Clinical features, diagnosis and therapy of pituicytoma: an update.

BACKGROUND: Pituicytomas (PTs) are extremely rare, low-grade glial tumors closely related to the neurohypophyseal axis. Definite conclusions concerning the optimal diagnostic and therapeutic approach to these neoplasms are lacking to date, as most of this information has been presented as case reports. METHODS: Retrospective review of case reports published in the scientific literature to date, including a new illustrative example treated in our department. RESULTS: 116 cases were collected. PTs had a higher prevalence in the fifth and sixth decades of life, with a slight male predominance. Main symptoms, which tended to be progressive, included visual field defects and pituitary-hypothalamic dysfunction. Radiologically, PTs were found anywhere along the hypothalamic-pituitary axis mimicking other, more frequent tumors growing in this anatomical region. Surgical treatment included both transcranial or transsphenoidal approaches, and resulted in gross total resection and morbidity rates of 46.8 and 59%, respectively; the latter essentially consisted in anterior and posterior pituitary dysfunction, with limited impact on daily quality of life. CONCLUSIONS: Due to both low frequency and the absence of pathognomonic clinical and/or radiological features, formulating a suspicion diagnosis of PT represents a considerable challenge even for experienced professionals. The indication for treatment should be made on an individual basis, but it is inescapable in the presence of a visual field defect. The surgical approach has to be tailored according to the topography of the tumor and preoperative symptoms; the greatest challenges in accomplishing a gross total removal are represented by the degree of adherence and vascularization of the PT.

Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity.

BACKGROUND AND AIM: Male hypogonadism has been linked to obesity and diabetes. We aimed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients submitted to bariatric surgery. SUBJECTS AND METHODS: Prospective intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss. Serum testosterone, SHBG, fasting glucose, and insulin were measured among others. Free testosterone was calculated with the Vermeulen formula and insulin sensitivity with the homeostatic model assessment (HOMA). RESULTS: At baseline, thirteen patients had low total testosterone levels, whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group. After bariatric surgery total testosterone, SHBG, and free testosterone significantly increased and achieved normal values in all evaluated patients. Insulin sensitivity improved in all of them. Multivariate linear regression showed that changes in fasting glucose (ß=-1.868, p=0.001), insulin (ß=-3.782, p=0.001), weight (ß=-0.622, p=0.002), and SHBG (ß=-0.635, p=0.022) were associated with changes in free testosterone (adjusted R2=0.936, F=26.613, p=0.001). When insulin resistance calculated by HOMA was in the model instead of insulin and glucose, it also was associated (ß=-3.488, p=0.008) with free testosterone (adjusted R2=0.821, F=11.111, p=0.005). CONCLUSIONS: Circulating tes tos terone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity.

Serum concentrations of osteocalcin, procollagen type 1 N-terminal propeptide and beta-CrossLaps in obese subjects with varying degrees of glucose tolerance.

AIMS: To evaluate serum levels of osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1PN) and beta-CrossLaps (beta-CTx) in obese subjects and their relationship with glucose metabolism parameters. SUBJECTS: Sixty-four obese patients classified according to their glucose tolerance. DESIGN: Case-control study. MEASUREMENTS: A 75-g oral glucose tolerance test was performed with determinations of glucose and insulin between 0 and 120 min. Serum concentrations of OC, P1PN and beta-CTx were quantified in baseline samples. RESULTS: Patients with type 2 diabetes (T2D, n = 24) exhibited OC serum levels (2·6 ± 1·0 nm) significantly lower than those found in subjects with normal glucose tolerance (NGT, n = 20, 3·9 ± 1·5 nm, P < 0·01). We found no significant differences in P1NP and beta-CTX levels among patients with NGT, prediabetes and T2D. Multiple regression analysis showed that serum OC concentration, but not P1NP or beta-CTx levels, was independently related to 2-h plasma glucose. CONCLUSION: Obese patients with T2D showed significantly reduced levels of OC in comparison with patients with lower degrees of glucose tolerance derangement. Our results also suggest that OC was the only bone marker independently related to the degree of glucose metabolism derangement in these patients.

A transcriptional signature associated with the onset of benign prostate hyperplasia in a canine model.

BACKGROUND: Benign prostatic hyperplasia (BPH) represents the most frequent proliferative abnormality of the human prostate. In spite of the well-characterized architectural development of BPH, little is known about the cellular and molecular events that contribute to it. METHODS: We have developed an animal model to evaluate the follow-up of hormone-induced BPH and the analysis of the gene expression associated with BPH. Immunohistochemistry on human patient samples validated the BPH-related molecular alterations. RESULTS: Canine specific Affymetrix microarray analysis performed on sequential biopsies obtained from a beagle dog dynamic model characterized a number of genes altered during the onset of BPH. In addition to the genes involved in calcification, matrix remodeling, detoxification, cell movement, and mucosa protection (MGP, MMP2, TIMP2, ITIH3, GST, MT2A, SULT1A1, FKBP1B, MUC1, STRBP, TFF3), the up-regulation of TGFB3 and CLU indicated a complete adjustment of the transdifferentiation, senescence and apoptosis programs. The up-regulation of Clusterin was validated by RT-qPCR and immunohistochemistry, both in the dog dynamic model and in human samples, further confirming the suitability of the animal model for the study of the molecular alterations associated with BPH. CONCLUSIONS: Transcriptome analysis performed on a dynamic animal model that accurately mimicked the human clinic, allowed us to characterize a gene expression pattern associated with the onset of BPH.

Right adrenal metastases of hepatocarcinoma after liver transplantation: case report and literature review.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most common malignancies globally, accounting for nearly one million new cases per year. Although the treatment of extrahepatic metastases from primary liver tumors is essentially palliative, a solitary metastasis from such tumors offers a possibility of cure by surgical resection. The adrenal gland is an uncommon site for metastasis from primary liver tumors. METHODS: We report a liver transplantation case of HCC and hepatitis B virus in a 23-year-old man with an excellent postoperative result. However, because an increased alpha-fetoprotein was evident and complete radiologic and blood tests were performed, all of which were normal. Three years posttransplantation, a right adrenal mass was identified by CT. PAAF was performed as well as adrenalectomy for a solitary adrenal metastasis from hepatocellular carcinoma. RESULTS: The patient underwent adrenalectomy for the right adrenal metastasis at 3 years following liver transplantation for HCC. He is presently alive and disease-free 24 months after adrenalectomy. CONCLUSION: Carefully selected patients with solitary metastasis from HCC may be considered for resection.

Role of calcium malabsorption in the development of secondary hyperparathyroidism after biliopancreatic diversion.

Secondary hyperparathyroidism (SH) is a frequent metabolic complication of bariatric surgery. Around 70%of patients who undergo biliopancreatic diversion (BPD) have this complication in the long term. The aim of this study was to evaluate the relative influence of vitamin D deficiency and calcium malabsorption in the development of SH in patients who underwent BPD. We reviewed the mean values of PTH throughout the post-operative follow-up and of related biochemical data (25-hydroxyvitamin D, calcium, magnesium) of 121 patients who underwent BPD at our institute from November 1996 to November 2004 (mean follow-up 66 months). Mean PTH correlated negatively with mean 25-hydroxyvitamin D (r=-0.27, p=0.003) and with urinary calcium(r=-0.19, p=0.047), and positively with age (r=0.22, p=0.018). However, a high mean PTH was found in 48.7% patients with mean 25-hydroxyvitamin D >or=30 ng/ml and in 80.0% patients with mean 25-hydroxyvitamin D between 20 and 30 ng/ml. The mean PTH was normal in 5 patients without calcium supplements at present, and progressively increased in parallel to the calcium dose in the rest of patients, although mean 25-hydroxyvitamin D levels were not related to the calcium dose. Our data suggest that individual differences in active and/or passive calcium absorption determine intractable SH after BPD in around half of the patients who have normal levels of 25-hydroxyvitamin D and in 80% of patients with 25-hydroxyvitamin D levels between 20 and 30 ng/ml after BPD, worsening with age.

[Importance of artificial nutrition in the resolution and etiologic diagnosis of severe chronic diarrhea: a propos of a case]. / Importancia de la nutrición artificial en la resolución y diagnóstico etiológico de diarrea crónica severa: a propósito de un caso.

We present a case of severe chronic diarrhea requiring parenteral nutritional support to both cover the nutritional needs and allow for intestinal rest for later adaptation to enteral nutrition, altogether allowing for the etiologic diagnosis and disease healing.

Plasma mineral content in type-2 diabetic patients and their association with the metabolic syndrome.

BACKGROUND: Metabolic syndrome is a clinical disorder that is becoming more prevalent in Spain. The syndrome encompasses a set of metabolic disorders such as type-2 diabetes mellitus, hypertension, dyslipidemia, and obesity, which may be associated with variations in serum levels and poor delivery of certain mineral elements. METHODS: This study attempted to ascertain whether metabolic syndrome might be linked to alterations in serum levels of the mineral elements magnesium, copper, zinc, chromium, and nickel in a population of 92 diabetic subjects, some suffering from certain conditions associated with the metabolic syndrome, and 72 control subjects (Hospital Príncipe de Asturias, Alcalá de Henares, Spain). RESULTS: The results indicated that as a group the alterations implicated in metabolic syndrome were indeed associated with variations in blood levels of the mineral elements considered, though statistically significant differences were recorded only in the case of copper. Still, trends in mineral levels for each of the separate components contributing to the syndrome tended to increase. CONCLUSION: Metabolic complications appear to be associated with alterations in the levels of some minerals, especially copper.

[Probesci strategy: a cheaper therapeutic approach for obese patients]. / Estrategia probesci: un abordaje terapéutico de menor coste para el paciente obeso.

Obesity has become epidemic in Western countries. From clinical practice, obestity may be considered as a disease characterized by an excess of body fat mass, but patients usually demonstrate different responses to the same therapeutic strategy. It could be possible that the latter may be a consecuence of different pathophysiological factors among obese patients. Therefore, a detailed and thorough phenotyping of patients may enable clinitians to establish groups of patients that may respond in a homogeneous and effective way to a specific treatment for obesity. However, this type of approach can be especially time-consuming and may increase costs. In this study we describe the "PROBESCI" strategy, which is a novel system of studying the obese patient at the first visit, performed in groups of patients, aimed to the collection and analysis of data in order to categorize phenotypic profiles which may achive homogeneous responses to a specific therapy. We also analyze the costs of this new strategy compared to those of an individual consultation, showing a decrease of 58% for the first visit, and of 21% of the total costs throughout treatment.

Prevalence of hepatitis C virus genotypes in a Spanish liver transplant unit.

INTRODUCTION: Among the at least six major identified genotypes of HCV, genotype 1b, the one associated with a poorer prognosis, is the most prevalent in Spain. We aimed to compare the distribution of hepatitis C virus genotypes in our liver transplant unit with that of the other HCV patients at our institution (n = 413) in order to assess whether genotype 1b is more prevalent among patients with more severe liver disease. PATIENTS AND METHODS: One hundred eight patients of mean age 56 years included 81 (75%) OLT recipients and 27 (25%) with HCV cirrhosis. Determination of HCV genotypes was made with the Inno-LiPA HCV III. RESULTS: The overall distribution of genotypes was: 1b, 93 patients (86.1%); 1a; eight patients (7.4%); 3, four patients (3.7%); 4; two patients (1.9%), and 2; one patient (0.9%). The distribution was similar among patients with cirrhosis and OLT. Genotype 1b patients were older. Eleven (78.6%) of 14 patients with hepatocellular carcinoma had genotype 1b. In the control group the distribution was: 1b, 287 patients (69.5%); 1a, 54 patients (12.1%); 3, 41 patients (9.9%); 4, 20 patients (4.8%), and genotype 2, 11 patients (2.7%). This differences in the distribution of genotypes between our population and the control group was statistically significant (P < .001). CONCLUSIONS: Genotype 1b, the most prevalent genotype in our liver transplant unit, included older patients in whom hepatocellular carcinoma was common, perhaps due to their higher prevalence of cirrhosis.

Results of liver transplantation in patients with previous portosystemic shunts.

INTRODUCTION: Although liver transplantation is performed successfully in some patients with previous portosystemic shunts (PSS), these surgical procedures have been considered a relative contraindication for orthotopic liver transplantation (OLT). We aimed to determine whether a previous PSS worsens the prognosis of patients who undergo OLT. PATIENTS AND METHODS: Between March 1986 and October 2003, 520 liver transplants were performed in 467 patients in our center. Thirteen patients had undergone a PSS before OLT. The types of PSS were: portocaval (n = 8), splenorenal (n = 3), mesocaval (n = 1), and portoatrial (n = 1). We compared patients with previous PSS (cases) and the three patients with an OLT immediately before each case (controls). We analyzed the following variables: age, Child-Pugh stage, pretransplant liver disease, surgical times, transfusion requirements, infections, intensive care unit (ICU) stay, postoperative evolution, and survival. RESULTS: Age, Child-Pugh stage, and pretransplant liver disease were similar in both groups. There were no statistical differences in age, surgical times, ischemia time, anhepatic phase, transfusion requirements, ICU stay, infections, or hospital stay. The postoperative course was similar in both groups. Long-term survival was 84.62% in cases versus 78.5% in controls. CONCLUSIONS: Previous PSS should not be considered a contraindication for liver transplantation, even though this group of patients involves a special surgical challenge.

Effectiveness of pegylated interferon and ribavirin in patients with liver HCV cirrhosis.

Clearance of HCV before transplantation could avoid recurrence of hepatitis C in the liver allograft, thereby improving graft and patient survival. We report our experience with combined therapy for patients with HCV cirrhosis, including 12 patients with biopsy-proven liver cirrhosis (n = 7) or previous cirrhotic complications (n = 5). The Child-Pugh score was A in eight patients and B in four. Two patients had hepatocellular carcinoma. Genotype distribution was 1a (n = 2), 1b (n = 8) or 3 (n = 1). Patients received peginterferon alpha2b (1.5 microg/kg once weekly) and ribavirin (10.6 g/kg per day) for 48 weeks (genotype 1) or 24 weeks (genotype 3). Twenty-one months after beginning therapy all the patients remained alive; three have undergone liver transplantation. In one patient treatment was discontinued after 2 months due to cachexia. End-of-treatment virologic response was achieved in five patients (41.7%) and sustained virologic response in three patients (25%). Patients who cleared the virus had negative PCR 4 weeks after beginning therapy. All patients had adverse events. The most common clinical events were asthenia, weight loss, fever, and anorexia. Infectious complications resolved in three patients (25%). Hematologic events were common. Seven of 11 patients (63.6%) who completed therapy required dose reduction. We conclude that therapy with peginterferon and ribavirin in patients with HCV cirrhosis has a similar effectiveness to previous treatments. A virologic response 1 month after the beginning of therapy could be a main predictor of a sustained response.

Effect of short- and long-term experimental hyperthyroidism on plasma glucose level and insulin secretion during an intravenous glucose load and on insulin binding, insulin receptor kinase activity, and insulin action in adipose tissue.

Glucose disposal, insulin secretion, and insulin action in adipose tissue were measured in rats treated for 10 or 30 days with high doses of thyroxine (T4). Acutely induced hyperthyroidism produced a high rate of glucose disposal after an intravenous glucose tolerance test (IVGTT), accompanied by a high glucose-stimulated insulin secretion. In addition, in these rats the following phenomena were observed: (1) high insulin binding to isolated adipocytes due to an increase in the insulin receptor number; (2) high insulin binding to partially purified fat insulin receptors; (3) normal tyrosine kinase activity of fat insulin receptors; and (4) high insulin action in isolated adipocytes, such as glucose transport and lipogenesis. Chronically induced hyperthyroidism produced high rates of glucose disposal after an IVGTT, accompanied by an increase of basal and glucose-stimulated insulin secretion. These rats showed (1) normal insulin binding to either isolated adipocytes or partially purified insulin receptors; (2) normal tyrosine kinase activity of fat insulin receptors; (3) normal insulin action in isolated adipocytes. In conclusion, exogenous hyperthyroidism induced an increase in glucose disposal, probably due in part to high insulin secretion. In short-term T4-treated rats an additional increase of insulin action in adipocytes was also observed.

Histopathologic prognostic score in colorectal adenocarcinomas.

OBJECTIVE: To analyze the prognostic value of a set of pathological variables after curative resection for large bowel adenocarcinoma and to test a prognostic score derived from factors with independent effect. PATIENTS AND METHODS: The study is based on data from 292 consecutive unselected patients (B-C Astler-Coller stages). Histopathological features were evaluated prospectively on the resected primary tumors. Relationship between these factors and risk of recurrence was assessed by a Cox's proportional regression analysis. RESULTS: Four variables retained independent prognostic significance: extent of bowel wall invasion, peritumoral lymphocytic infiltration, number of positive nodes and vascular invasion. A prognostic score based on the regression coefficients attained by such variables was developed. This system revealed four prognostic groups. Group I included 14% of patients, with 94% 5-year disease-free survival. These figures were: 35% and 60% in group II; 43% and 46% in group III; and 7% and 24.4% in group IV. Histopathologic score applied to bearers of Astler-Coller B2 tumors permitted the identification of two populations, one characterized by a low risk of relapse and another with high risk (p = 0.002). CONCLUSION: A prognostic score based in the evaluation of four histopathologic parameters concerning the tumor phenotype enables the identification of groups of patients at risk of relapse after curative resection for colorectal adenocarcinoma.

Synthesis and theoretical study of 2-amino-2,3,3a,4,5,6-hexahydro-1H-phenalene and its biological evaluation on central dopaminergic system.

Compound 2 considered as a rigid non-hydroxylated 2-amino tetralin was synthesized and biologically evaluated. Central administration of compound 2 (50 microg or 100 microg/10 microl) induced a reduction in urinary sodium and potassium excretion at 3 and 6 h of urine collection. We speculate that compound 2 may be acting as a dopamine receptor antagonist.

[Body mass index influence in the insulin action mechanisms]. / Influencia del índice de masa corporal sobre los mecanismos de acción de la insulina.

OBJECTIVE: Improve the knowledge of the "in vitro" insulin action in healthy subjects with different body mass index (BMI), in order to know the role of obesity in the diabetes mellitus. MATERIAL: In 12 healthy subjects with different BMI and normal oral glucose test we made a gluteal biopsy to obtain adipose tissue. In the isolated adipocytes we studied the interaction of insulin with its receptor and the glucose transport. RESULTS: BMI was not correlated with the maximal specific 125I-insulin binding but was negative when correlated with the glucose transport in basal situation (r = -0.63, p < 0.05) as well as when stimulated with insulin (r = -0.67, p < 0.05), when the results were expressed as number of cells. When the data were expressed as surface, BMI was negative correlated with the percentage of maximal specific 125I-insulin binding (r = -0.81, p < 0.05), and also with the basal glucose transport (r = -0.69, p < 0.05) and stimulated with insulin (r = -0.77, p < 0.01). CONCLUSION: The increase of BMI is an important diabetogenic agent, acting at receptor as well as at postreceptor level, and the data should be expressed according to the cellular diameter rather than to the number of cells in subjects with different BMI. A cutting point was established at the 30 BMI level after which the described alterations could be observed.

[Short bowel syndrome cause of hypomagnesaemia importance of its diagnosis and treatment]. / Síndrome de intestino corto causa de hipomagnesemia, importancia de su diagnostico y tratamiento.

The short bowel syndrome (SIC) is a complex entity characterized by a malabsorptive state usually secondary to extensive intestinal resection originating a clinical, metabolic and/or nutritional disorder due to the reduction of the effective intestinal absorptive surface. The diagnosis is essentially clinical and, due to the patients malabsorptive process, it requires nutritional support to maintain their basic requirements, as the case reported. The clinical features of SIC patients depend on the grade of the alteration of function of the the small intestine or the impairment secondary to the surgical resection. We know that electrolytes are absorbed predominantly in the proximal gut. The regulation of ion/mineral levels depend on both the intestinal absorption and the renal excretion. We present an unusual case of SIC with only low absorption of magnesium. We discuss the most outstanding aspects of the case and review the literature.

El síndrome de intestino corto (SIC) es una entidad compleja caracterizada, por un estado malabsortivo secundario normalmente a una resección intestinal extensa que ocasiona alteraciones clínico, metabólicas y/o nutricionales debidas a la reducción de la superficie absortiva intestinal efectiva. El diagnóstico es fundamentalmente clínico y el paciente, por el proceso malabsortivo, requiere un soporte nutricional para mantener sus requerimientos básicos, como en el caso que presentamos. La clínica asociada al SIC también está en función de la zona de intestino delgado afectada por la resección o la alteración funcional. Sabemos que los electrolitos son absorbidos predominantemente en el intestino delgado. La regulación de los niveles de iones/minerales se basa tanto en la absorción intestinal como en la excreción renal. Consideramos de interés la publicación del caso, dado lo excepcional de la pérdida aislada de magnesio secundaria al SIC. Comentamos los aspectos más destacables del mismo y revisamos la literatura.