Atypical Thymic Carcinoid in a Patient with Zollinger-Ellison Syndrome / 대한흉부외과학회지

Atypical thymic carcinoid is an extremely rare tumor with a poor prognosis. In addition to its known association with multiple endocrine neoplasia type 1, its hallmark characteristics include local invasion and early distant metastasis. In this report, we share our experience treating atypical thymic carcinoid in a patient with Zollinger-Ellison syndrome.

The Effect of H₂ Receptor Antagonist in Acid Inhibition and Its Clinical Efficacy / 대한소화기학회지

The first histamine H₂ receptor antagonists (H₂RAs) were developed in the early 1970s. They played a dominant role in treating peptic ulcer disease and gastroesophageal reflux disease (GERD). H₂RAs block the production of acid by H⁺, K⁺-ATPase at the parietal cells and produce gastric luminal anacidity for varying periods. H₂RAs are highly selective, and they do not affect H₁ receptors. Moreover, they are not anticholinergic agents. Sequential development of H₂RAs, proton pump inhibitors (PPIs), and discovery of Helicobacter pylori infection changed the paradigm of peptic ulcer disease with marked decrease of morbidity and mortality. PPIs are known to be the most effective drugs that are currently available for suppressing gastric acid secretion. Many studies have shown its superiority over H₂RAs as a treatment for acid-related disorders, such as peptic ulcer disease, GERD, and Zollinger-Ellison syndrome. However, other studies have reported that PPIs may not be able to render stomach achlorhydric and have identified a phenomenon of increasing gastric acidity at night in individuals receiving a PPI twice daily. These nocturnal acid breakthrough episodes can be eliminated with an addition of H₂RAs at night. The effectiveness of nighttime dose of H₂RA suggests a major role of histamine in nocturnal acid secretion. H₂RAs reduce secretion of gastric acid, and each H₂RA also has specific effects. For instance, nizitidine alleviates not only symptoms of GERD, but also provokes gastric emptying, resulting in clinical symptom improvement of functional dyspepsia. The aim of this paper was to review the characteristics and role of H₂RAs and assess the future strategy and treatment of upper gastrointestinal disease, including acid related disorders.

Neoplasia endocrina múltiple tipo 1 A propósito de un caso / Multiple endocrine neoplasia type 1 About a case

La neoplasia endocrina múltiple tipo 1 (NEM1) es un raro síndrome hereditario, autosómico dominante, clásicamente caracterizado por tumores en varias glándulas (paratiroides, adenohipófisis e islotes pancreáticos). La prevalencia del NEM1 es de aproximadamente 2 por 100.000 habitantes.El síndrome de Zollinger Ellison (SZE) es una de las 3 neoplasias que forman parte del NEM1 y corresponde al 20 a 60%. A continuación se presenta el caso clínico de un paciente de sexo masculino, 66 años de edad, con cuadro clínico de síndrome de Zollinger Ellison que, en investigación posterior, evidencia alteración funcional de las glándulas paratiroides, cumpliendo criterios diagnósticos de neoplasia endocrina múltiple tipo 1 (NEM1).(AU)

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant hereditary syndrome, classically characterized by the presence of tumors in several glands (parathyroid, anterior pituitary and pancreatic islets) The prevalence of MEN 1 is approximately 2 per 100,000 inhabitants. The Zollinger Ellison syndrome (ZES) is one of the three neoplasias that form part of the MEN 1, and corresponds to 20 to 60%. The clinical case of a 66-year-old male patient, with a clinical of Zollinger Ellison Syndrome, who in a subsequent investigation shows functional abnormality of the parathyroid glands, fulfilling diagnostic criteria of Multiple Endocrine Neoplasia type 1 (NEM1) (AU)

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.

Diagnostic and Treatment Approaches for Refractory Peptic Ulcers

Refractory peptic ulcers are defined as ulcers that do not heal completely after 8 to 12 weeks of standard anti-secretory drug treatment. The most common causes of refractory ulcers are persistent Helicobacter pylori infection and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Simultaneous use of two or more H. pylori diagnostic methods are recommended for increased sensitivity. Serologic tests may be useful for patients currently taking proton pump inhibitors (PPIs) or for suspected false negative results, as they are not affected by PPI use. NSAID use should be discontinued when possible. Platelet cyclooxygenase activity tests can confirm surreptitious use of NSAIDs or aspirin. Cigarette smoking can delay ulcer healing. Therefore, patients who smoke should be encouraged to quit. Zollinger-Ellison syndrome (ZES) is a rare but important cause of refractory gastroduodenal ulcers. Fasting plasma gastrin levels should be checked if ZES is suspected. If an ulcer is refractory despite a full course of standard PPI treatment, the dose should be doubled and administration of another type of PPI considered.

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.

Neuroendocrine Tumor in Upper Gastrointestinal Tract

Gastric neuroendocrine tumor (GNET) is rare, but increasing in incidence. GNET may be classified into three types on the basis of the background pathology. Type I GNET is related to autoimmune atrophic gastritis and hypergastrinemia. Type II is related to multiple endocrine neoplasia (MEN)-1, Zollinger-Ellison syndrome and hypergastrinemia and sporadic Type III is not related to any background pathology. Type I GNETs can be considered as benign tumors with unusual metastases. However, type II may be related to distant metastases, which is also common in type III GNETs. Type I and type II lesions can be treated by endoscopic excision or somatostatin analogues whereas surgical treatment should be considered for type III lesions. Hypergastrinemia is an essential precondition for the evolution of type I and II lesions, but hypergastrinemia alone is not enough for explanation of tumorigenesis. Furthermore, the pathogenesis of type III neuroendocrine tumors is still poorly understood. Despite improvements in our knowledge of GNET pathogenesis in diagnostic approach and treatment, further investigations and large scale clinical studies are warranted.

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 Zollinger-Ellison syndrome: localization of gastrinoma by selective intra-arterial calcium injection / 대한내과학회지

Zollinger-Ellison syndrome is a very rare disease that's caused by tumor having gastrin-producing cells, and this is accompanied by hypergastrinemia leading to gastric acid hypersecretion, peptic ulcer and their complications. A 60-year-old man presented with epigastric pain and soreness he had experienced for 7 days. The endoscopic findings showed reflux esophagitis and multiple active ulcers at the antrum, the duodenal bulb and the 2nd and 3rd portions of the duodenum. The fasting serum gastrin level was markedly elevated above 1,470 pg/mL and this was consistent with the findings of gastrinoma. We confirmed the presence of gastrinoma via the abdomen CT scan and selective intra-arterial calcium injection. This is the first Korean case report of gastrinoma that was localized by selective intra-arterial calcium injection.

Tumor carcinoide gástrico: a propósito de un caso / Gastric carcinoids tumor: with regard to a case

Carcinoides gástricos son tumores raros originados de la células enterocromaffin-like de la mucosa no antral. Sin embargo, la prevalencia es mucho mayor en pacientes con hipergastrinemia, como en la anemia perniciosa, aclorhidria, síndrome de Zollinger-Ellison y estados de baja acidez. La mayoría de estos tumores son de crecimiento lento, con bajo porcentaje de metástasis, en especial hígado y ganglios linfáticos. Los carcinoides gástricos han sido clasificados en tres subtipos, con el fin de determinar el pronóstico y la terapia más adecuada. Presentamos un caso de tumor carcinoide gástrico en un masculino de 28 años que fue manejado en el Hospital San Juan de Dios.

[Primary hepatic carctnoid tumor: a case report]

Primary hepatic carcinoid tumors are extremely rare, and fewer than 60 cases have been reported in the literature. Long-term follow-up is necessary for establishing the primary nature of liver carcinoids. We report a case arising in a young 20 years-man having Zollinger-Ellison syndrome on presentation. Intensive and careful investigation revealed no other origin of the tumor. Resection is the treatment of choice for primary hopatic carcinoid tumors. Their prognosis seems to be more favorable when compared with other hepatic carcinomas

Gastrinoma presentación de un caso y revisión de la literatura / Gastrinome presentation of a case and review of the literature

El gastrinoma es un tumor predominantemente maligno pancreático o extrapancreático (duodeno, yeyuno, proximal, estómago), el cual causa una hipergastrinemia, no regulada y el síndrome de Zollinger-Ellison. Se presenta un caso de un Paciente masculino de 58 años de edad, con antecedentes de gastritis erosiva diagnósticada un año previo a su ingreso, es hospitalizado en agosto del 2001 por episodio de Hemorragía Digestiva Superior originada por ulcera gástrica, es controlado mediante tratamiento médico y tres días despues reingresa con cuadro clínico de ulcuspeptico perforado resolviendose quirúrgicamente con estudio anatomopatológico e inmuno-histoquímico posterior a la intervención de gastrinoma gástrico

Sindrome de zollinger-ellison: análisis de tres casos / Zollinger-ellison syndrome: analysis of three case

Los gastrinomas están entre los tumores neuroendocrinos pancreáticos más frecuentes, y el 60 por ciento son malignos. Al momento del diagnóstico el 50 por ciento ya presentan matástasis aunque se trata de lesiones de bajo grado de malignidad, y el 60 por ciento de estas lesiones se originan en lugares extrapancreáticos. Los tres casos que se analizaron demostraron la utilidad de los niveles de gastrina seriados, la ecoendoscopia y la sintigrafía para receptores de somatostatina marcados con Indio 111 en la detección de lesiones metastásicas

A case of gastric variceal bleeding associated with pancreatic endocrine tumor in the pancreas tail / 대한내과학회지

Isolated obstruction of the splenic vein leads to segmental portal hypertension, which is mainly originated from pancreatic disease, such as chronic pancreatitis, pancreatic pseudocyst, pancreatic cancer. The clinical manifestation are devoid of ascites and encephalopathy, but presented with gastric variceal bleeding. We experienced 27-year-old male patient who complained of hematochezia and melena. After work-up with CT and angiography, we performed operation with the impression of pancreatic tumor associated with splenic vein occlusion. It resulted nonfunctioning pancreatic endocrine tumor. Often called islet cell tumor, pancreatic endocrine tumor has various names according to secreted hormones, such as insulinoma, Zollinger-Ellison syndrome and glucagonoma. It was classified as nonfunctioning tumor if there were any evidence of hormone secretion by radioimmunoassay and immunohistochemistry. Surgical excision and adjuvant medical therapy is the mainstay of therapy. We performed tumor resection and splenectomy for control of gastric variceal bleeding due to splenic vein occlusion.

A Case of Multiple Gastric Carcinoids Associated with Chronic Atrophic Gastritis and Hypergastrinemia / 대한소화기내시경학회지

Gastric carcinoid tumors are so rare that they constitute less than 1% of total primary gastric tumors. They are classified into 3 types: (1) gastric carcionoid associated with chronic atrophic gastritis (type I), (2) gastric carcinoids associated with Zollinger-Ellison syndrome (ZES) or multiple endocrine neoplasm (MEN) type 1 (type II), and (3) sporadic gastric carcinoid (type III). A 55-year-old man underwent a medical check-up. Five polypoid masses were incidentally detected in the cardia, fundus and midbody whose size ranged from 0.5 cm to 1.6 cm in diameter. Tumor cells were strongly positive for cytokeratin, synaptophysin and chromogranin staining. Biopsies from the body and fundus showed severe atrophy. Fasting serum gastrin level was highly increased, 1,098 pg/mL. There was, however, no evidence of the presence of ZES or MEN type 1. The patient underwent total gastrectomy for complete resection and has remained free of any complications with normal serum gastrin level.

Diarreas neuroendocrinas / Neuroendocrine diarrheas

Los cuadros endocrinos son poco frecuentes pero en ellos un porcentaje importante de casos presenta diarrea. Estas diarreas son crónicas; hipersecretoras y abundantes (volúmenes diarios de heces mayores de 500 ml) y en su mayoría son debidas a neoplasias funcionales benignas o malignas, que estimulan la secreción de agua y electrólitos en las criptas de Liberkuhn y también la motilidad intestinal

A Case of Gastritis Cystica Profunda Suspiciously Caused by Gastric Foreign Body / 대한소화기내시경학회지

Gasritis cystica profunda (GCP) is a rare disease in which hyperplasia of mature glandular epithelium extends into the tissues beneath the submucosa. It shows multiple small cysts in the mucosa and submucosa of the stomach. It was firstly reported by Littler and Gleibermann on 1972. GCP is mainly observed at the site of gastroenterostomy but, it may occur in the stomach without a previous history of surgery. The proposed pathogenesis of the these abnormalities are related to ischemia, chronic inflammation and the presence of a foreign body. GCP may present not only as a submucosal tumor or as solitary or diffuse polyps but also as a giant gastric mucosal fold rarely. It should be differentiated from Menetrier's disease, Zollinger-Ellison syndrome, inflammatory disease and malignancy. We present a case of gastritis cystica profunda without having had any previous surgery, suspiciously caused by gastric foreign body. We made a diagnosis based on findings from the esophagogastroduodenoscopy, endoscopic ultrasonography and histologic findings after surgery.