Immunohistochemical expression of somatostatin receptors in digestive endocrine tumours.

INTRODUCTION: Somatostatin receptors are expressed in a large number of human tumours. The somatostatin receptors types 1-5 expression in a series including 100 gastro-entero-pancreatic endocrine tumours were analysed. METHODS: From a prospectively built database of patients with gastro-entero-pancreatic endocrine tumours referred from three institutions, 100 cases with clinical and pathological data were selected. Somatostatin receptors expression by immunohistochemistry with somatostatin receptor types 1-5 antibodies in tissue paraffin sections were studied and correlated with the histological diagnosis according to the WHO classification, location and functional status. RESULTS: Of the 100 cases, 67 were gastrointestinal tumours, 25 pancreatic and 8 liver metastasis of unknown origin. Thirty-one of them were functioning tumours: 2 insulinomas, 5 gastrinomas, 1 glucagonoma and 23 carcinoids. Somatostatin receptors expression was observed in 94 tumours. The six negative cases were all non-functioning tumours. Somatostatin receptors 2a and 5 were highly expressed (86 and 62%, respectively), and surprisingly found even in poorly differentiated endocrine carcinomas. Somatostatin receptors expression was less frequent in pancreatic than in gastrointestinal tumours. Well-differentiated neoplasms had a higher density of somatostatin receptors. Only SSTR2a showed membrane staining. CONCLUSIONS: Immunohistochemistry revealed that somatostatin receptors were highly expressed in both primary and metastatic gastro-entero-pancreatic endocrine tumours with heterogeneous staining distribution. It proved to be a reliable technique even in small tumour samples.

Management of neuroendocrine tumors: a meeting of experts from Latin America.

A panel of experts from Latin America convened in Brazil, in May of 2007, for consensus recommendations regarding the management of neuroendocrine tumors (NETs) of the gastrointestinal tract and pancreas. The recently introduced World Health Organization classification of NETs represents a step forward, but the former classification of carcinoids into foregut, midgut and hindgut is still likely to be useful in the near future. Macroscopic description of the tumor should be followed by light microscopic examination and immunohistochemical staining, whereas other techniques might not be widely available in Latin America. Surgery remains the mainstay of treatment for patients with potentially curable tumors, and adequate selection is paramount in order to optimize treatment results. Regarding systemic therapy, patients with well-differentiated tumors or islet-cell carcinomas may be categorized as having indolent disease, while patients with poorly differentiated, anaplastic, and small-cell carcinomas, or with atypical carcinoids, may be approached initially as having aggressive disease. Somatostatin analogues play a cytostatic role in indolent tumors, and chemotherapy may play a role against other, more aggressive NETs. Obviously, there is an urgent need for novel therapies that are effective against NETs.

Penetrance and clinical manifestations of non-hotspot germline RET mutation, C630R, in a family with medullary thyroid carcinoma.

Germline mutations in specific hot spot-codons of the RET proto-oncogene are associated with multiple endocrine neoplasia type 2 (MEN 2). Clinical RET gene testing has been routine for the last 10 years in some countries. In Argentina, RET testing excluding MEN 2B was always reported with a mutation at codon 634, with one exception: we described a novel mutation T > C transition at codon 630 (C630R), the family to which we extend the study in the present report. This family comprised 29 members in four generations including 6 individuals affected with medullary thyroid cancer (MTC), positive for the C630R mutation and normal adrenaline/ noradrenaline and ionized calcium/parathyroid hormone levels. Two asymptomatic mutation carriers aged 5 and 11 years underwent total thyroidectomy. The histopathologic examination showed C-cell hyperplasia and microcarcinoma foci, while preoperative basal calcitonins were normal for both. Our report emphasizes the importance of testing for non-hot spot RET mutations in apparently mutation negative MEN 2 families. Furthermore, it would appear that C630R mirrors C634R in penetrance (100% in this family) and in early age of onset of MTC, although paradoxically, no pheochromocytomas and hyperparathyroidism have developed. In addition to recommending RET testing before 5 years of age; we also can postulate that codon 630 may be the key point along the extracellular domain, important in the tissue-specific penetrance.

G-cells and gastrinaemia in chronic nonspecific bulbitis.

Chronic nonspecific bulbitis (CNB), the number of G-cells in the antrum and the level of serum gastrin were unrelated in a group of 24 patients. Gastrin may be produced by cells outside the antrum or by a few but hyperactive antral G-cells.

Abdomen agudo como forma de presentación de un adenoma hepático

Reportamos el caso de una mujer de 33 años que fue internada con un cuadro de abdomen agudo. Refería ingesta de anticonceptivos orales. Los hallazgos físicos fueron dolor abdominal, defensa y rigidez del cuadrante superior derecho. Se realizaron los seguientes estudios: los tests de laboratorio excluyeron hidatidosis y amebiasis. La ecografía mostró una imagen nodular en el lóbulo hepático derecho y una vía biliar normal. Con la tomográfia computada se observó una masa de baja densidad. Una biopsia con aguja guiada tomográficamente fue informada como hepatocitos normales. La angiografía mostró arterias hepáticas tortuosas. La laparoscopía reveló una formación sólida y se obtuvo sangre al punzarla. Se indicó una laparotimía. Se encontró un tumor en el lóbulo hepático derecho pero el cirujano no resecó la lelsión porque una biopsia por congelación no consiguió demostrar células tumorales. Se llegó l diagnóstico de adenoma hepático con la biopsia definitiva. Nuestra paciente tuvo buena evolución con la suspensión de los anticonceptivos y una tomografía demostró la remisión casi completa del tumor un año después de la cirugía. En 12-52% de los pacientes con un adenoma hepático se observó dolor como el síntoma inicial y comienzo brusco em 33% de ellos. Sin embargo no se considera frecuentemente este tumor como causa de abdomen agudo

[Acute abdomen as form of presentation of hepatic adenoma]. / Abdomen agudo como forma de presentación de un adenoma hepático.

We report the case of a woman aged 33 years old who was admitted with an acute abdomen. She referred oral contraceptives intake. Physical findings were abdominal tenderness, involuntary guarding and right upper quadrant rigidity. The following studies were performed: laboratory tests excluded hydatidosis and amebiasis. Ultrasonography showed a nodular image in the right hepatic lobe and a normal biliary tract. A low-density mass was observed with the computed tomographic scanning. A tomographic guided needle biopsy was informed as normal liver cells. Angiography showed tortuous hepatic arteries. Laparoscopy revealed a solid formation blood was obtained when it was punctured. Laparotomy was indicated. A tumor in the right hepatic lobe was found but a surgeon did not resect the lesion because a congelation biopsy failed to demonstrate tumoral cells. The diagnosis of hepatic adenoma was reached with the definitive biopsy. Our patient had a good evolution with the contraceptives withdrawal and a tomographic scanning one year after surgery showed the almost complete remission of the tumor. Pain as the initial symptom was observed in 12-52% of patients with an hepatic adenoma an audden onset in 33% of them. However this tumor is not frequently considered as a cause of acute abdomen.

PIP: The case is described of a 33-year-old woman with an 8-year history of oral contraceptive (OC) use who was treated at a hospital in Buenos Aires for a hepatic adenoma. The woman was admitted with an acute abdomen. Apart from OC use she had a history of hypertension for which she was treated with clonidine and diuretics. The physical findings included pain in the right abdomen, involuntary guarding, vomiting, and fever. Ultrasonography showed a normal bladder and pancreas and a nodular image in the right hepatic lobe. A CAT scan revealed a mass in the right hepatic lobe, and a needle biopsy later showed normal hepatic cells. Laparoscopy revealed a solid formation from which blood was obtained on puncturing. Angiography showed tortuous hepatic arteries. Laboratory tests were normal. An exploratory laparotomy was performed when the different studies failed to establish a clear diagnosis. A tumor was found in the right hepatic lobe but was not respected because the frozen section biopsy did not show malignant cells. The definite diagnosis of hepatic adenoma was based on the definitive biopsy. OC treatment was terminated and the tumor was in almost complete remission 1 year later. Hepatic adenomas are benign tumors, usually single, which occur rarely and primarily in women aged 30-40 who use OCs. A review of the literature indicated that the forms of presentation of hepatic adenoma are very varied. Pain was the initial symptom in 12-52% of cases. The pain was of sudden onset in 1/3. Hepatic adenoma is however infrequently considered as a cause of acute abdomen. Treatment in 73% of cases is surgical because of the danger of hemorrhage and shock and because of the potential for malignant transformation.

Biopsia peroral por succión del intestino delgado dirigida bajo control endoscópico / Peroral suction biopsy of the small intestine directed under endoscopic control

Con el objeto de evaluar el procedimiento de biopsia-succión de la mucosa del intestino delgado dirigida bajo control endoscópico, fueron estudiados 47 pacientes. Sobre un total de 121 muestras obtenidos resultaron adecuadas para diagnóstico 114 muestras (94,2%). Este procedimiento resultó ser efectivo, rápido y seguro para el estudio de la patología de la mucosa yeyunal

[Peroral suction biopsy of the small intestine directed under endoscopic monitoring]. / Biopsia peroral por succión del intestino delgado dirigida bajo control endoscópico.

The technical difficulties of the procedures for jejunal biopsy are a waste of time. In the present paper we consider the suction biopsy of small bowel with the Olympus equipment, under endoscopic control. We studied 47 patients, mean age 46 years old (range 22-70) with clinical suggestion of malabsorption. In all patients, we tried to obtain 3 samples, in 31 (66%) we obtained the 3, in 8 (17%) we obtained 2 and in 2 (4.2%) no samples. With this procedure we had 121 samples; from these 114 (94.2%) were useful for diagnosis. We had no complications. The small bowel biopsy with Olympus system was fast, sure and effective.

Cardiotoxicidad de la adriamicina: estudio farmacológico e histopatológico en ratas / Cardiotoxicity of adriamycin: pharmacological and histopathological study in rats

Trabajos recientes mostraron una disminución en la respuesta adrenérgica miocárdica en la insuficiencia cardíaca. Por ello evaluamos los efectos de un tratamiento subagudo con ADM sobre la actividad cardíaca de noradrenalina (NA) e ISOproterenol (ISO). Ratas Wistar de ambos sexos (300-400 g) recibieron ADM 4 mg/kg i.v. en los días 1 y 8. Los controles fueron inyectados con solución fisiológica. El día 21 se sacrificaron los animales y se estudió la histopatología cardíaca. Mediante curvas concentración-respuesta, se evaluó la actividad cronotrópica (CRONO) de NA en la aurícula dreecha aislada (Krebs-carbogeno, 37 grados centígrados). El efecto inotrópico (INO) de NA e ISO fue estudiado en aurícula izquierda, estimulada a 3 Hz. Cada grupo experimental incluyó 4-6 ratas. Las curvas concentración-respuesta a NA revelaron: 1) Desplazamiento a la derecha para CRONO en el grupo ADM (ED 50:7,1 + ou - 1,7. 10-7M versus 3,0 + ou - 1,4.10-8 M en controles; p<0,01).2) Un fenómeno similar para INO (ED 50:2,8 + ou - 0,2.10-7 M con ADM versus 2,3 + ou - 0,7.10-8 en controles; p<0,01). Con ISO, se obtuvieron resutados similares en INO (ED 50:1,8 + ou - 0,7.10-8 M con ADM, versus 3,6 + ou - 1,7.10-10 M en controles; p<0,001). Las ratas tratadas con ADM presentaron ascitis, derrame pleural y lesiones miocárdicas (miocitolisis, vacuolización, infiltración linfocitaria), no así las ratas control. El tratamiento subagudo con ADM deprime la respuesta beta-adrenérgica miocárdica en ratas. Este fenómeno se acompaña de signos histopatológicos de daño cardíaco. El presente modelo puede ser útil para evaluar posibles agentes protectores de la cardiotoxicidad promovida por la ADM

Immunohistochemical findings in acute atherosis associated with intrauterine growth retardation.

Lesions of acute atherosis in 23 placentas from pregnancies complicated by fetal growth retardation (less than tenth percentile) were studied by an immunoperoxidase staining. Twelve of them were from normotensive pregnancies, ten complicated by pregnancy induced hypertension, and the remaining associated with systemic lupus erythematosus. Twenty-three placentas with physiological changes of the spiral arteries corresponding to normal pregnancies served as controls. Six of the cases complicated by fetal growth retardation showed absence of physiological changes in basal decidua. Massive intramural granular deposits of IgM, a smaller amount of C3 and C1q, and slight deposits of IgA and IgG were found in vessels with acute atherosis. No intramural deposition of immunoglobulins or complement was observed in vessels with or without physiological changes. The presence of granular deposits of immunoglobulins and complement within the vessel walls with acute atherosis may be related to an immunological disorder, probably mediated by immune complexes.

Response to acute hCG stimulation and steroidogenic potential of Leydig cell fibroblastic precursors in humans.

The process of early testosterone (T) secretion and Leydig cell differentiation in humans was studied to explore the steroidogenic capacity of Leydig cell fibroblastic precursors. Seven cryptorchid boys received hCG prior to orchidopexy. Patients CP, PB, and MR received one injection of 1000 IU; patients JR and GG, three daily injections of 1000 IU, and patients MP and MM, five daily injections of 1000 IU. A testicular biopsy was obtained at the time of operation, 24 hours after the last injection. Serum T (ng/dl) before and after hCG stimulation and testicular T (ng/g) were determined by RIA. A control prepubertal testis (tumoral orchidectomy) was incubated in vitro and showed a time-dependent accumulation of T both in the medium and the testicular tissue. Testosterone released into the medium at 1, 2, and 4 hours was 0.76, 1.43, and 4.03 ng/ml, respectively. Tissue T at 0, 1, 2, and 4 hours was 9, 11, 16, and 24 ng/g, respectively. This indicates synthesis and secretion of T into the medium. Control testes showed abundant fibroblastic precursors with scanty cytoplasm, few organelles, heterochromatic nuclei, and minute nucleoli. No Leydig cells were present. After 1 day of hCG stimulation, numerous fibroblasts were activated, displaying enlarged cytoplasms with increased numbers of organelles, nuclei rich in euchromatin, and bigger nucleoli. No Leydig cells were present. Basal serum testosterone was 58.2 +/- 45.3 ng/dl and 87.3 +/- 42.0 after hCG administration, while testicular T was 974.0 +/- 686.0 ng/g (control prepubertal testicular T is 10-50 ng/g). After 3 days of hCG, activated fibroblasts increased and immature Leydig cells appeared. Basal serum T was 35.5 +/- 7.8 ng/dl and 394.0 +/- 24.0 after hCG stimulation, while testicular T rose to 2797.5 +/- 1222.6 ng/g. After 5 days, mature Leydig cells appeared for the first time. Serum T was 58 +/- 59.3 ng/dl (basal) and 641.5 +/- 390 ng/dl (after hCG); testicular T was 789 ng/g (patient MM did not have a value for testicular T). HCG induced numerous coated pits and endocytic vesicles in activated fibroblasts and young Leydig cells, suggesting receptor aggregation and internalization of hormone-receptor complexes. Peroxidase-antiperoxidase (PAP) localization of T was positive in peritubular fibroblasts and Leydig cells.(ABSTRACT TRUNCATED AT 400 WORDS)

[Evaluation of Ig and muramidase (lysozyme) in unspecified chronic duodenitis (bulbitis)]. / Valoración de Ig y muramidasa (lisozima) en la duodenitis crónica inespecífica (bulbitis).

In 158 patients with symptoms of non ulcerative dyspepsia, endoscopic, histologic and immunohystochemical studies were performed over three years with the aim of investigating the immunological involvement in the Chronic non specific Duodenitis (CND). After excluding 112 patients with associated pathologies of those not fulfilling technics requisites, a population of 46 subjects was selected and subsequently it was subdivided into four groups. A group of 15 patients with histologically normal duodeno served as control; the rest (31 patients) were grouped according to duodenal compromise into three groups of minor-major severity; Grade 1 (n=12); Grade 2 (n=12); Grade 3 (n=7). The number of immunoglobuline producing cells by mn2 of mucosal area and semiquantitative evaluation of mononucleated cells with cytoplasmatic activity to hydrolitic enzymes (lysozyme or muramidase) were compared among the 4 sub-groups. It was observed a variation in the immunoglobulines rate among controls (IgA: M: G=82, 52: 11, 01: 6,45) regarding the most severe degree (61, 56: 27,30: 11,14). The increase of IgMy G compared with controls was highly significant (p is less than 0.001) and it was noted a correlative IgA diminution. The contribution of hydrolitic enzymes through the presence of "activated" histiocytes was maximal in the most degree-coinciding with the increase of IgM and IgG. This findings indicated that a marked local activation of the Immunitary System type B is observed in the Chronic Nonspecific Duodenitis and its increment, expressed as quali-quantitative variations of the different immunologlobulines and muramidase producing cells, should have lythic activity in the highest degrees. We conclude, proposing this disease as a model of immunological aggression which affects bulbar mucosae.

[Catarrhal stomatitis of the gastric stump. Histological changes]. / Estomatitis catarral del muñón gástrico. Alteraciones histológicas.

The prospective investigation here presented tries to show the histologic changes produced in the endoscopic mucosal erythema zone of the gastric stump, which is the largest exposition and reactivity site to which the duodenal-biliary reflux damages. 56 clinically asynthomatic patients have been studied through directed biopsy. The observed results are: great prevailing of chronic gastritis and a high percentage of intestinal metaplasia which, in both cases are in close correlation with the age of the patient and not with his surgical age. There is not any relation either with age or intensity in the different degrees of dysplasia. We came to the conclusion that the erythema does not constitute by it self a histologic perfile different from the rest of the remaining gastric stump.

Estomatitis catarral del munon gastrico. Alteraciones histologicas. / Catarrhal stomatitis of the gastric stump. Histological changes

La investigacion prospectiva aqui presentada intenta mostrar los cambios histologicos producidos en la zona de estomitis endoscopica del munon gastrico, que es lugar de mayor exposicion y reactividad a la exposicion del reflujo duodeno-biliar.Se estudian 56 pacientes asintomaticos clinicamente mediante biopsia dirigida.Como resultados se observa una gran prevalencia de gastritis cronica y un alto porcentaje de metaplasia intestinal, que en ambos casos tiene cerrada correlacion con la edad del paciente y no con su edad quirurgica. No se encontro relacion de edad ni intensidad en los diferentes casos de displasia. Se concluye que la estomitis no constituye por si sola un perfil histologico distinto del resto del munon remanente

[Peroxidase immunohistochemical localization of the epidermal growth factor and/or urogastrone: 2 polypeptides present in the digestive tract]. / Localización inmunohistoquímica con peroxidasa del factor de crecimiento epidérmico (EGF) y/o urogastrona (URO): dos polipéptidos presentes en el aparato digestivo.

Cytoplasmic localization of the antigen Epidermal Growth Factor (EGF) in Brunner's gland cells and in ductal submandibulary gland cells of rats has been effected by using the indirect immunoperoxidase antibody technique with an immunoserum obtained from highly purified extract of EGF/Urogastrone. After fixing in a buffered formaldehyde solution, the sections have been imbedded in paraffin. Structural and immunological properties have been well preserved by immunohistochemical specific techniques. These two polypeptides have similar biological activities and may therefore play an important role as therapeutic factors protectings against acid gastric secretion. An extensive revision and analysis of present stage of knowledge on these two substances which are active participants in the process of acid gastric secretion, has also been carried out.