Novel pathogenic variant of DICER1 in an adolescent with multinodular goiter, ovarian Sertoli-Leydig cell tumor and pineal parenchymal tumor of intermediate differentiation.

OBJECTIVES: To present a case of a new pathogenic variant of DICER1. CASE PRESENTATION: 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli-Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. CONCLUSIONS: Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.

One-Shot Drilling Analysis of Stack CFRP/UNS A92024 Bonding by Adhesive.

The use of adhesive layers can improve the properties and reduce the defects produced in the interfaces. This provides adherence to the structure, adapting the joining surfaces and avoiding spaces between the layers. However, the presence of the adhesive can potentiate the defects caused during drilling. In turn, a loss of adhesive in the interface can occur during machining affecting the final structure. This work has followed a conventional OSD strategy in CFRP and UNS A92024 aluminium sheet stacking with adhesive. A series of dry drilling tests have been developed with different cutting conditions and new noncoated WC-Co helical cutting tools. Analysis of Variance (ANOVA) statistical analyses and surface response models have been applied to determine the mechanical behaviour in the holes. For this purpose, the dimensional deviation, surface quality, and adhesive loss in the interface in relation to the number of holes have been considered. A combination of cutting parameters that minimizes the evaluated defects has been found. Diametric deviations and surface qualities below 2% and 3.5 µm have been measured in the materials that make up the stack with cutting speeds higher than 140 m/min and feed rates between 200 and 250 mm/min. However, the greatest adhesive losses occur at high cutting speeds.

Tool Wear Mechanism in Cutting of Stack CFRP/UNS A97075.

The aeronautics industry's competitiveness has led to the need to increase productivity with one shot drilling (OSD) systems capable of drilling stacks of dissimilar materials (fibre/metal laminates, FML) in order to reduce riveting times. Among the materials that constitute the current aeronautical models, composite materials and aluminium (Al) and titanium (Ti) alloys stand out. These one-pass machining techniques produce high-quality holes, especially when all the elements that have to be joined are made of the same material. This work has followed a conventional OSD strategy and the same cutting conditions applied to CFRP (carbo-fibre-reinforced polymer), Al and CFRP/Al stacked sheets to know the wear mechanisms produced. With this purpose, results were obtained by using current specific techniques, such as microstructural analysis, monitoring of the shear forces and analysis of macrogeometric deviations. It has been determined that when these drilling techniques are applied under the same cutting conditions to stacks of materials of a different nature, the results of the wear mechanisms acting on the tool differ from those obtained when machining each material separately. This article presents a comparison between the effects of tool wear during dry drilling of CFRP and UNS A97075 plates separately and when machined as stacks.

Anatomía de la vía aérea para el broncoscopista. Una aproximación a la anestesia / Airway anatomy for the bronchoscopist: An anesthesia approach

Introducción: El conocimiento y desarrollo de habilidades en el manejo de la vía aérea es una de las competencias importantes en la formación del anestesiólogo; el «saber¼ y el «saber hacer bien y rápido¼ son determinantes en algunas situaciones críticas a las que se puede enfrentar durante el manejo anestésico. La broncoscopia es un procedimiento útil tanto diagnóstico como terapéutico. El conocimiento de la técnica y de la anatomía de la vía aérea constituye el pilar de la broncoscopia, encontrando diferentes variaciones anatómicas y clasificaciones de la vía aérea. Objetivo: Describir la anatomía de la vía aérea a través de esquemas, evaluar variaciones anatómicas y conocer características propias del procedimiento. Metodología: Con las palabras clave «Bronchoscopy¼, «Anatomy¼, «Airway¼ y «Anesthesia¼ se realizó una revisión no sistemática en bases de datos (PUBMED/MEDLINE, Science Direct, OVID, SciELO). Resultados y conclusiones: La broncoscopia es un procedimiento útil en el plano quirúrgico y diagnóstico, siendo utilizado en distintos procedimientos. Las variaciones anatómicas de la vía aérea se presentan en un porcentaje pequeño de la población. Las clasificaciones anatómicas son diversas tanto anatómica como numéricamente; sin embargo, lo relevante es desarrollar una relación espacial. La broncoscopia es una técnica que va en desarrollo paralelo a otros avances de la tecnología biomédica, es un procedimiento del cual el anestesiólogo debe investigar más con el fin de generar mejores efectos en el campo de la anestesiología.

Introduction: Knowledge and development of skills in the management of the airway is one of important competencies in the training of the anesthesiologist, "knowledge" and "know how well and fast" are decisive in some critical situations during the anesthetic management. Bronchoscopy is a useful both diagnostic and therapeutic procedure. Knowledge of technique and the anatomy of the airway is the key of bronchoscopy, finding different anatomic variations and classifications of the airway. Objective: Describe the airway anatomy through diagrams, evaluate anatomic variations and characteristics of procedure. Methodology: With the keywords "Bronchoscopy" and "Anatomy", "Airway", "Anesthesia" held a non-systematic review databases (PUBMED/MEDLINE, OVID, Science Direct, SciELO). Results and conclusions: The bronchoscopy is a useful procedure in the surgical level and diagnosis, being used in various procedures. Airway anatomical variations occur in a small percentage of the population. Anatomical classifications are different both anatomic as numerically, but what is important is developing a spatial relation. Bronchoscopy is a technique that goes in parallel development of other advances in biomedical technology, is a procedure whereby the anesthesiologist should be investigated in order to generate better effects in the field of the anesthesiology.

Diferencias de sexo en el dolor. Una aproximación a la clínica / Pain and gender differences. A clinical approach

Introducción: El dolor en la clínica sigue siendo una de las mayores causas de consulta en centros clínicos, por lo tanto comprender las diferencias de sexo en cuanto al dolor se refiere es importante y trascendental para el manejo clínico del paciente en los diferentes servicios. La presentación del dolor en pacientes de diferente sexo suele tratarse de la misma manera, aunque son varios los factores involucrados en el manejo del dolor en relación al sexo que algunas veces no son tenidos en cuenta en la práctica clínica. Objetivo:Describir las diferencias entre hombre y mujer en relación al dolor, desde distintos aspectos tales como factores anatómicos, fisiológicos, neurales, hormonales, psicológicos y socioculturales en la práctica anestésica. Metodología: Con las palabras clave se realizó una revisión no sistemática en bases de datos (Pubmed/Medline, Science Direct, OVID, SciElo). Resultados y conclusiones: Las diferencias entre hombre y mujer respecto al dolor involucran factores anatómicos, fisiológicos, neurales, hormonales, psicológicos y socioculturales. Al evaluar estos factores se concluye que la mujer reporta con mayor frecuencia dolor y presenta un umbral más bajo de dolor que los hombres, refiriendo más dolor musculoes-quelético, neuropático, por electricidad y por presiones de temperatura. Aun así, responde mejor a los opioides, en especial el receptor κ.

Introduction: Pain continues to be one of the most frequent complaints in clinical centers. Pain Consequently, understanding gender differences in relation to pain is important and critical for the clinical management of patients by the different healthcare services. Pain in patients of different gender is usually treated in the same way; however, there are several gender-associated factors involved in the management of pain, which sometimes are not taken into consideration in clinical practice. Objective: To describe the differences between men and women as far as pain is concerned, taking into consideration anatomical, physiological, neural, hormonal, psychological, social and cultural factors in the practice of anesthesia. Methodology: A non-systematic review was undertaken using the key words in the Pubmed/Medline, Science Direct, OVID, SciElo data bases. Results and conclusions: Differences between men and women when it comes to pain involve anatomical, physiological, neural, hormonal, psychological, social and cultural factors. When examining those factors, it is found that women report pain more frequently, and have a lower threshold for pain than men. They usually complain more of muscle-skeletal, neuropathic, electrical shock and temperature-related pain, but respond better to opioids, in particular κ receptor-binding opioids.

Infección congénita por citomegalovirus en recién nacidos del estado de San Luis Potosí, México / Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosí, Mexico

OBJETIVO: Determinar la prevalencia de infección congénita por citomegalovirus en recién nacidos participantes en el programa de tamiz neonatal de los Servicios de Salud de San Luis Potosí. MATERIAL Y MÉTODOS: Se evaluó la presencia de citomegalovirus en muestras de sangre almacenadas en papel filtro. RESULTADOS. Se detectó la presencia de citomegalovirus en 10 (0.68 por ciento) de 1 457 muestras estudiadas. No se encontraron diferencias en las características de los recién nacidos con infección congénita en comparación con aquéllos sin infección. CONCLUSIONES: Es necesario concientizar a los profesionales de la salud sobre la prevalencia e impacto de la infección congénita por citomegalovirus.

OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí. MATERIAL AND METHODS: We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. RESULTS: Cytomegalovirus was detected in 10 (0.68 percent) of the 1 457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. CONCLUSIONS: It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.

[Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosí, Mexico]. / Infección congénita por citomegalovirus en recién nacidos del estado de San Luis Potosí, México.

OBJECTIVE: To determine the prevalence of congenital cytomegalovirus infection in newborn infants included in the neonatal screening program coordinated by the State Health Services in San Luis Potosí. MATERIAL AND METHODS: We evaluated the presence of cytomegalovirus in blood samples stored in filter paper. RESULTS: Cytomegalovirus was detected in 10 (0.68%) of the 1,457 samples included in the study. There were no differences in the characteristics of infants with congenital infection compared to those without infection. CONCLUSIONS: It is necessary to increase awareness of health professionals regarding the prevalence and impact of congenital cytomegalovirus infection.

Effect of estrogen on the blood supply of pituitary autografts in rats.

Estrogens are known to cause pituitary enlargement and lactotroph proliferation. They also modulate pituitary angiogenesis and induce tumor formation. Pituitary grafts, due to the loss of hypothalamic dopamine, also show lactotroph hyperplasia. We investigated the role of estrogen on rat pituitary autograft vascularization by light and transmission electron microscopy, and assessed prolactin (PRL) blood levels, microvessel density (MVD) and cell proliferation using the BrdU labeling index. All adenohypophysial cell types were identified by immunohistochemistry (streptavidin-biotin-peroxidase complex method). The proangiogenic factors, vascular endothelial growth factor (VEGF), its receptor Flk-1, and hypoxia inducible factor-1alpha (HIF-1alpha) were similarly demonstrated. The prevalence of lactotrophs, as well as more intense staining for VEGF, Flk-1 and HIF-1alpha, was noted in those grafts exposed to estrogen, mainly in the area surrounding the central necrotic core. Immunostaining showed Flk-1 expression increased in endothelial cells of the estrogen-exposed grafts as compared with those unexposed. In contrast to the grafts not exposed to estrogen, in the estrogen-exposed grafts, only fenestrated endothelium could be demonstrated, suggesting that estrogen induces fenestration of newly formed capillaries. There was an increase in blood PRL levels in the estrogen-treated groups as compared with controls. Both MVD and BrdU labeling indices were higher in grafts exposed to estrogen, especially after 4 weeks. Our results suggest that estrogen administration not only enhances the expression of proangiogenic factors in the pituitary grafts but also induces their expression at earlier stages, leading to rapid neoformation of purely fenestrated capillaries.

The spectrum of malignancy in craniopharyngioma.

Craniopharyngiomas are low-grade epithelial neoplasms occurring almost exclusively in the sellar/suprasellar region. Histologic malignancy is extremely rare; the literature consists mostly of isolated case reports. Herein, we report 3 patients with craniopharyngiomas exhibiting histologic malignancy, 2 of which received radiation therapy before its appearance. Hematoxylin and eosin-stained slides and selected immunohistochemical stains were reviewed in all cases. Microvessel density analysis was performed in case 2. The patients included 2 men and 1 woman, age 14, 31, and 58 years at presentation, respectively. All patients expired 3 months to 9 years after first resection and 3 to 9 months after identification of histologic malignancy. The latter developed after multiple recurrences and radiation therapy in 2 cases, but seemed to arise de novo in 1 case resembling odontogenic ghost cell carcinoma and lacking any definite low-grade craniopharyngioma precursor. The malignant component of the other 2 cases resembled squamous cell carcinoma and low-grade myoepithelial carcinoma, respectively. The MIB-1 labeling index was markedly increased in the malignant component in comparison with the low-grade precursor. Malignant transformation in craniopharyngiomas, although rare, does exist. It assumes varied histologic appearances, usually after multiple recurrences and radiation therapy, and has a near uniformly fatal outcome. De novo malignancy in odontogenic tumors of the sella is even more unusual, but also has an ominous prognosis.

Prolactin-like hormone in the nematode Trichinella spiralis larvae.

Expression of prolactin (PRL) or prolactin-like hormone has been reported in invertebrates. We investigated the larval phase of Trichinella spiralis: (a) to express 23 kDa PRL, (b) to define its localization and (c) to test its possible biological activity. Immunostaining in isolated larvae demonstrated positive material to 23 kDa PRL by all along the stichosome, specifically in the stichocytes. Homogenized immunoblot larvae showed a 23 kDa protein band. To assess PRL release and its biological activity, larvae were incubated in culture medium and the excretory/secretory products were analyzed by the Nb2 cells bioassay. A cellular growth equivalent until 10 nM PRL and using antibody against 23 kDa PRL, the growth was blocked. In conclusion our result provides evidence that PRL-like hormone is expressed and secreted by the larvae of T. spiralis.

Insulin-like growth factor (IGF)-I controls prostate fibromuscular development: IGF-I inhibition prevents both fibromuscular and glandular development in eugonadal mice.

Although antiandrogen therapy has been shown effective in treating prostatic tumors, it is relatively ineffective in treating benign prostatic hyperplasia (BPH). In an attempt to understand better the role of androgens in the development of the normal prostate and BPH, we studied the relative effects of testosterone and IGF-I on the development of the two compartments of the prostate in castrated IGF-I((-/-)) male mice. Here we report that IGF-I stimulated the development of the fibromuscular compartment, but testosterone inhibited it (stromal epithelial ratio 2.17 vs. 0.83, respectively; P < 0.001). Testosterone also impaired IGF-I induced insulin receptor substrate-1 phosphorylation and cell division, and increased apoptosis in fibromuscular tissue. In sharp contrast IGF-I and testosterone both stimulated the development of the glandular compartment individually and together. The combined effects were either additive or synergistic on compartment size, cell division, insulin receptor substrate-1 phosphorylation, and probasin production. Together they also had a greater inhibitory effect on apoptosis in gland tissue. To determine whether IGF-I inhibition would inhibit both fibromuscular and glandular compartments, we tested the effect of IGF binding protein-1 on prostate development in two different models: castrated Ames dwarf mice and eugonadal normal male mice. IGF binding protein-1 blocked bovine GH-induced fibromuscular and glandular development in both. It also inhibited epithelial cell division and increased apoptosis in both prostate compartments in the eugonadal mice. The observed discordance between IGF-I and testosterone control of prostate compartment development might explain the relative failure of 5alpha-reductase inhibition in BPH and why testosterone inhibition might theoretically reduce gland volume but increase fibromuscular tissue. The work also provides a rationale for considering IGF-I inhibition as therapy for BPH to reduce the size of both prostate compartments.

Modulation of VEGF/Flk-1 receptor expression in the rat pituitary GH3 cell line by growth factors.

Both vascular endothelial growth factor (VEGF) and its receptor Flk-1 are expressed in normal pituitary cells and in the prolactin- and growth hormone-producing GH3 cell line of the rat, thus suggesting autocrine/paracrine function. Regulation of the Flk-1 receptor system in pituitary cells is poorly understood, but evidence suggests that up-regulated growth factors play a role in its expression and activation. To study the role of growth factors in this process, we examined changes in VEGF and Flk-1 expression in GH3 cells following varied exposure to betaFGF, EGF, and TGFbeta1. Immunofluorescence labelling and laser scanning cytometry were used to measure changes in VEGF and Flk-1 expression. Results showed that betaFGF, EGF and TGFbeta up-regulated the VEGF/FLK-1 receptor system. Distinct patterns of activation were detected. At 2 hours, EGF and TGFbeta caused no significant changes in VEGF and Flk-1 expression; however, betaFGF up-regulated VEGF expression in 99% of cells but only induced modest changes in Flk-1 overexpression. A similar percentage of cells overexpressed VEGF after 24-hour incubation with betaFGF, but more prominent Flk-1 overexpression was detected. At 24 hours, EGF and TGFbeta1 induced a significant increase in both VEGF and Flk-1 expression. In summary, our findings show that VEGF/Flk-1 expression in pituitary cells may be altered by different growth factors. This may affect angiogenesis and the progression of pituitary tumors.

Vascularization of rat pituitary autografts.

Pituitary autotransplantation eliminates direct vascular contact between the hypothalamus and the adenohypophysis, and enables us to study the role of the hypothalamus in regulating adenohypophysial endocrine activity. The aim of this study was to investigate vascularization of the pituitary autografts. Three-month-old male Wistar rats were hypophysectomized, and their adenohypophyses were autotransplanted under the renal capsule. The animals were killed 3 weeks after autotransplantation. The grafts were removed and studied by using histology, immunohistochemistry and transmission electron microscopy. In the central portion of the grafts, organizing necrosis was apparent. The peripheral portion of the graft contained all adenohypophysial cell types, with a predominance of lactotrophs. Vascular endothelial growth factor and hypoxia-inducible factor were expressed in the graft mainly in the perinecrotic areas. Several capillaries inside the grafts were lined by continuous unfenestrated epithelium, while others were lined by fenestrated endothelium, suggesting that neovascularization is the result of two processes: ingrowths of capillaries from the renal capsule to the graft, and neoformation of capillaries from pre-existing adenohypophysial vessels. In conclusion, hypoxia seems to be an important factor in the vascularization of pituitary autografts. Mediated via hypoxia-inducible factor, hypoxia stimulates vascular endothelial growth factor secretion, which plays a crucial role in angiogenesis.

Angiogenesis and the growth potential of craniopharyngiomas.

The present study was performed to evaluate the role of neovascularization on the behavior of craniopharyngiomas as well as the contribution of endothelial cell proliferation and migration in the remodeling and expansion of the vascular network associated with angiogenesis. Fourteen primary tumors were studied, all of the adamantinomatous type. CD34 immunostaining, an endothelial cell marker, localized vessels within the connective tissue stroma. MIB-1 immunopositivity was apparent in the nuclei of neoplastic cells, few endothelial cells, and stromal elements. MIB-1 counts were higher in epithelial than connective tissue cells. A positive correlation was found between the number of MIB-1 immunopositive cells and microvessel density (MVD). Immunohistochemistry demonstrated that integrin alphavbeta3 expression was restricted to tumor vasculature; the tumor cells were immunonegative. Only 2.5% of vessels detected with CD34 were immunopositive for integrin alphavbeta3. At present, no therapeutic implications can be drawn from our observations. More studies are needed to assess whether integrin alphavbeta3 antagonists or drugs that arrest the cell cycle of endothelial cells can inhibit angiogenesis in craniopharyngiomas.

Analysis of epidermal growth factor receptor and activated epidermal growth factor receptor expression in pituitary adenomas and carcinomas.

Epidermal growth factor receptor plays an important role in the pathogenesis of many malignancies. Various growth factors, including epidermal growth factor receptor, have been shown to influence pituitary tumor growth and differentiation. To analyze the role of epidermal growth factor receptor in pituitary tumor development, we examined normal pituitaries (n=8), pituitary adenomas (n=158), and pituitary carcinomas (n=7) for expression of epidermal growth factor receptor protein and messenger RNA using tissue microarrays and RT-PCR. We also examined (a) the expression of phospho-epidermal growth factor receptor, the activated form of epidermal growth factor receptor, in pituitary tumors and normal pituitaries by immunohistochemistry and (b) the effects on epidermal growth factor receptor expression of treating pituitary cells (HP75 cell line) with epidermal growth factor. Epidermal growth factor receptor and the phosphorylated variant expression were present in normal pituitary cells. Epidermal growth factor receptor messenger RNA was also detected in normal pituitaries, pituitary adenomas, and carcinomas by in situ hybridization and RT-PCR. Most pituitary adenomas showed expression of epidermal growth factor receptor and the phosphorylated variant. Nonfunctional adenomas showed higher levels of expression of epidermal growth factor receptor (76 vs 34%) and of phospho-epidermal growth factor receptor (26 vs 8%) as compared to functional adenomas. Five of seven pituitary carcinomas showed strong expression of both epidermal growth factor receptor and phospho-epidermal growth factor receptor. When a human pituitary cell line (HP75) was cultured in the presence of epidermal growth factor receptor, there was an increase in the levels of both epidermal growth factor receptor and phospho-epidermal growth factor receptor after 5 h of treatment, thus confirming that epidermal growth factor receptor signaling was active in pituitary tumors. These results indicate that activated epidermal growth factor receptor is expressed in pituitary adenomas and carcinomas. Higher levels in pituitary carcinomas suggest a role in pituitary tumor progression.

Analysis of Cox-2 and thromboxane synthase expression in pituitary adenomas and carcinomas.

Recent studies have examined the role of cyclooxygenase-2 (Cox-2) expression in normal pituitaries and pituitary adenomas and have suggested a role for Cox-2 in the regulation of angiogenesis in the pituitary. Thromboxane synthase (TBXAS), which catalyzes the synthesis of thromboxane A2, is one of the downstream enzymes in Cox metabolism and appears to play a role in the regulation of invasiveness and angiogenesis in some neoplasms. To analyze the role of Cox-2 and TBXAS in pituitary tumor progression, we examined normal pituitaries (n = 8), pituitary adenomas (n = 174), and pituitary carcinomas (n = 7) for expression of Cox-2 and TBXAS by immunohistochemistry. Weak Cox-2 and moderate TBXAS expression was present in normal pituitary cells. Most pituitary adenomas showed increased expression of both Cox-2 and TBXAS. Pituitary tumors as a whole, but particularly carcinomas, showed greater Cox-2 expression than did normal pituitaries. Pituitary adenomas and carcinomas also showed greater staining for TBXAS when compared to normal pituitary. Nonfunctional adenomas had significantly higher levels of TBXAS expression compared to functional adenomas (p = 0.017). Adenomas and carcinomas showed similar degrees of staining for TBXAS. In summary, TBXAS appears to be one of the up-regulated downstream enzymes of Cox metabolism in pituitary tumors. Both Cox-2 and TBXAS may play an important role in pituitary tumor development and progression.

Cox-2 expression in the oxyphilic cells of the normal, hyperplastic, and adenomatous parathyroid gland.

We investigated cyclooxygenase expression in parathyroid glands from patients with various pathological conditions in order to coordinate levels of immunoreactivity with histology, with preoperative serum levels of calcium, phosphate, and intact parathyroid hormone, and with clinical diagnoses. Surgical specimens were obtained from 38 patients diagnosed with adenoma and primary, secondary, and tertiary hyperplasias. Incidentally removed parathyroids served as controls. After routine histological processing, approximations of total area and area of oncocytic nodules were calculated for each section of gland. Immunohistochemical reactivities for Cox-1, Cox-2, and values for integrated Cox-2 reactivity were quantified and compared with the clinical diagnoses and preoperative serum biochemistry. For the pooled cases, serum phosphate and PTH were directly related to each other, to total glandular area, and to integrated oncocytic area. Serum calcium was inversely related to serum phosphate and PTH levels as well as to total gland size. Within the adenoma group, the pure chief cell adenoma patients were younger and their tumors showed greater proliferative activity than those in the oncocytic adenoma group. For secondary and tertiary hyperplasias, the number of oncocytic nodules was significantly higher than in the adenomas and primary hyperplasias. In our study, the oncocytic cells are the only demonstrable site of Cox activity. It is suggested that the oncocytic cells play a role in prostaglandin metabolism within the parathyroids and may have a role in the regulation of PTH secretion.

Effect of gamma knife radiosurgery on a pituitary gonadotroph adenoma: a histologic, immunohistochemical and electron microscopic study.

The morphologic findings in a pituitary macroadenoma removed from a 65-year old man by the transsphenoidal approach 9 months after gamma knife surgery are reported. The tumor was immunoreactive for FSH beta and showed ultrastractural features consistent with an oncocytic gonadotroph adenoma. Accumulation of connective tissue separating small groups of adenoma cells was evident. Several dilated vessels and numerous vascular endothelial growth factor immunopositive adenoma cell were noted. By electron microscopy the endothelial linings frequently showed discontinuities with platelet accumulation attached to the gaps. Several vessels were severely injured showing necrosis of endothelial cells. It can be concluded that gamma knife surgery caused severe alterations in pituitary adenoma microcirculation indicating that vascular injury plays a crucial role in tumor shrinkage.

Immunohistochemical localization of amylin in human pancreas, thyroid, pituitary and their tumors.

The aim of the present study was to investigate immunohistochemically expression of amylin, a 37 amino acid peptide, cosecreted with insulin by beta cells in pancreatic islets in 12 non-tumorous pancreatic tissues, 22 pancreatic islet tumors, 14 non-tumorous thyroids, 14 medullary carcinomas of the thyroid, 10 non-tumorous pituitaries and 50 pituitary adenomas including 10 amyloid-forming prolactin-cell adenomas using the streptavidin-biotin-peroxidase complex method. Amylin was expressed in non-tumorous pancreatic islets but not in non-tumorous thyroids and pituitaries. Since amylin plays an important role in amyloid formation in pancreatic islets, those tumor types were selected to study which may produce amyloid. Amylin was widely expressed in one insulin producing beta cell tumor. Few tumor cells were immunopositive in 8 islet-cell tumors and in 5 medullary thyroid carcinomas. Immunostaining was not found in pituitary adenomas, including those which produced amyloid. It can be concluded that amylin is not a satisfactory immunohistochemical marker to identify pancreatic islet tumors, medullary thyroid carcinomas and pituitary adenomas.

Microvascular structural entropy: a novel approach to assess angiogenesis in pituitary tumors.

Entropy, a measure of the degree of disorder in a system, has recently been used in different morphologic studies to quantify regularity. Our aims were (a) to study the structural organization of the microvascular bed in prolactin (PRL)-producing adenomas and carcinomas, the most vascularized of pituitary tumors, by assessing microvascular structural entropy (MSE), and (b) to determine whether the degree of disorder of the capillary bed correlates with tumor cell proliferation as estimated by MIB-1 labeling, microvessel density (MVD), the most widely used method of quantifying blood vessel formation, and various clinicopathologic parameters (gender, age, tumor size and invasiveness). The morphometric study demonstrated statistically significant differences in MIB-1 labeling, MVD, and MSE between PRL-producing adenomas and carcinomas. Unlike MIB-1 labeling index (PRL-producing adenomas 1.5 +/- 0.27; carcinomas 15.0 +/- 4.04) and MVD (PRL-producing adenomas 2.7 +/- 0.34; carcinomas 4.2 +/- 0.72), the MSE values were significantly higher in adenomas (171.5 +/- 25.37) than in carcinomas (67.9 +/- 17.45). These results indicate that PRL-producing carcinomas have a less chaotic distribution of vessels than benign adenomas. In contrast to a lack of correlation between microvessel density and other morphometric parameters, a strong negative correlation was found between MSE and MIB-1 labeling index (r = 0.511, p = 0.003). It thus appears that regular, less chaotic microvascular geometry contributes to increased proliferative activity in PRL cell tumors. Analysis of MSE may provide an independent parameter of tumor behavior, and contributes to a better understanding of the role of microvasculature in pituitary tumor progression.