Laparoscopic adrenalectomy in children

Purpose: Reporting on the laparoscopic technique for adrenal disease in children and adolescents has been limited. We review here our experience with laparoscopic adrenal surgery in children. Patients and methods: 19 laparoscopic unilateral adrenalectomies were performed in 10 girls and 7 boys (mean age 3.9 years) during 1998-2011. The clinical diagnosis before surgery was virilizing tumor (n = 8), pheochromocytoma (n = 3), nonfunctioning solid adrenal tumor (n = 3), mixed adrenocortical tumor (n = 2), cystic adrenal mass (n = 1). Unilateral adrenal lesions were 20-65 mm at the longest axis on computerized tomography (12 right side, 7 left side). Results: The final clinicopathological diagnosis was cortical adenoma (n = 9), pheochromocytoma (n = 3, bilateral in two), neuroblastoma (n = 1), ganglioneuroblastoma (n = 1), ganglioneuroma (n = 1), adrenocortical carcinoma (n = 1), benign adrenal tissue (n = 1). Average operative time was 138.5 min (range 95-270). Blood transfusion was required in one case (5%). No conversion to open surgery was required and no deaths or postoperative complications occurred. Average hospital stay was 3.5 days (range 2-15). Average postoperative follow-up was 81 months (range 2-144). Two contralateral metachronic pheochromocytomas associated with von Hippel-Lindau syndrome occurred, treated with partial laparoscopic adrenalectomy (one without postoperative need of cortisone replacement therapy). Conclusions: Laparoscopic adrenalectomy is a feasible procedure that produces good results. It can be used safely to treat suspected benign and malignant adrenal masses in children with minimal morbidity and short hospital stay. (C) 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Progression to Adrenocortical Tumorigenesis in Mice and Humans through Insulin-Like Growth Factor 2 and beta-Catenin

Dysregulation of the WNT and insulin-like growth factor 2 (IGF2) signaling pathways has been implicated in sporadic and syndromic forms of adrenocortical carcinoma (ACC). Abnormal beta-catenin staining and CTNNB1 mutations are reported to be common in both adrenocortical adenoma and ACC, whereas elevated IGF2 expression is associated primarily with ACC. To better understand the contribution of these pathways in the tumorigenesis of ACC, we examined clinicopathological and molecular data and used mouse models. Evaluation of adrenal tumors from 118 adult patients demonstrated an increase in CTNNB1 mutations and abnormal beta-catenin accumulation in both adrenocortical adenoma and ACC. In ACC, these features were adversely associated with survival. Mice with stabilized beta-catenin exhibited a temporal progression of increased adrenocortical hyperplasia, with subsequent microscopic and macroscopic adenoma formation. Elevated Igf2 expression alone did not cause hyperplasia. With the combination of stabilized beta-catenin and elevated Igf2 expression, adrenal glands were larger, displayed earlier onset of hyperplasia, and developed more frequent macroscopic adenomas (as well as one carcinoma). Our results are consistent with a model in which dysregulation of one pathway may result in adrenal hyperplasia, but accumulation of a second or multiple alterations is necessary for tumorigenesis. (Ant J Pathol 2012, 181:1017-1033; http://dx.doi.org/10.1016/j.ajpath.2012.05.026)

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Inducible Nitric Oxide Synthase Inhibition Attenuates Physical Stress-Induced Lung Hyper-Responsiveness and Oxidative Stress in Animals with Lung Inflammation

Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2 alpha density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2a density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. copyright (C) 2012S. Karger AG, Basel

Retroperitoneoscopic adrenalectomy in pheochromocytoma

Since the first laparoscopic adrenalectomy, the technique has evolved and it has become the standard of care for many adrenal diseases, including pheochromocytoma. Two laparoscopic accesses to the adrenal have been developed: transperitoneal and retroperitoneal. Retroperitoneoscopic adrenalectomy may be recommended for the treatment of pheochromocytoma with the same peri-operative outcomes of the transperitoneal approach because it allows direct access to the adrenal glands without increasing the operative risks. Although technically more demanding than the transperitoneal approach, retroperitoneoscopy can shorten the mean operative time, which is critical for cases with pheochromocytoma where minimizing the potential for intra-operative hemodynamic changes is essential. Blood loss and the convalescence time can be also shortened by this approach. There is no absolute indication for either the transperitoneal or retroperitoneal approach; however, the latter procedure may be the best option for patients who have undergone previous abdominal surgery and obese patients. Also, retroperitoneoscopic adrenalectomy is a good alternative for treating cases with inherited pheochromocytomas, such as multiple endocrine neoplasia type 2A, in which the pheochromocytoma is highly prevalent and frequently occurs bilaterally.

Oral glands in dipsadine ""goo-eater"" snakes: Morphology and histochemistry of the infralabial glands in Atractus reticulatus, Dipsas indica, and Sibynomorphus mikanii

Although snake infralabial glands are generally constituted of mucous cells, among dipsadines, they are much more developed and predominantly serous in nature, possibly due to the peculiar feeding habits of some species of this group, the ""goo-eaters"", which feed on soft and viscous invertebrates. We compared the morphology and histochemistry of the infralabial glands of three goo-eater species of Southeast Brazil, Atractus reticulatus, Dipsas indica and Sibynomorphus mikanii. In A. reticulatus the glands are formed by mixed acini composed of mucous and seromucous cells and in D. indica, they are composed of mucous tubules and seromucous acini. In S. mikanii the glands are organized in seromucous acini; mucous cells are restricted to the gland anterior region and to the duct lining epithelium. Ultrastructurally, secretory granule electron density varies from low to moderate, depending on their mucous or seromucous nature. The results indicate a large morphological and histochemical variation in the infralabial glands, probably reflecting differences in the secretion chemical composition and in feeding specialization among the three species. The protein content in the secretory cells can be related with the presence of toxins that can be used in chemical prey immobilization or detaching of snails from their shells. (c) 2007 Elsevier Ltd. All rights reserved.

Mucocele of the Glands of Blandin-Nuhn After Lingual Frenectomy

Mucoceles are the most common lesions of the minor salivary glands and typically appear as a fluctuant, bluish, nontender, submucosal swelling with a normal overlying mucosa. Mucoceles of the glands of Blandin-Nuhn (in the anterior portion of the ventral surface of the tongue) have been considered to be uncommon. This article reports an unusual case of a large extravasation mucocele involving the ventral surface of the tongue, which appeared after a lingual frenectomy.

Characterization of a Novel Oral Glucocorticoid System and Its Possible Role in Disease

Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11 beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11 beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11 beta-HSD2 inhibitor 18 beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

Congenital Adrenal Hyperplasia Due to 21 Hydroxylase Deficiency: From Birth to Adulthood

The most frequent form of congenital adrenal hyperplasia (CAH) is steroid 21-hydroxylase deficiency, accounting for more than 90% of cases. Affected patients cannot synthesize cortisol efficiently. Thus the adrenal cortex is stimulated by corticotropin (ACTH) and overproduces cortisol precursors. Some precursors are diverted to sex hormone biosynthesis, causing signs of androgen excess including ambiguous genitalia in newborn females and rapid postnatal growth in both sexes. In the most severe "salt wasting" form of CAH (similar to 75% of severe or "classic" cases), concomitant aldosterone deficiency may lead to salt wasting with consequent failure to thrive, hypovolemia, and shock. Newborn screening minimizes delays in diagnosis, especially in males, and reduces morbidity and mortality from adrenal crises. CAH is a recessive disorder caused by mutations in the CYP21 (CYP21A2) gene, most of which arise from recombination between CYP21 and a nearby pseudogene, CYP21P (CYP21A1P). Phenotype is generally correlated with genotype. Classic CAH patients require chronic glucocorticoid treatment at the lowest dose that adequately suppresses adrenal androgens and maintains normal growth and weight gain, and most require mineralocorticoid (fludrocortisone). Transition of care of older patients to adult physicians should be planned in advance as a structured, ongoing process.

Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: Role of acute hypothalamic-pituitary-adrenal axis activation

Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 +/- 1 degrees C and 36 +/- 1 degrees C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 +/- 1 degrees C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P < 0.05). We did not find changes in the relative weights of the spleen, thymus, and bursa of Fabricius (P > 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

Evaluation of Adrenal Reserve in Children with Acute Lymphocytic Leukemia Treated with Prednisone or Dexamethasone

Background/Aims: The purpose of this study was to compare adrenal gland reserve in acute lymphocytic leukemia (ALL) patients 8 weeks after treatment with either prednisone (PRED) or dexamethasone (DEX) during the induction phase of therapy. Methods: A double-blind comparative study of patients treated with PRED and DEX was performed. Sixteen patients received PRED (40 mg/m(2)/day) and 13 patients received DEX (6 mg/m(2)/day), both for 28 days. A low-dose adrenocorticotropic hormone test (1.0 mu g/m(2), IV) was performed before and weekly for 8 weeks after abrupt cessation of glucocorticoid therapy. Sixteen children without ALL were used as controls to determine the cutoff peak cortisol level (14.2 mu g/dl). Results: Both groups (PRED and DEX) displayed similar mean peak cortisol levels before treatment and during the 8 weeks of evaluation (p = 0.652). No relationship was observed between the incidence of infection/stress and peak cortisol level within each group, nor was there a difference in the frequency of infection/stress between groups (p = 0.359). Although the patients presented variations in peak cortisol during the study period, no signs or symptoms of adrenal insufficiency were observed. Conclusion: Patients who received PRED or DEX for 4 weeks showed similar adrenal reserves and infection rates for 8 weeks after abruptly stopping glucocorticoid therapy, suggesting that DEX, which is a better antileukemic drug than PRED, has similar adrenal suppression and recovery rates. Copyright (c) 2012 S. Karger AG, Basel

Oleoresin glands in copaiba (Copaifera trapezifolia Hayne: Leguminosae), a Brazilian rainforest tree

Although studies have addressed the chemical analysis and the biological activity of oleoresin in species of Copaifera, the cellular mechanisms of oleoresin production, storage, and release have rarely been investigated. This study detailed the distribution, ontogeny, and ultrastructure of secretory cavities and canals distributed in leaf and stem, respectively, of Copaifera trapezifolia, a Brazilian species included in a plant group of great economic interest. Axillary vegetative buds, leaflets, and portions of stem in primary and secondary growth were collected and processed in order to study the anatomy, histolocalization of substances, and ultrastructure. Secretory cavities are observed in the foliar blade and secretory canals in the petiolule and stem. They are made up of a uniseriate epithelium delimiting an isodiametric or elongated lumen. Biseriate epithelium is rarely observed and is a novelty for Leguminosae. Cavities and canals originate from ground meristem cells and the lumen is formed by schizogenesis. The content of the cavities and canals of both stem and leaf is oily and resinous, which suggests that the oleoresin could be extracted from the leaf instead of the stem. Phenolic compounds are also detected in the epithelial cell cytoplasm. Cavities and canals in the beginning of developmental stages have polarized epithelial cells. The cytoplasm is rich in smooth and rough endoplasmic reticula connected to vesicles or plastids. Smooth and rough endoplasmic reticulum and plastids were found to be predominant in the epithelial cells of the secretory cavities and canals of C. trapezifolia. Such features testify the quantities of oleoresin found in the lumen and phenolic compounds in the epithelial cell cytoplasm of these glands. Other studies employing techniques such as correlative light electron microscopy could show the vesicle traffic and the compartmentalization of the produced substances in such glands.

Oestrogen receptor beta in adenoid cystic carcinoma of salivary glands

Aims: This study aimed to describe the expression of oestrogen receptor (ER)alpha, ER beta and aromatase in salivary gland adenoid cystic carcinoma (ACC). Methods and results: ER alpha, ER beta and aromatase expression was analysed by immunohistochemistry in tissue microarray blocks from 38 cases of ACC and seven normal salivary glands. The intracellular localization and amount of total protein expression were investigated by immunofluorescence and western blotting in an ACC cell line. Western blotting analysis showed overexpression of ER alpha, ER beta and aromatase in the ACC cell line; however, with immunofluorescence, only ER beta was shown to be expressed in the nucleus. Immunohistochemistry revealed positive nuclear expression of ER beta, positive cytoplasmic expression of aromatase and a lack of ER alpha expression as compared with normal salivary glands. Conclusions: The nuclear expression of ER beta indicates that oestrogen may be active in ACC and possibly able to mediate E2-targeted gene transcription. This study strongly suggests that ER beta may be involved in tumour progression, playing a role in tumour development, and thus corroborating the indication for ER antagonists in the clinical control of ACC. This study opens a new perspective on the potential use of anti-oestrogens and aromatase inhibitors as therapeutic agents against ACC.

Supernumerary parathyroid glands in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Objective: To evaluate frequency, anatomic presentation, and quantities of supernumerary parathyroids glands in patients with primary hyperparathyroidism (HPT1) associated with multiple endocrine neoplasia type 1 (MEN1), as well as the importance of thymectomy, and the benefits of localizing examinations for those glands. Methods: Forty-one patients with hyperparathyroidism associated with MEN1 who underwent parathyroidectomy between 1997 and 2007 were retrospectively studied. The location and number of supernumerary parathyroids were reviewed, as well as whether cervical ultrasound and parathyroid SESTAMIBI scan (MIBI) were useful diagnostic tools. Results: In five patients (12.2%) a supernumerary gland was identified. In three of these cases (40%), the glands were near the thyroid gland and were found during the procedure. None of the imaging examinations were able to detect supernumerary parathyroids. In one case, only the pathologic examination could find a microscopic fifth gland in the thymus. In the last case, the supernumerary gland was resected through a sternotomy after a recurrence of hyperparathyroidism, ten years after the initial four-gland parathyroidectomy without thymectomy. MIBI was capable of detecting this gland, but only in the recurrent setting. Cervical ultrasound did not detect any supernumerary glands. Conclusion: The frequency of supernumerary parathyroid gland in the HPT1/MEN1 patients studied (12.2%) was significant. Surgeons should be aware of the need to search for supernumerary glands during neck exploration, besides the thymus. Imaging examinations were not useful in the pre-surgical location of these glands, and one case presented a recurrence of hyperparathyroidism.

Baroreceptor-mediated activation of sympathetic nerve activity to salivary glands

Salivary gland function is regulated by both the sympathetic and parasympathetic nervous systems. Previously we showed that the basal sympathetic outflow to the salivary glands (SNA(SG)) was higher in hypertensive compared to normotensive rats and that diabetes reduced SNA(SG) discharge at both strains. In the present study we sought to investigate how SNA(SG) might be modulated by acute changes in the arterial pressure and whether baroreceptors play a functional role upon this modulation. To this end, we measured blood pressure and SNA(SG) discharge in Wistar-Kyoto rats (WRY-intact) and in WRY submitted to sinoaortic denervation (WRY-SAD). We made the following three major observations: (i) in WRY-intact rats, baroreceptor loading in response to intravenous infusion of the phenylephrine evoked an increase in SNA(SG) spike frequency (81%, p<0.01) accompanying the increase mean arterial pressure ((sic)MAP: +77 +/- 14 mmHg); (ii) baroreceptor unloading with sodium nitroprusside infusion elicited a decrease in SNA(SG) spike frequency (17%, p<0.01) in parallel with the fall in arterial blood pressure ((sic)MAP: 30 3 mmHg) in WRY-intact rats; iii) in the WRY-SAD rats, phenylephrine-evoked rises in the arterial pressure ((sic)MAP: +56 +/- 6 mmHg) failed to produce significant changes in the SNA(SG) spike frequency. Taken together, these data show that SNA(SG) increases in parallel with pharmacological-induced pressor response in a baroreceptor dependent way in anaesthetised rats. Considering the key role of SNA(SG) in salivary secretion, this mechanism, which differs from the classic cardiac baroreflex feedback loop, strongly suggests that baroreceptor signalling plays a decisive role in the regulation of salivary gland function. (C) 2012 Elsevier Inc. All rights reserved.