Diarrea crónica como manifestación de un tumor neuroendocrino / Chronic diarrhea as a manifestation of a neuroendocrine tumor

Resumen Las neoplasias neuroendocrinas (Neuroendocrine Neoplasms, NEN) constituyen un grupo heterogéneo de neoplasias poco frecuentes, que se originan en las células endocrinas, con la capacidad de secretar aminas y polipéptidos hormonales. Las NEN de localización pancreática (pNEN) pueden ser funcionales o no funcionales. Las pNEN funcionales secretan hormonas como la gastrina, la insulina y el glucagón y otras menos frecuentes como el péptido intestinal vasoactivo (PIV), por lo que sus características sindromáticas dependen del péptido secretado. Los vipomas se manifiestan con diarrea crónica de características secretoras, que usualmente conducen a trastornos hidroelectrolíticos e incluso a complicaciones serias asociadas como la falla renal. A continuación, se describe el caso de un hombre de 37 años con diarrea crónica de 6 meses de evolución y frecuentes hospitalizaciones por trastornos hidroelectrolíticos, generados por hipocalemia severa y lesión renal aguda por deshidratación. Después de múltiples estudios, se considera el diagnóstico de una diarrea secretora por NEN funcional, secretora de PIV. Por tanto, se inicia una terapia empírica con octreotida y se logra controlar la diarrea, así como corregir el trastorno hidroelectrolítico. Además, se amplían los estudios, para documentar las pNEN tratadas mediante intervención quirúrgica, con respuesta clínica favorable y remisión completa de la sintomatología.

Abstract Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms that originate in endocrine cells with the ability to secrete amines and hormonal polypeptides. Pancreatic neuroendocrine tumors (PNETs) can be functional or non-functional. Functional PNETs secrete common hormones such as gastrin, insulin and glucagon and much less frequent hormones such as vasoactive intestinal peptide (VIP). Their characteristics depend on the peptide secreted. Vipomas are characterized by chronic diarrhea of ​​secretory characteristics that usually lead to hydroelectrolytic disorders and can lead to serious complications associated with renal failure. This article describes the case of a 37-year-old man who had suffered chronic diarrhea with frequent hospitalization for hydroelectrolytic disorders for six months due to severe hypokalemia and acute renal damage due to dehydration. After multiple studies, a diagnosis of secretory diarrhea due to a VIP secretory functional NET was considered. Empirical therapy with Octreotide was begun to control diarrhea and correct the hydroelectrolytic disorder. More studies of PNETS are being published. They have been treated surgically intervention with favorable clinical results and complete remission of symptoms.

VIPoma pancreático tratado com pancreatectomia distal e preservação esplênica com ligadura da artéria esplênica / Pancreatic VIPoma treated with distal pancreatectomy and splenic preservation with ligature of splenic artery

O VIPoma é um tumor neuroendócrino de baixa malignidade derivado das células das ilhotas não-beta do pâncreas, apresenta incidência de 1:10.000.000 pessoas na população e sua localização mais comum é no corpo e cauda do pâncreas. Seu tratamento curativo é cirúrgico, sendo geralmente realizada a pancreatectomia distal com esplenectomia. O caso relatado foi o de uma paciente do sexo feminino, de 31 anos, diagnosticada com VIPoma pancreático. O tratamento realizado foi a pancreatectomia distal com preservação esplênica e ligadura da artéria esplênica. A preservação esplênica diminui a morbidade perioperatória, sem prejudicar o resultado oncológico nos tumores de baixo grau de malignidade.

VIPoma is a low grade malignancy neuroendocrine tumor derived from non-beta pancreatic islet cells, it has an incidence of 1:10.000.000 individuals in the general population and its commoner location is in the body and tail of the pancreas. The curative treatment is surgery, and distal pancreatectomy with splenectomy is usually the employed technique. The case reported was of a female patient, 31 years-old, diagnosed with pancreatic VIPoma. The chosen treatment was distal pancreatectomy with splenic preservation and ligature of the splenic artery. Splenic preservation reduces the perioperatory morbidity, with no prejudice to the oncologic effect in the low grade malignancy tumors.

VIPoma en retroperitoneo de adulto mayor, causa de diarrea crónica en localización infrecuente / VIPoma in retroperitoneum of elderly, cause of chronic diarrhea in uncommon location

La diarrea crónica secretora es una entidad frecuente. Las causas son múltiples, por lo que llegar al diagnóstico definitivo puede resultar demorado con las complicaciones que esto ocasiona en el estado general del paciente. Se presenta el caso de un adulto mayor que cursa con diarrea crónica asociada a hipokalemia leve y acidosis metabolica hiperclorémica secundaria a un VIPoma a nivel de retroperitoneo, la cual es una localización inusual de este tipo de tumores, que en este caso fue diagnosticado mediante una biopsia guiada por tomografía...

Chronic secretory diarrhea is a frequent entity. Causes are multiple, that is why reaching final diagnosis can result in delay with complications that this causes in the general condition of the patient. We present the case of one older adult with chronic diarrhea, mild hypokalemia and metabolic hyperchloremic acidosis secondary to a VIPoma in retroperitoneum which is an unusual location of this type of tumor that was diagnosed by biopsy guided by tomography...

Reporte de segundo caso en Cuba de clorhidrorrea congénita / Report of a second congenital chloride diarrhea case in Cuba

La clorhidrorrea congénita es un raro desorden autosómico recesivo, causado por un defecto en el intercambio de cloruro/bicarbonato en el íleon y colon. En este trabajo se reporta el caso de un niño de 1 año de edad con características patognomónicas de esta condición, consistentes en antecedentes prenatales de polihidramnios, diarreas acuosas desde el nacimiento, poca ganancia de peso, alcalosis metabólica y deshidratación. El diagnóstico fue confirmado por el elevado contenido de cloruro en heces, y es el segundo caso reportado en la literatura cubana.

Congenital chloride diarrhea is a rare autosomal recessive disorder caused by a defective exchange of chloride and bicarbonate in the ileum and the colon. This article reported the case of one-year old child with pathognomonic characteristics of this disease including prenatal history of polyhydramnios, watery diarrheas since birth, low weight gain, metabolic alkalosis and dehydration. The diagnosis was confirmed on the basis of the high contents of chloride in stools. He is the second case of this disease reported in the Cuban literature.

Diagnosis and surgical treatment for pancreatic vasoactive intestine polypeptide tumor / 中南大学学报(医学版)

OBJECTIVE@#To explore the diagnosis and surgical treatment for pancreatic vasoactive intestine polypeptide tumor (VIPoma).@*METHODS@#Clinical data of 7 patients with VIPoma from Xiangya Hospital, Central South University between January 1990 and July 2011 were collected and analyzed retrospectively.@*RESULTS@#The different operation modes were selected according to the location of VIPomas, and the postoperative symptoms of all 7 patients were gradually relieved and cured. The follow up showed that life spans of the above-mentioned patients were 3-6 years.@*CONCLUSION@#The incidence of pancreatic VIPoma is low but it is easy to misdiagnose. The excision for the tumor is the most effective therapy. Combining with somatostatin, intervention and other effective strategies, the life quality of patients can be improved and long-term survival may be achieved.

Significant Symptom Relief with Hepatic Artery Embolization in a VIPoma with Liver Metastases / 대한내과학회지

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) cause VIPoma syndrome, which is characterized by watery diarrhea, hypokalemia, and achlorhydria. The treatment options for metastatic VIPomas include somatostatin analogs, cytoreductive surgery, and chemotherapy. We report the case of a 54-year-old male who presented with a peripancreatic mass with multiple hepatic metastases on computed tomography. After resection, the peripancreatic mass was demonstrated pathologically to be a neuroendocrine tumor. Although the patient received systemic chemotherapy and somatostatin analogs for the hepatic metastatic masses, the tumor increased in size. The patient then experienced severe diarrhea, despite treatment with the somatostatin analogs. Elevated serum VIP levels (3,260 pg/mL) and typical symptoms confirmed the diagnosis of VIPoma. We performed hepatic artery embolization (HAE) to reduce the tumor volume and control his symptoms, which led to a very rapid symptomatic response. The patient has remained symptom-free for 18 months with repeated HAE.

Síndrome diarreico por rotavirus en niños menores de 5 años inmunizados y no de la ciudad de Maracaibo, estado Zulia, Venezuela / Diarrheic syndrome due to rotavirus in immunized and non-immunized children under 5, in the city of Maracaibo, state of Zulia, Venezuela

La diarrea aguda es la causa más común de morbi-mortalidad infantil, donde el Rotavirus es uno de los principales agentes involucrados en las diarreas severas en niños menores de 5 años. El presente estudio tiene como objetivo determinar la presencia de rotavirus en una población infantil con cuadros diarreicos, vacunados y no vacunados que acuden a observación pediátrica del Hospital de Niños y Hospital Universitario de Maracaibo, estado Zulia en el período de Abril 2011 hasta Abril 2012, para ello se recolectaron 100 muestras de heces y para el diagnóstico se utilizó la técnica de Aglutinación Directa en partículas de Látex. Resultaron positivos un 43,6% (24/55) de niños no vacunados y 33,3% (10/30) de niños vacunados afectando principalmente a los menores de 1 año con predominio del sexo masculino con un 65,9% sobre el sexo femenino con 40%, la diarrea por el agente viral estudiado representó casi la mitad de las hospitalizaciones por gastroenteritis, encontrándose una diferencia estadística significativa de p= 0.027 en el numero de evacuaciones del cuarto día, entre niños no vacunados (5) y vacunados (3). Los resultados de esta investigación muestran la circulación de rotavirus en niños vacunados y no vacunados, es por ello importante considerar que el presente reporte tiene como fin último alertar a la comunidad médica a considerar en todo niño con gastroenteritis la posibilidad de que se trate de un cuadro por RV.

Acute diarrhea is the most common cause of morbidity and mortality in infants, where rotavirus is one of the main agents involved in severe diarrhea for children under five years. The present study aims to determine the presence of rotavirus in a vaccinated and unvaccinated pediatric population with acute diarrhea that came to the Children’s Hospital and the University Hospital of Maracaibo, State of Zulia, for observation from April 2011 to April 2012. One-hundred stool samples were collected and direct agglutination of latex particles was used for diagnosis. 43.6% of the unvaccinated children were positive (24/55) as were 33.3% (10/30) of the vaccinated children. Principally, children under 1 year were affected, predominantly males with 65.9% and females with 40%. Diarrhea due to the viral agent under study accounted for nearly half the hospitalizations for gastroenteritis. A statistically significant difference of p = 0.027 was found between the number of evacuations on the fourth day in unvaccinated (5) and vaccinated (3) children. Results of this research show rotavirus circulating in vaccinated and unvaccinated children. Therefore, the purpose of this report is to alert the medical community to consider that every child with gastroenteritis could possibly have RV.

Pancreatic neuroendocrine tumors: biology, diagnosis,and treatment / 癌症

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.

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.

VIPoma Crisis: Immediate and life saving reduction of massive stool volumes on starting treatment with octreotide

We report the case of a 57-year-old male physician who presented with a life threatening secretory and refractory diarrhoea of around 20 L/day. This was complicated by severe hypotension, hypokalaemia, hypercalcaemia, renal failure requiring dialysis, metabolic acidosis, cardiorespiratory arrest and ventilation for 12 days. His diarrhoea responded immediately to the first dose of a therapeutic trial of subcutaneous octreotide 100 mcg 8 hourly which was started on clinical grounds alone before any investigations were carried out. After one day he was extubated and his blood pressure returned to normal. When a functioning neuroendocrine tumour is suspected clinically, the use of octreotide can, as in this case, be life saving

VIPoma pancreático: Caso clínico / Pancreatic VIPoma: Report of one case

Neuroendocrine tumors are uncommon, including VIPoma that produces vasoactive intestinal polypeptide. We report a 45-year-old female presenting with a history of diarrhea lasting three months. An abdominal CAT scan showed a solid tumor in the body of the pancreas. A fine needle aspiration biopsy of the tumor was compatible with a neuroendocrine tumor. The patient was subjected to a partial pancreatectomy, excising a 4 cm diameter tumor. The pathological study was compatible with a neuroendocrine carcinoma. There was no regional lymph node involvement. During the postoperative period the results of serum vasoactive intestinal polypeptide were received. These were 815.9 pg/ml before surgery and normalized after the operation.

Prevalence of cholera in pediatric patients with acute dehydrating diarrhea.

Objective. To estimate the prevalence of culture-confirmed cholera in patients with acute dehydrating diarrhea, at a tertiary care center in north India, during a 6-month period from March to August, 2006. Methods. We studied 145 children, who presented to the pediatric emergency services of a tertiary care teaching hospital in north India with acute dehydrating diarrhea. Each patient had his/her stool sample collected for Vibrio cholerae culture and hanging drop preparation for darting motility. The stool specimen for hanging drop analysis was immediately transported to the emergency laboratory, where a trained technician prepared the slides and examined them for darting motility characteristic of Vibrio cholerae. Results. V. cholerae was isolated in 36 (24.8%) patients. Forty-nine (33.7%) patients had a positive hanging drop examination. Hanging drop examination had a sensitivity and specificity of 85.8% and 81.7%, respectively. Severe dehydration (OR 4.3; P<0.01) and hanging drop positivity (OR 12.42; P<0.001) were associated with higher odds of cholera after adjustment for other risk factors. Conclusion. Cholera is an important cause of acute watery diarrhea in pediatric patients in urban north India and should be ruled out in all children presenting with acute dehydrating diarrhea, particularly those with severe dehydration. Hanging drop test is useful for diagnosis in the emergency setting.

Diarrea crónica como manifestación de tumor neuroendocrino metastásico / Chronic diarrhea as presenting symptom for a metastasic neuroendocrine tumor

Se presenta el caso de una paciente femenina de 74 años de edad, con cuadro de diarrea acuosa severa, hipocalemia importante y metástasis hepáticas, documentándose en su autopsia un tumor neuroendocrino primario en el páncreas como causa de su cuadro. Se presenta una revisión de la literatura sobre los tumores neuroendocrinos del páncreas con énfasis en el VIPoma, por su correspondencia con el caso de esta paciente.

A Case of Multiple Endocrine Neoplasia Associated with VIPoma / 대한내분비학회지

Multiple endocrine neoplasia I(MEN I) is a genetic disorder that consists of neoplasia of neuroendocrine type in the parathyroid glands, in the islets of Langerhans in the pancreas, and in the anterior pituitary gland. Primary hyperparathyroidism is the most common feature and occurs in approximately 95% of MEN I patients. Pancreatic islet cell tumors occur in 40% of MEN I patients. Most of these tumors produce excessive amounts of hormones, such as gastrin, insulin, glucagon and vasoactive intestinal polypeptide(VIP). VIP-producing pancreatic tumors(VIPoma) associated with MEN I are rare and so far only one has been reported in Korea. Recently, we came across a case of MEN I, associated VIPoma presented persistent hypercalcemia after a parathyroidectomy. A 70 year old man had suffered from large amount of watery diarrhea, severe general weakness and paralysis of lower limbs for 3 months which suggests symptoms of hypercalcemia. Before the patient visited our hospital, he underwent subtotal parathyroidectomy due to hyperparathyroidism. Even though he was operation, there was no subsidization of the symptoms and abnormal findings of blood chemistry such as hypercalcemia, hypocalemia were remained unchanged. However, the parathyroid hormone level was still within normal limits. Abdominal computerized tomography scan demonstrated a mass of 2.5cm diameter in tail of the pancreas. As serum level of VIP hormone was also elevated, distal pancreatectomy was carried out to performed. There was improvement in the symptoms towards the normal condition and the level of biochemical parameters such as serum potassium, calcium and VIP, were also within the normal limits. In a direct sequence analysis, GAC-->CAT(Asp-->His) point mutation, at codon 383 of exon 9 of the MEN I gene was identified in both the patient and his son. The authors report a rare case of VIPoma associated with MEN I with review of literature on MEN I.

Mulher branca, 45 anos, consulta por diarréia crônica, emagrecimento e anemia ferropênica / 45-year-old, white woman presents with chronic diarrhea, weight loss and iron deficiency anemia

Em novembro de 1996, uma mulher branca de 45 anos veio à consulta por diarréia aquosa e emagrecimento acentuado. Negava tabagismo e alcoolismo. Ao exame físico, apresentava mucosas hipocoradas e emagrecimento. Trazia consigo o laudo de uma endoscopia digestiva alta considerada normal e de uma colonoscopia com descrição de cólon espástico. Os exames mostraram, no soro: glicose, 74 mg/dL; uréia, 13 mg/dL; creatinina, 0,4 mg/dL; sódio, 137 mEq/L; e potássio, 4,3 mEq/L. A pesquisa de leucócitos fecais e o parasitológico de fezes foram negativos (três amostras). Foi iniciado sulfato ferroso via oral. A reavaliação, em fevereiro de 1997, mostrou os exames contidos na tabela 1, além de: alanina aminotransferase (ALT), 57 UI/L (3-17); aspartato aminotransferase (AST), 62 UI/L (9-36); bilirrubinas e provas de coagulação normais. Foi iniciada a suplementação de ácido fólico. Como havia queixa de menorragia, a paciente foi avaliada por ginecologista, que indicou reposição hormonal. Em abril de 1998, a paciente persistia com queixa de menorragia e emagrecimento. Foi submetida a nova endoscopia digestiva alta, que evidenciou algumas erosões com fibrina, no antro, e mucosa de bulbo duodenal com aspecto ladrilhado

Diagnosis and treatment of vasoactive intestinal peptide-secreting-tumors: one case report and 15 years review in China / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the experiences of diagnosis and treatment for vasoactive intestinal peptide-secreting-tumors (VIPoma) by summarizing clinical informations of 15 patients with VIPoma.</p><p><b>METHODS</b>To analyze Clinical manifestations, laboratory examinations, imaging features, operation, pathological findings and follow up survey of 15 patients, among them 1 case from our hospital and the other 14 cases were searched in chinese biological and medical literature database from Jan 1987 to Dec 2002.</p><p><b>RESULTS</b>The main clinical manifestation include periodical secretory watery diarrhea, hypokalemia, achlorhydria, in addition, periodical backache, skin rash, and polyps of colon were presented in the case in our hospital. The immunohistochemical expression of many kinds of digestive hormone including VIP presented positive; All clinical symptoms of which except polyps disappeared after operation, elevated VIP data in serum also markedly decreased. Part resection of superior mesenteric vein was performed in the same patient.</p><p><b>CONCLUSIONS</b>VIPoma is rare. Typical symptoms and the serum value of VIP were keys to diagnosis, the operation is the most effective means for treatment. Resection of tumor, Radiofrequency tissue ablation, liver transplantation can be selected for metastatic VIPoma in the liver.</p>

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