation / 대한소화기학회지

Zollinger-Ellison syndrome (ZES) is characterized by gastrinoma and resultant hypergastrinemia, which leads to recurrent peptic ulcers. Because gastrinoma is the most common pancreatic endocrine tumor seen in multiple endocrine neoplasia type I (MEN 1), the possibility of gastrinoma should be investigated carefully when patients exhibit symptoms associated with hormonal changes. Ureteral stones associated with hyperparathyroidism in the early course of MEN 1 are known to be its most common clinical manifestation; appropriate evaluation and close follow-up of patients with hypercalcemic urolithiasis can lead to an early diagnosis of gastrinoma. We report a patient with ZES associated with MEN 1, and urolithiasis as the presenting entity. A 51-year-old man visited the emergency department with recurrent epigastric pain. He had a history of calcium urinary stone 3 years ago, and 2 years later he had 2 operations for multiple jejunal ulcer perforations; these surgeries were 9 months apart. He was taking intermittent courses of antiulcer medication. Multiple peripancreatic nodular masses, a hepatic metastasis, parathyroid hyperplasia, and a pituitary microadenoma were confirmed by multimodal imaging studies. We diagnosed ZES with MEN 1 and performed sequential surgical excision of the gastrinomas and the parathyroid adenoma. The patient received octreotide injection therapy and close follow-up.

Clinical, pathologic and endoscopic ultrasound characteristics of pancreatic neuroendocrine tumors / 中华胰腺病杂志

Objective To investigate the clinical,pathologic and endoscopic ultrasound characteristics of pancreatic neuroendocrine tumors (PNETs).Methods Clinical data of 24 consecutive patients of PNETs who were admitted between January 2002 and January 2011 were reviewed.Results Among these 24 patients,19 were diagnosed to have insulinomas,1 was malignant insulinoma,2 were gastrinomas,and 2 were glucagonomas.Eighteen (75％) cases of PNETs were functional PNETs,and 6 (25％) were nonfunctional PNETs.The mean age of the patients was (42 ± 14) years old ranging from 19 ～ 64 years old,and the percentage of male patient was 33.3％.The main symptoms of insulinomas were intermittent abdominal pain or discomfort,and the main manifestations of glucagonomas were weight loss,skin migratory erythema; and the main symptoms of gastrinomas were diarrhea,vomiting with large amounts of water-like liquid.The detection rate of CT was 86.7％ (13/15),and the detection rate of EUS was 100％ (15/15),but PET-CT detected only 40％ of tumors (2/5).The endoscopic ultrasound characteristics of PNETs were circular or oval hypoechoic mass,and the volume was small with clear boundary and homogeneous echo.There was no enlarged lymph node,and liquid was detected in big tumor.Twenty-two patients received operation and 2 patients did not.PNETs expressed CgA and Syn protein.All patients of PNETs were alive with 7 to 80 months follow-up.Conclusions The clinical characteristics of PNETs were unique.EUS has a high accuracy for detecting and localizing PNETs.The surgical method is similar to that of pancreatic cancer,and the prognosis is relatively good.

Tumores neuroendocrinos del páncreas / Pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors are infrequent and slow-growing neoplasms. They are classified basedon their clinical presentation as functioning and nonfunctioning tumors. The most common functionaltumors are the insulinoma and gastrinoma. They can be sporadic or be part of hereditary forms as MEN-1.The diagnosis is based on the detection of the specific clinical syndrome in association of high levels of the substance secreted by the tumor and conventional imaging studies or others such as stimulation tests, somatostatin receptor scintigraphy and endoscopic ultrasound. In general, these tumors have a better prognosis than the pancreatic adenocarcinoma and they can show metastasis to the liver and infrequently, in bones. The treatment can be managed medically diminishing the inappropriate secretion of the substances by the tumor using, for example, the somatostatin analogs. Surgery should be always considered, especially in case of insulinomas, small non-functioning tumors, and small gastrinomas that can be managed with surgery enucleation. More advanced resective surgery, such as Whipple resection, are not routinely recommended and they should be limited to selected patients. In advanced tumors, there are other treatment alternatives, for example, hepatic resection, radiofrequency, chemotherapy and new agents such as sunitinib and everolimus.

Los tumores neuroendocrinos pancreáticos son infrecuentes y de crecimiento lento. Se clasifican en tumores funcionantes o no funcionantes (TNEP-NF), de acuerdo a la presentación clínica. Los tumores funcionantes más frecuentes son los insulinomas y los gastrinomas. Pueden ocurrir en forma esporádica o asociados a síndromes hereditarios como la NEM- 1, entre otros. El diagnóstico se basa en la detección del síndrome clínico específico asociado a la demostración de niveles elevados de la sustancia secretada y exámenes imagenológicos convencionales u otros más específicos como de estimulación, cintigrafía de receptores de somatostatina y endosonografía. En general, tienen mejor pronóstico que los adenocarcinomas pancreáticos y pueden dar metástasis hepáticas y con menor frecuencia, óseas. El tratamiento puede ser médico disminuyendo la secreción inapropiada de las sustancias producidas por el tumor como los análogos de somatostatina. La cirugía siempre debe ser considerada, especialmente en caso de insulinomas, pequeños TNEP-NF, y gastrinomas pequeños, que pueden ser tratados con enucleación quirúrgica. Las cirugías resectivas más avanzadas, como la operación de Whipple no están recomendadas en forma rutinaria y sólo deben ser utilizadas en pacientes seleccionados. En casos de tumores avanzados, existen alternativas de tratamiento, como la resección hepática, radiofrecuencia, quimioterapia, y terapia con nuevos agentes en estudio como el sunitinib y everolimus.

Tumores neuroendocrinos gastroenteropancreáticos / Gastroenteropancreatic neuroendocrine tumors (GEP-NETS)

Los tumores neuroendocrinos gastroenteropancreáticos son neoplasias raras distribuidas a lo largo del tubo digestivo y poseen características peculiares, como la captación de sales de plata, la expresión de marcadores de célula neuroendocrina y los gránulos secretorios de contenido hormonal. Según su tamaño, localización anatómica y la presencia de metástasis, estos tumores debutan con distintas características clínicas y pronóstico. El diagnóstico temprano, que requiere de un alto grado de sospecha y una confirmación con estudios especializados, resulta invaluable para tratar estas lesiones a tiempo y aumentar la sobrevida de los pacientes. El tratamiento quirúrgico es la herramienta de primera mano, y otras terapias médicas ayudan a mejorar los síntomas y la calidad de vida de aquellos pacientes con lesiones irresecables. En esta revisión, se tratan los aspectos más relevantes en cuanto a la clasificación, morfología, localización, diagnóstico y tratamiento de estas neoplasias gastrointestinales, y al final, se expone la única experiencia colombiana sobre la epidemiología y el manejo de los tumores neuroendocrinos.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) are rare neoplasms which can occur anywhere in the gastrointestinal tract. Their particular characteristics include uptake of silver salts, neuroendocrine cell marker expression and hormonal secretory granules. Depending on their size, anatomical location and upon whether or not metastasis has occurred, these tumors can show different clinical patterns and have different prognoses. Early diagnosis is essential for treating these lesions and improving the patients’ prognoses, but it requires a high degree of suspicion and confirmation by special testing. Surgical treatment is the first choice, but other medical therapy can be helpful for patients who have unresectable disease. This review presents the most relevant aspects of classification, morphology, methods of locating tumors, diagnosis and treatment of GEP-NETS. It presents only the Colombian experience in the epidemiology and management of these tumors.

Síndrome de Zollinger Ellison secundario a gastrinoma duodenal: reporte de un caso y revisión de la literatura / Zollinger Ellison syndrome secondary to duodenal gastrinoma: a case report and literature review

El síndrome de Zollinger Ellison es una entidad producto de un tumor neuroendocrino hipersecretor de gastrina, que genera acidez gástrica exagerada. Entre el 60 a 90% de los casos se comparta de forma maligna, se observan nódulos metastásicos en 50 a 67% de los casos, y se localizan principalmente en el denominado triángulos de los gastrinomas. Los métodos de imagen convencionales poseen poca sensibilidad en la detección de éstas lesiones, sobre todo para las menores a 1 cm. La endosonografía conjunto a la cintilografía de receptores de Somatostatina, son los métodos de imagen estándar de oro para diagnosticar estas lesiones. Presentamos el caso de un paciente masculino de 57 años, que consultó con pancreatitis aguda, enfermedad ulceropéptica y diarrea, a quien se detectó y estadió una lesión única mediante endosonografía, recibió tratamiento quirúrgico de forma exitosa...

Zollinger-Ellison syndrome is a disorder caused by a gastrin hypersecretory neuroendocrine tumor which produces severe gastric acidity. In 60% to 90% of the cases it`s malignant; metastatic nodules are observed in 50% to 67% of the cases, and are located primarily in the so called Gastrinoma triangle. The conventional imaging methods have poor sensibility in detecting these lesions, especially for those that are less than 1 cm. The endosonography conjoint with the Somatostatin receptors scintillography are the standard imaging gold methods to diagnose these lesions. We report the case of a male 57 years-old patient who came to consult with acute pancreatitis, peptic ulcer disease and diarrhea. By endosonography we detected and staged a single lesion. He received surgical treatment successfully...

A case of Zollinger-Ellison syndrome with MEN-1 / 대한내과학회지

Zollinger-Ellison syndrome (ZES) is a clinical syndrome caused by excessive gastric acid secretion by gastrinoma, characteristically causing peptic disease and/or gastroesophageal reflux disease. Approximately one third of patients with gastrinoma have multiple endocrine neoplasia type 1 (MEN-1). A 56-year-old man was admitted for abdominal pain and diarrhea lasting for 2 weeks. The endoscopic findings revealed severe reflux esophagitis and multiple ulcers at the bulb and second portion of the duodenum. He was diagnosed as ZES based on typical clinical features such as markedly elevated fasting gastrin level (> or =1,263 pg/mL) and findings from a CT scan and somatostatin receptor scan. Pathologic findings after the operation revealed malignant gastrinoma. He was confirmed to have parathyroid adenoma and MEN-1. Despite antisecretory therapy with proton pump inhibitors, an esophageal stricture developed, and we performed esophageal balloon dilatation and stent insertion.

A Case of Multiple Endocrine Neoplasia Type 1 with Primary Liver Gastrinoma

Gastrinoma is the most frequent functional pancreaticoduodenal endocrine tumor in patients with multiple endocrine neoplasia type 1 (MEN 1). Primary hepatic gastrinomas in MEN 1 are very rare, with no previous reports published in the literature. We reported the case of a 39 yr old female patient with a history of repeated peptic ulcers and a hypoglycemia episode. Abdominal CT indicated a well-defined liver mass and a pancreatic head mass. Somatostatin-receptor scintigraphy with [111In] DTPA octeotride demonstrated a strong uptake of the radiotracer in the left lateral segment at the site of the hepatic mass. After operation, immunohistochemical staining was consistent with pancreatic insulinoma and primary hepatic gastrinoma. As the liver is a common site of metastases from gastrinoma, primary liver gastrinoma has not yet been reported with MEN 1. We diagnosed this patient using immunohistochemical studies and treated this patient by hepatic segmentectomy.

A Case of Multiple Endocrine Neoplasia Type 1 Combined with Papillary Thyroid Carcinoma

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature.